Defending Drug and Medical Device Litigation: A Primer for

Transcription

Defending Drug and
Medical Device Litigation:
A Primer for Young Lawyers
Primer Materials
September 2014
All views, opinions and conclusions expressed
are those of the authors and/or speakers, and
do not necessarily reflect the opinion and/or
policy of DRI and its leadership.
© 2014 by DRI
55 West Monroe Street, Suite 2000
Chicago, Illinois 60603
All rights reserved. No part of this product may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying and recording, or by any information storage or retrieval system,
without the express written permission of DRI unless such copying is expressly permitted by federal copyright law.
Produced in the United States of America
Primer Materials Table of Contents
FDA Regulation of Drugs and Medical Devices......................................................................................... 1
W. Kennedy Simpson
Products Liability:...................................................................................................................................... 13
Claims, Defenses, and Case Handling
Edward W. Gerecke and David J. Walz
Defending Failure-To-Warn Claims.......................................................................................................... 51
Maja C. Eaton
Medical Causation and Epidemiologic Issues......................................................................................... 117
Bruce R. Parker
Discovery Issues........................................................................................................................................ 149
Kimberly D. Baker
Potential Pitfalls of FRCP 30(b) (6) and 30(b) (1) in Drug & Device Litigation.................................. 167
N. Karen Deming
Daubert—Practical Approach to Understanding Daubert and Challenging Expert Opinions........... 189
Mary Nold Larimore
Some Perspectives From Our Clients...................................................................................................... 201
Stacey Dixon Calahan
FDA Regulation of Drugs
and Medical Devices
W. Kennedy Simpson
Thompson Miller & Simpson
734 West Main Street, Suite 400
Louisville, KY 40202
(502) 357-1923
(502) 585-9993 [fax]
[email protected]
www.tmslawplc.com
W. Kennedy Simpson is a founding member of Thompson Miller & Simpson PLC
in Louisville, Kentucky. Mr. Simpson has been involved in the defense of product
liability and medical malpractice cases for more than 25 years. He has tried more
than 100 cases to verdict in nine different states. Mr. Simpson has been involved in
many appellate decisions relating to significant Kentucky product liability law issues.
He is a member of PLAC, IADC, ABOTA and DRI (where he has served on the
steering committee of the Drug and Medical Device Committee).
FDA Regulation of Drugs and Medical Devices
Table of Contents
I. Presentation Outline.......................................................................................................................................5
II. Overview of FDA Regulatory Process: Drugs and Medical Devices............................................................6
A.Drugs........................................................................................................................................................6
B. Medical Devices.......................................................................................................................................9
III.Bibliography..................................................................................................................................................11
IV.Websites.........................................................................................................................................................12
FDA Regulation of Drugs and Medical Devices ■ Simpson ■ 3
FDA Regulation of Drugs and Medical Devices
I. Presentation Outline
• OVERVIEW OF APPROVAL PROCESS
•RESEARCH
•DRUGS
IND
•DEVICES
IDE
•APPROVAL
• DRUGS NDA
• SAFETY & EFFICACY
• SUBSTANTIAL EVIDENCE
• ADEQUATE & WELL-CONTROLLED STUDIES
•DEVICES
•CLASSES
• PMA APPROVAL
• SAFETY & EFFICACY
• REASONABLE ASSURANCE
• VALID SCIENTIFIC EVIDENCE
• 510k CLEARANCE
• SUBSTANTIAL EQUIVALENCE
•PREEMPTION
•MARKETING
•MANUFACTURING
•cGMP
•LABELING
• PACKAGE INSERT
• OFF-LABEL USE
•ADVERTISING
•REPORTING
•MEDWATCH
• FDA OVERSIGHT
•SURVEILLANCE
•INSPECTION
•ENFORCEMENT
II. Overview of FDA Regulatory Process: Drugs and Medical Devices
A.Drugs
I. Preclinical Studies
21 USC §355(i)(1)(A)
21 CFR §312.23(a)(8)
A.General
1. No FDA pre-approval required
2. Conducted on laboratory animals
3. Subject to Good Laboratory Practices Regulations (GLP)
21 CFR Part 58
B. Types of Testing
1.Pharmacological
2.Toxicological
II. Investigational Exemption For New Drug (IND)
21 USC §355(i)
21 CFR Part 312
A.Participants
1. Sponsor – manufacturer
2. Clinical investigator – conducts study & obtains informed consent
21 CFR Part 50
3. Institutional review board (IRB) – approves study protocols
B. Content and Format (Form 1571)
21 CFR §312.23
1. Pre-IND meeting with FDA
2. Introductory statement
3. Investigator’s brochure
4. Protocols for each clinical study
5. Chemistry, manufacturing and control information
6. Results of preclinical investigations – pharmacology and toxicology
7. Summary of previous human experience with drug
C. Phases of Human Clinical Studies
21 CFR §312.21
1. Phase 1 – safety
2. Phase 2 – effectiveness
3. Phase 3 – safety and effectiveness
D. Reporting by Sponsor
1. IND safety reports
21 CFR §312.32
2. Annual reports
21 CFR §312.33
3. Information amendments
21 CFR §312.31
4. Protocol amendments
21 CFR §312.30
E. FDA Action
1. Effective date
21 CFR §312.40(b)
2. Clinical hold
21 CFR §312.42
6 ■ Defending Drug and Medical Device Litigation: A Primer for Young Lawyers ■ September 2014
3. Termination
21 CFR §312.44
III. New Drug Application (NDA)
21 USC §355
21 CFR Part 314
A. Required for interstate commerce
B.Criteria
1. Safety
21 USC §355(d)
2. Effectiveness (efficacy) – substantial evidence consisting of
adequate and well-controlled studies
C. Content and Format
21 USC §355(d)
21 CFR §314.126
21 CFR §314.50
1. Application form
2. Comprehensive index
3.Summary
4. Technical sections
5.Statistics
6. Sample of drug
7. Drug labeling
8. Case report forms and tabulations
D. FDA Action
21 USC §355(c)-(f)
21 CFR Part 314 Subpart D
1. Review procedure
Advisory Committee
25 USC Appendix 2
21 CFR Part 14
2. FDA response – approval letter, approvable letter, not approvable letter, refusal
3. Time frames
21 USC §355(c)
4. Fast track products
21 USC §356
IV. Postmarketing Requirements
A. Reporting Requirements
21 USC §355(k)
1. Adverse drug experiences (Form 3500A)
21 CFR §314.80
2. Other postmarketing reports
21 CFR §314.81
B. Adulteration
21 USC §351
21 CFR §314.170
1.Definition
2. Current good manufacturing practice (cGMP) requirements
C. Misbranding
21 CFR Part 211
21 USC §352
21 CFR §314.170
1.Definition
2. Labeling requirements
21 CFR Part 201
3. Prescription drug advertising requirements
21 CFR Part 202
4. Dissemination of treatment information
(off-label)
21 USC §360aaa (omitted)
21 CFR Part 99
D. Registration
21 USC §360
21 CFR Part 207
1.Application
2. Registration of drug establishment (Form 2656)
3. Drug listing (Form 2657)
4. FDA action
E. NDA Supplements
21 CFR §314.70
1. FDA approval
F. Phase 4 Studies
21 USC §356b
21 CFR §312.85
V. FDA Postmarketing Actions
A. Inspection (Form 483)
21 USC §374
1.Authority
2.Scope
3.Procedure
B. Withdrawal of Approval
21 USC §355(e)
21 CFR §314.150
1.Grounds
2.Procedure
C. Enforcement Actions
1. Injunction
21 USC §332
2. Seizure
21 USC §334
3. Recall
21 CFR Part 7 Subpart C
4. Refusal to import of export
21 USC §381
5. Public reports
21 USC §375
6. Civil penalties
21 USC §333
7. Criminal proceedings
21 USC §333
VI. Additional Provisions Relating To Specific Drugs
A. Abbreviated New Drug
Application (ANDA)
21 USC §355(j)
1. Generic Drugs
B. Drugs for Serious or Life Threatening Illnesses
21 CFR Part 314 Subpart H
1. Accelerated approval
C. Orphan Drugs
21 USC §§360aa-dd
21 CFR Part 316
1. Rare diseases
D. Over-the-Counter Drugs (OTC)
21 CFR Part 330
1. Monograph system
E. Biologics
42 USC §262
21 CFR Part 600
1. Animal origin (vaccines, blood)
2. License system
B. Medical Devices
I. Classes of Devices
21 USC §360c
21 CFR Part 860
A. Class I
21 USC §360c(a)(1)(A)
1. Definition
21 CFR §860.3(c)(1)
B. Class II
21 USC §360c(a)(1)(B)
1. Definition
21 CFR §860(c)(2)
C. Class III
21 USC §360c(a)(1)(C)
1. Definition
21 CFR §860.3(c)(3)
D. Classification Procedure
21 USC §360c(b)-(i)
1. Recommended by classification panels or accredited persons
2. Classified by regulation
3. Reclassification
II. Preemption
21 USC §360m
21 CFR §§860.84, .93
21 USC §360k
21 CFR Part 808
A. Prohibits State Law Requirements
1. Different than statutory or regulatory requirements
2. In addition to statutory requirements
III. Premarket Approval (PMA)
21 USC §360e
21 CFR Part 814
A.Scope
1. “New” Class III devices
21 USC §360e(a)
2. “Old” Class III devices
21 USC §360e(b)
B. Investigational Device Exemption (IDE)
21 USC §360j(g)
21 CFR Part 812
1. Required for investigation of Class III device
21 USC §360e(c)
2. Participants – sponsor, investigators, IRB
21 CFR Part 812
Subparts C-E
3. Types – full and abbreviated
21 CFR §§812.20, .2(b), .35
4. Contents and format (full IDE)
21 CFR §812.20
5. FDA Action
21 CFR §812.30
C. PMA Application
21 USC §360e(c)
1. Content and format
D. FDA Action
21 CFR §814.20
21 USC §360e(d)
1. Review procedure – device review team, Advisory Committee
2. Criteria – reasonable assurance of safety and
effectiveness (valid scientific evidence
21 CFR §814.44
21 USC §360c(d)
21 CFR §860.7
3. FDA Action – approval letter, approvable
letter, not approvable letter, denial
21 CFR §§814.44, .45
21 CFR §§814.44, .42
4. Time frames
21 USC §360e(d)
5. Fast track products
IV. 510(k) Notification
21 USC §356
21 USC §360c(f)(1)(A)(ii)
21 CFR Part 807 Subpart E
A. Application
21 CFR §807.81
1. Device substantially equivalent to predicate (legally marketed) device
2. Definition of substantial equivalence
B. Content and Format of Notice
21 USC §360c(i)
21 CFR §807.100
21 CFR §807.92
1. Name of device
2. Registration number of applicant
3. Class of device
4. Performance standard registration
5. Proposed labeling and advertisements
6. Statement of substantial equivalence accompanied by date to support statement
7. Additional information for Class III devices
C. FDA Action
1. Market clearance
21 CFR §807.100
21 CFR §807.97
2.Denial
3.Other
V. Postmarketing Requirements
A. General controls
1. Records and reports (medical device reports - Form 3500A)
21 USC §360i
21 CFR Part 803
2. Adulteration (QSR)
21 USC §351
21 CFR Part 820
3. Misbranding (labeling)
21 USC §352
21 CFR Part 801
4. Registration
21 USC §360
21 CFR Part 807
5. General provisions
21 USC §360j
6. Dissemination of treatment information (off-label)
21 USC §§360aaa
(omitted),396
21 CFR Part 99
B. Special Controls
1. Performance Standards
2. Postmarket surveillance (medical device tracking)
3. Other special controls
21 USC §360d
21 CFR Part 861
21 USC §§360i, 360l
21 CFR Part 821
21 USC §360c
VI. FDA Postmarketing Actions
A. Inspection (Form 483)
21 USC §374
1.Authority
2.Scope
3.Procedure
B. Withdrawal of PMA Approval
21 USC §360e(e)
21 CFR §814.46
1.Grounds
2.Procedure
C.Enforcement
1. Injunction
21 USC §332
2. Seizure
21 USC §334
3. Banned devices
21 USC §360f
21 CFR Part 895
4. Notification/recall
21 USC §360h
21 CFR Part 810
5. Refusal to import or export
21 USC §381
6. Public reports
21 USC §375
7. Civil penalties
21 USC §333
8. Criminal proceedings
21 USC §333
III.Bibliography
1. Food, Drug, and Cosmetic Act 1938, Pub. L. No. 75-717, 52 Stat. 1040 (1938), codified, as
amended, at 21 U.S.C. §301 et seq.
2. Medical Device Amendments of 1976, Pub. L. No. 94-295, 90 Stat. 540 (1976), codified, as
amended, at 21 U.S.C. §§301, 331, 334, 351-52, 358, 360, 374, 381
3. Safe Medical Devices Act of 1990, Pub. L. No. 101-629, 104 Stat. 4511 (1990), codified, as
amended, at 21 U.S.C. §§301 note, 321, 331, 334, 346a, 352-53, 356-57, 360c-d, 371-72, 372a,
376, 381
4. Food and Drug Administration Regulatory Modernization Act of 1997, Pub. L. 105-15, 111,
Stat. 2206 (1997), codified, as amended, at 21 U.S.C. §§321, 343-3, 348, 351, 352, 353, 353z,
355, 355a, 356, 356a, 356b, 356c, 360, 360i, 360j, 360m, 360aa, 360bb, 360cc, 360aaa, 360aaa-1,
360aaa-2, 360aaa-3, 360aaa-4. 360aaa-5, 360aaa-6, 360bbb, 360bbb-1, 360bbb-2, 371, note 374,
379a, 379g, 379h, 379k, 379l, 379o, 379r, 379s, 379b, 381, 382, 383, 393, 396, 397, 26 USC §45C,
35 USC §156, 38 USC §8126, 42 USC §247b-8, 282, 299a-3
5. Food and Drug Administration Amendments Act of 2007, Pub.L. 101-85, 121 Stat. 823 (2007)
6. 21 C.F.R. §§1-1405
7. From Test Tube to Patient: Improving Health Through Human Drugs (Janet Warnock, M.D.,
ed. FDA 1999)
8. FDA Alamanac (FDA Nov. 1997)
9. New Drug Development in the United States (FDA Consumer Special Report Jan. 1995)
10. Pharmaceutical Industry Profile 2005 (PhRMA 2005)
11. K. Simpson, “Overview of FDA Regulatory Process for Drugs and Medical Devices,” Drug and
Medical Device Litigation Seminar handbook (DRI May 4-5, 1995)
12. L. Schnoll, Regulatory Compliance Almanac (Food & Drug Law Institute 2001)
13. I. Berry, The Pharmaceutical Regulatory Process (Food & Drug Law Institute 2004)
14. D. Shelton, Compilation of FDCA-Related Food and Drug Laws (Food & Drug Law Institute
2010)
15. N. O’Flaherty, S. Terman, N. Mathewson, E. Phelps & M. Tolboe, Medical Device Regulation &
Compliance (Food & Drug Law Institute 2010)
16. J. Liu & D. Shelton, FDCA Statutory Supplement (2d ed. Food & Drug Law Institute 2011)
17. D. Adams, R. Cooper, M. Hahn & J. Kahan, Food and Drug Law and Regulation (2d ed. Food
& Drug Law Institute 2014)
18. K. Pina & W. Pines, A Practical Guide to Food & Drug Law and Regulation (5th ed. Food &
Drug Law Institute 2014)
19. M. Levy, Off-Label Communications: A Guide to Sales & Marketing Compliance (4th ed.
Food & Drug Law Institute 2014)
IV.Websites
FDA
www.fda.gov
Advanced Medical Technology Association (HIMA)
www.advamed.org
Pharmaceutical Research and Manufacturers of America (PhRMA)
www.phrma.org
Food & Drug Law Institute
www.fdli.org
Drug and Device Law blog
http://druganddevicelaw.blogspot.com
Products Liability:
Edward W. Gerecke
David J. Walz
Carlton Fields Jorden Burt, P.A.
Corporate Center Three at International Plaza
4221 W. Boy Scout Boulevard, Suite 1000
Tampa, FL 33607-5736
(813) 223-7000
(813) 229-4174
(813) 229-4133 (fax)
[email protected]
[email protected]
Edward W. Gerecke is a shareholder in the Tampa office of Carlton Fields Jorden
Burt, P.A. Ed has devoted most of his 30-year career in the defense of product
liability matters with a specialty in defense of actions involving prescription
drugs, medical devices, and over-the-counter medical products. He has been at
the forefront of development of Florida law in key areas involved in the defense of
such claims, including the learned intermediary doctrine, preemption, statute of
limitations, and expert challenges. Ed is a member of the steering committee of
the DRI Drug and Medical Device Committee. He is certified in Civil Trial by the
National Board of Trial Advocacy and in Civil Pretrial Practice by the National Board
of Pretrial Practice Advocacy. Ed is recognized by the various “best of ” and “super”
lawyer publications for product liability defense. Ed is a member of other defense
organizations such as PLAC and IADC, as well as the American Board of Trial
Advocacy and is past President of the Tampa Bay chapter.
David J. Walz is a shareholder in the Tampa office of Carlton Fields Jorden Burt.
He focuses on the defense of actions involving prescription and over-the-counter
medical products. He has served in the successful representation of drug-and-device
manufacturers in a variety of cases, including the Eleventh Circuit’s first application
of Riegel preemption to bar claims against a PMA device. Dave is a member of the
DRI Drug and Medical Device Committee, Product Liability Committee, and Trial
Tactics Committee, along with various other professional and defense organizations.
He has written and published extensively on removal to federal court, fraudulent
joinder, preemption in medical-device and vaccine cases, mass-tort fraud, and using
the Third Restatement against design-defect claims. For further information about
Dave or Carlton Fields Jorden Burt’s Pharmaceutical and Medical Device Practice,
please visit www.carltonfields.com.
Products Liability:
Table of Contents
I. Products Liability..........................................................................................................................................17
A. Who is Liable?........................................................................................................................................17
B. Types of Product Defects......................................................................................................................17
1.Design.............................................................................................................................................17
2.Manufacturing...............................................................................................................................18
3.Warning..........................................................................................................................................19
C.Causation...............................................................................................................................................20
D. Theories of Liability...............................................................................................................................20
1. Direct Liability...............................................................................................................................21
2. Indirect Liability............................................................................................................................25
E.Defenses.................................................................................................................................................27
1. Learned Intermediary Doctrine....................................................................................................28
2. Comment k.....................................................................................................................................29
3. Federal Preemption.......................................................................................................................30
4. State of the Art...............................................................................................................................35
5. Bulk Supplier Defense....................................................................................................................35
F. Glossary of Key Terminology...............................................................................................................35
II. The Restatement (Third)..............................................................................................................................39
A.Introduction...........................................................................................................................................39
B. Section 2(b): Not Adopted in Green v. Smith & Nephew AHP, Inc., 629 N.W.2d 727 (Wis. 2001).......40
C. Section 6(b): Relied Upon in Stahl v. Novartis Pharmaceuticals Corp., 283 F.3d 254
(5th Cir. 2002)........................................................................................................................................40
D. Section 6(c): Not Adopted in Bryant v. Hoffman-La Roche, Inc., 582 S.E.2d 723
(Ga. App. 2003)......................................................................................................................................41
E. Section 6(c): Not Adopted in Freeman v. Hoffman-LaRoche, Inc., 618 N.W.2d 827 (Neb. 2000)........41
F. Section 6(c): Factual Record Precluded Decision in Hansen v. Baxter Healthcare Corp.,
764 N.E. 2d 35 (Ill. 2002)......................................................................................................................42
G. Section 6(c): Not Adopted in Mele v. Howmedica, Inc., 808 N.E.2d 1026 (Ill. App. Ct. 2004).........42
H. Section 6(c): Adopted in Madsen v. American Home Products Corp., 477 F. Supp. 2d 1025
(E.D. Mo. 2007)......................................................................................................................................42
I. Section 6(c): Adopted in Harrison v. Howmedica Osteonics Corp., No. CIV 06-0745 PHX
RCB, 2008 WL 906585 (D. Ariz. Mar. 31, 2008)..................................................................................43
J. Section 6(c): Applied in Mills v. Bristol-Myers Squibb Co., No. CV 11-00968-PHX-FJM,
2011 WL 4708850 (D. Ariz. Oct. 7, 2011)............................................................................................43
K. Section 6(d): Adopted in Larkin v. Pfizer, Inc., 153 S.W.3d 758 (Ky. 2005).......................................43
III. Off-Label Use, the Dilemma.........................................................................................................................44
A. Statistics Regarding the Use of Off-Label Prescription Drugs and Devices......................................44
B. Off-Label Use Defined...........................................................................................................................45
Products Liability: Claims, Defenses, and Case Handling ■ Gerecke and Walz ■ 15
C. Physician, Not Manufacturer, Liability For Prescribing a Drug and/or Device For an
Off-Label Use.........................................................................................................................................47
D. Manufacturer Lability for Off-Label Use.............................................................................................47
E.Conclusion.............................................................................................................................................50
Products Liability:
I. Products Liability
A. Who is Liable?
1. Strict Liability: Any party in a product’s “chain of commerce” may potentially be held liable if the
product is defective. This includes designers, manufacturers, “apparent manufacturers” (parties
who sell under their own name products manufactured by another), component part manufacturers, distributors, and retailers. Exceptions exist in certain jurisdictions for non-manufacturer defendants based on statutes or case law holding that the non-manufacturer distributor,
for example, was merely a conduit for the product. See, e.g., Ga. Code Ann. §51-11.1; Wheat v.
Sofamor, S.N.C., 46 F. Supp. 2d 1351, 1365-66 (N.D. Ga. 1999).
2. Negligence: Rather than the distributive chain, the concept of duty governs the proper parties to
a products liability action based on negligence. Generally, if the party owed a duty of care to the
plaintiff and the plaintiff can establish a breach of that injury and resulting injury caused by that
breach, then the party may liable under negligence. See Cintron v. Osmose Wood Preserving, Inc.,
681 So. 2d 859 (Fla. Dist. Ct. App. 1996).
B. Types of Product Defects
Although several legal bases exist for products liability claims, all of them require proof that the
product was defective. Three types of product defects are recognized: design, manufacturing, and warning.
Brown v. Superior Court, 751 P.2d 470 (Cal. 1988); Barker v. Lull Eng’g, 573 P.2d 443 (Cal. 1978).
1. Design
A design defect occurs when a product is nonetheless dangerous to users even though it was manufactured in accordance with specifications. If a product has a defective design, that defect will appear in every
unit of the product, making design defects particularly dangerous because of the potential for mass litigation.
Benitez v. Synthes, Inc., 199 F. Supp. 2d 1339, 1344 (M.D. Fla. 2002).
Generally, a product may be considered defective in design either (1) if the product fails to meet the
expectations of the ordinary consumer (the “consumer expectation” test), or (2) if the risks inherent in the
challenged design outweigh the benefits, or the design embodies “excessive preventable danger” (the “riskbenefit” test). See Barker v. Lull Eng’g, 573 P.2d 443 (Cal. 1978); see also Martin v. Teletronics Pacing Systems,
Inc., 105 F.3d 1090, 1099 (6th Cir. 1997), cert. denied 522 U.S. 1075 (1998) (applying Ohio case law regarding consumer expectation test); Apperson v. E.I. du Pont de Nemours & Co., 41 F.3d 1003, 1106 (7th Cir. 1994)
(applying Illinois case law regarding consumer expectation test); Bravman v. Baxter Healthcare Corp., 984 F.2d
71, 75-76 (2d Cir. 1993) (applying New York law regarding risk-utility test). Most plaintiffs prefer the consumer expectation test because it may not require expert testimony; the jury can simply determine whether
the product meets ordinary expectations.
How Useful is the Consumer Expectation Test? Courts appear to be recognizing that the consumer
expectation test is unworkable when the product is sufficiently complex that an ordinary consumer has no
reasonable expectation of how it should perform. For example, in Soule v. General Motors, the plaintiff was
injured when, in a head-on collision, the wheel assembly of her car crumpled into the driver’s compartment.
See 882 P.2d 298 (Cal. 1994). The California Supreme Court stated that the consumer expectation test should
not apply in cases where the ordinary person has no idea of how the product should perform. The court limited the consumer expectation test to design defect “cases in which the everyday experience of the product’s
users permits a conclusion that the product’s design violated minimum safety assumptions, and is thus defective regardless of expert opinion about the merits of the design.” In other words, the test would apply when
“the product’s design performed below the legitimate, commonly accepted minimum safety assumptions of its
ordinary consumers.” Id. at 308.
Application of Consumer Expectation Test to Prescription Medical Product Cases. Courts have considered whether the limitation described in Soule will apply to prescription medical product cases. Unlike other
products, prescription medical products involve the learned intermediary doctrine, which recognizes that
manufacturers must sufficiently warn prescribing physicians, not end users. See, e.g., Garside v. Osco Drug,
Inc., 976 F.2d 77, 80 (1st Cir. 1992) (applying Massachusetts law). For those jurisdictions applying the consumer expectation test, the physician should be considered the consumer. Many courts reason that the actual
consumers of prescription medical products lack any expectations about the performance and safety of those
products. See In re Zyprexa Prods. Liab. Litig. v. Eli Lilly & Co., 489 F. Supp. 2d 230, 267 (E.D.N.Y. 2007) (applying Pennsylvania law) (prescriber is “intended user”); Craft v. Peebles, 893 P.2d 138, 154-55 (Haw. 1995). Thus,
if a consumer expectation instruction is given in a prescription medical product case, then the court should
instruct the jury to view the “ordinary consumer” as the “ordinary physician” or “ordinary surgeon.” Zimmer,
Inc. v. Birnbaum, 758 So. 2d 714, 715 (Fla. Dist. Ct. App. DCA 2000). Other jurisdictions, however, refuse to
view the prescribing physician as the final consumer and rely on patients’ expectations of the prescription
medical product for the consumer expectation test. See Mele v. Howmedica, Inc., 808 N.E.2d 1026, 1037-38
(Ill. App. Ct. 2004).
Restatement (Third) of Torts and Consumer Expectation Test. Notably, the Restatement (Third) of
Torts: Products Liability, released in 1998, eliminates the consumer expectation test from its general definition of design defect. Instead, a product is defective in design “when the foreseeable risks of harm posed by
the product could have been reduced or avoided by the adoption of a reasonable alternative design.” Restatement (Third) of Torts: Product Liability §2(b). Comment g to section 2(b) states that “consumer expectations
do not constitute an independent standard for judging the defectiveness of product designs,” although such
expectations may be relevant to the risk-benefit balancing. Restatement (Third) of Torts: Product Liability
§2(b) cmt. g (1998).
The Third Restatement also includes, in a separate section, a very narrow definition of design defect
that applies only to prescription drugs and medical devices. It states that a design defect exists “if the foreseeable risks of harm posed by the drug or medical device are sufficiently great in relation to its foreseeable
therapeutic benefits that reasonable health care providers, knowing of such foreseeable risks and therapeutic benefits, would not prescribe the drug or medical device for any class of patients.” Restatement (Third) of
Torts: Products Liability §6(c).
Under this definition, so long as a reasonable physician would prescribe the product for some class of
patients, it is not defective in design.
2. Manufacturing
A manufacturing defect occurs when a product fails to meet the manufacturer’s specifications, usually as a result of some flaw in the manufacturing process. See Brown v. Superior Court, 751 P.2d 470 (Cal.
1988); Barker v. Lull Eng’g, 573 P.2d 443 (Cal. 1978); see generally Parkinson v. Guidant Corp., 315 F. Supp. 2d
741 (W.D. Pa. 2004) (applying Pennsylvania law). Unlike a design defect, a manufacturing defect will typically
appear only in one unit or one lot of the product. Under the Restatement (Third), the definitions of manufacturing defect in the generic definition of “defects” and in the special section devoted to prescription products
are identical. Restatement (Third) Torts: Products Liability §§2(a), 6(b)(1).
Generally, to sustain a manufacturing defect claim for a prescription medical product, a plaintiff
must prove (1) the existence of a manufacturing flaw that results in product characteristics other than those
the manufacturer intended; (2) that this defect existed when the product left the defendant’s control; and (3)
that the defect caused the plaintiff ’s injury. See Saraney v. Tap Pharm. Prods., No. 1:04 CV 02026, 2007 WL
148845, at *7 (N.D. Ohio Jan. 16, 2007) (applying Ohio law).
3. Warning
A warning defect occurs when, even though the product is properly designed and manufactured,
purchasers and users are not provided with warnings of the risks that are necessary to ensure safe and proper
use. Generally, the manufacturer has a duty to warn of those risks that are known or reasonably knowable at
the time of sale. See, e.g., Wolicki-Gables v. Arrow Int’l, Inc., 641 F. Supp. 2d 1270, 1286 (M.D. Fla. 2009) (applying Florida law); Anderson v. Owens-Corning Fiberglas, Inc., 810 P.2d 549 (Cal. 1991). However, the manufacturer need not warn of risks that are obvious to the consumer. The restriction of liability to risks known
or knowable (in some instances, scientifically knowable) at the time of sale reflects policy judgments that (1)
liability for unknown risks will create disincentives to research and development, and (2) that it is difficult
to insure against unknown risks, defeating the risk-spreading goal of product liability. It also recognizes that
strict liability is not absolute liability.
In the area of warnings, medical products are treated very differently from ordinary consumer products. With respect to prescription drugs and medical devices, the general rule is that the warning must be provided to the physician, not to the patient. See Reyes v. Wyeth Labs., 498 F.2d 1264, 1276 (5th Cir. 1974), cert.
denied 419 U.S. 1096 (1974); Carlin v. Superior Court, 920 P.2d 1347 (Cal. 1996); Martin v. Hacker, 628 N.E.2d
130, 1311 (N.Y. 1993). The manufacturer has no further obligation to ensure that the warnings reach the
patient and will not be held liable for the physician’s failure to pass the warnings along to patients. The policy
underlying the rule is that the physician acts as a “learned intermediary” between the manufacturer and the
patient; the “learned intermediary rule” is an important defense for medical products manufacturers, which is
discussed further infra.
There are some limited exceptions to this general rule, where the manufacturer is required to provide
warnings directly to the consumer. The first among these arose in the case of mass vaccinations, where physicians inoculate all patients without making a genuine assessment of the risks and benefits for each patient.
The second example is in the case of oral contraceptives, where the FDA requires that manufacturers supply
detailed package inserts with the product when it is dispensed by the pharmacy.
The Restatement (Third) incorporates these concepts by stating that a warning defect exists when
“reasonable instructions regarding foreseeable risks of harm” are not provided to:
a. prescribing and other health-care providers who are in a position to reduce the risks of harm in
accordance with the instructions or warnings; or
b. the patient, when the manufacturer knows or has reason to know that health-care providers will
not be in a position to reduce the risks of harm in accordance with the instructions or warnings.
Restatement (Third) of Torts: Products Liability §6(d).
Manufacturers are required to submit all proposed packaging and labeling to the FDA for review
before the FDA will clear the drug or device for sale. Manufacturers are not permitted to distribute any labelProducts Liability: Claims, Defenses, and Case Handling ■ Gerecke and Walz ■ 19
ing or packaging that has not been reviewed and cleared by the FDA, and must seek FDA permission to revise
or alter packaging and labeling. However, the fact that the FDA reviewed the labeling prior to sale does not
establish per se that the warnings are adequate, and a manufacturer still may be held liable even if the FDA
cleared the labeling. See Foyle v. Lederle Labs., 674 F. Supp. 530, 535 (E.D.N.C. 1987) (applying North Carolina law); Carlin v. Super. Ct., 920 P.2d 1347 (Cal. 1996). Evidence of compliance with FDA requirements is
admissible evidence of adequacy of warnings, even though it is not dispositive. Certain jurisdictions allow a
presumption or create a rebuttable presumption that compliance with FDA requirements or government regulations in general renders the product’s warnings adequate or non-defective. See, e.g., Perez v. Wyeth Labs. Inc.,
734 A.2d 125, 129 (N.J. 1999); see generally Fla. Stat. Ann. §768.1256; Mich. Comp. L §600.2946(4); N.J. Stat.
Ann. §2A:58C-4; Tex. Rev. Civ. Prac. & Rem. C. §82.007.
On occasion, a manufacturer will request that a certain risk be included in the labeling, and the FDA
will refuse, usually on grounds that there is insufficient evidence that the risk is genuine or sufficiently linked
to the product. In such a case, if a patient is injured when this risk occurs, the manufacturer should not be
held liable despite the absence of a warning. The state cannot impose liability on the manufacturer for failing
to do something that the FDA expressly stated it could not do. See infra Section V.C. Federal Preemption.
C.Causation
In addition to proving the existence of a defect in the product, the plaintiff must link that defect to
the claimed injury or damage. See Lawrence v. Sofamor, No. 95-CV-1507, 1999 WL 592689, at *5 (N.D.N.Y.
Aug. 2, 1999) (applying New York law) (device) (“causation is an indispensable element for each of plaintiffs’
claims). In most instances, the plaintiff will need a competent expert who can testify to causation to a “reasonable degree of medical probability.” Jones v. Ortho Pharm., 163 Cal. App. 3d 396 (1985).
Two types of causation apply to drug and device cases: general and specific. General causation asks
whether there is scientific evidence to show that the product can cause the type of injury alleged. If general causation can be shown, specific causation looks at whether the product, in fact, caused this plaintiff ’s injuries.
The causation element is where issues of admissibility of scientific evidence or opinions can be challenged under the Daubert (applied by federal courts and a majority of states that apply a similar standard),
Frye (a minority of state courts), Daubert-Frye hybrid (other states), or state-specific (remaining states) tests.
The Frye standard was stated in its original form in Frye v. U.S., 293 F. 1013, 1014 (D.C. App. 1923), and mandates that test results used as evidence must be generally accepted within the relevant portions of the scientific
community, and excludes from evidence any test results from scientifically unproven methods. The standard
thus also is referred to as the “general-acceptance” standard.
A separate method for evaluation of scientific findings for admission as evidence is the “sound-methodology” standard applied in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993). In Daubert, the
Court held that the Federal Rules of Evidence, and specifically Rule 702, require trial judges to ensure that scientific testimony admitted is both reliable and relevant. Id. at 589. Scientific opinions must be both generally scientifically reliable (i.e., supported by generally accepted scientific evidence), and appropriately applicable to the
particular plaintiff ’s condition. In the proper setting and under the correct circumstances, Daubert provides a
powerful defense against causation. See, e.g., In re Denture Cream Prods. Liab. Litig., 795 F. Supp. 2d 1345 (S.D.
Fla. 2011); In re Bextra & Celebrex Mktg. Sales Practices & Prod. Liab. Litig., 524 F. Supp. 2d 1166 (N.D. Cal. 2007).
D. Theories of Liability
Regardless of whether the plaintiff alleges a defect in design, manufacture, or warnings, he must
prove that defect under a legal theory of liability. Several causes of action may support a products liability
claim, including strict liability, negligence, breach of warranty, and fraud. The theories break down into two
main categories: direct theories (where the plaintiff has proof of exposure to the specific defendant’s product),
and indirect theories (where the plaintiff can prove exposure to a class of products but not to that of any particular manufacturer).
1. Direct Liability
Theories of direct liability apply when the plaintiff has evidence of exposure to a particular defendant’s product. For example, there may be only one manufacturer of a particular product, or the manufacturer’s name may appear on the product. In addition, purchasing, prescription, or pharmacy records may
indicate whose product was in use.
a.Strict liability
Because of the relative ease of proof, strict liability is the most common theory pleaded by plaintiffs.
Developed in California in the 1960s, strict liability was based on the principle that, in an era of mass production, the manufacturer is in a better position than the consumer both to identify and remedy product defects
and to spread the risk of injuries from defective products. Greenman v. Yuba Power Prods., Inc., 377 P.2d 897
(Cal. 1963).
In general, strict liability requires that the plaintiff prove each of the following: (1) a defect in the
product; (2) exposure to or use of the defendant’s product; (3) injury caused by the defect; and (4) damages.
Strict liability removes from the analysis the degree of care taken by the manufacturer. A manufacturer may have used all possible care in the design and manufacturer of the device and accompanying warnings, but still be held liable for the plaintiff ’s injuries. At the same time, strict liability is not absolute liability,
and the manufacturer is not an insurer of its products. Some jurisdictions require that plaintiff prove the
necessary defect, whether in manufacture, design, or warning, by expert testimony. See, e.g., Savage v. Danek
Med., Inc., 31 F. Supp. 2d 980, 983 (M.D. Fla. 1999); Haggerty v. Upjohn Co., 950 F. Supp. 1160, 1168 (S.D. Fla.
1996). In addition, in the case of warning defects, the “known or knowable” standard infuses negligence concepts into strict liability.
With respect to proving exposure to the product, this can be very difficult in the case of some products. A significant amount of time may lapse between exposure to the product and the onset of injury, or
the plaintiff may not know whose product was used. For the most part, proof of exposure to the defendant’s
product remains the plaintiff ’s burden, and only in very limited circumstances (discussed below) will the
plaintiff be excused from this requirement.
As for causation, the plaintiff must present testimony of a competent expert that, to a reasonable
degree of medical probability, the injuries were proximately caused by the product. See Jones v. Ortho Pharm.
Corp., 209 Cal. Rptr. 456 (1985). The “mere possibility” or “evenly balanced” probabilities fail to meet the
plaintiff ’s burden of proof. Gooding v. Univ. Hosp. Bldg., Inc., 445 So. 2d 1015, 1020 (Fla. 1984); see Guinn v.
AstraZeneca Pharm. LP, 602 F.3d 1245 (11th Cir. 2010) (expert’s speculation insufficient).
The concept of proximate cause includes proof both that the product is capable of causing the
claimed injury (general causation) and that it, in fact, caused the injury in the plaintiff ’s case (specific causation). On the latter element, the expert must prove that the product was a “substantial factor” in bringing
about the injury. Rutherford v. Owens-Ill., Inc., 941 P.2d 1203 (Cal. 1997).
Although courts have been reluctant to define the term “substantial factor,” it is clear that the connection must be more than “theoretical” or “infinitesimal.” Id. Moreover, “the mere fact that a person suffered injury while using a product is insufficient in itself to satisfy the requirement of proof that a defect in the
product was a proximate cause of the injury.” Samarah v. Danek Med., Inc., 70 F. Supp. 2d 1196, 1206 (D. Kan.
1999) (applying Kansas law) (device). A plaintiff also cannot ask a jury to infer causation from the totality of
the circumstances. See, e.g., Cottle v. Superior Court, 5 Cal. Rptr. 2d 882 (1992).
“Competent expert testimony” requires both that the expert is qualified to express the opinion and
that the information upon which the expert relies is of a type upon which experts in the field reasonably rely.
This latter requirement, set forth in Federal Rule of Evidence 702, will bring into play issues of “junk science”
addressed in Daubert and related state court concepts.
b.Negligence
Negligent products liability is the same as negligence in any other context. It requires:
a. proof of a duty of care on the part of the defendants;
b. breach of that duty;
c. injuries caused by the breach; and
d.damages.
What sets negligence apart from strict liability is its additional requirement of proof that the defendant did not act as a reasonably prudent manufacturer, distributor, pharmacy, and so forth would have acted
under the circumstances. Evidence regarding efforts made to maximize the safety of the product is therefore
highly relevant, as is evidence of actions of the rest of the industry—although conformance to industry standards is not dispositive of due care, because a jury could find that the entire industry is negligent. Similarly, as
described above, compliance with FDA or other regulatory requirements is also not dispositive of due care,
though it is admissible. On the other hand, as discussed above regarding warnings, the FDA’s or another agency’s refusal to let a manufacturer take certain action or provide a certain warning can be a complete defense to
a negligence claim.
Standards of causation in a negligence action are the same as causation for strict liability.
c.Breach of express warranty
Many complaints in drug and device cases also contain allegations of a breach of express warranty,
claiming that the manufacturer provided an “express affirmation of fact or promise.” Basko v. Sterling Drug,
Inc., 416 F.2d 417, 428 (2d Cir. 1969) (applying Connecticut law); see also Perfetti v. McGahn Med., 662 P.2d
646, 653 (N.M. Ct. App. 1983), cert. denied 662 P.2d 645 (N.M. 1983). General statements regarding the safety
or effectiveness of a medical product are not sufficient to establish an express warranty. See Giles v. Wyeth, 500
F. Supp. 2d 1063, 1070-71 (S.D. Ill. 2007) (applying Illinois law).
An express warranty is one that can be given only by the manufacturer. The plaintiff must prove that
the manufacturer in fact did provide a warranty, and must prove the terms of the warranty, the manner in
which it was breached, and that notice of the breach was given to the seller. Evraets v. Intermedics Intraocular,
Inc., 34 Cal. Rptr. 2d 852 (1994). Moreover, a manufacturer can include language in its packaging that disclaims any express warranty. The disclaimer, however, must display a certain level of specificity. See Rite Aid
Corp. v. Levy-Gray, 894 A.2d 563, 573 (Md. 2006) (“the general statement did not negate the effect of the more
specific assertion as to the administration of the [drug] when the entire document is read as a whole”); Fogo v.
Cutter Labs., Inc., 137 Cal. Rptr. 417, 425 (Ct. App. 1977).
Further, some courts require direct privity in breach of express warranty claims. Compare Barrow
v. Bristol-Myers Squibb, No. 96-689-CIV-ORL-19B, 1998 WL 812318, at *46 (M.D. Fla. Oct. 29, 1998), aff ’d
without opinion 190 F.3d 541 (11th Cir. 1999) (applying Florida law) with Morgan v. Abco Dealers, Inc., 01 Civ.
9564 (PKL), 2007 WL 4358392, at *7 (S.D.N.Y. Dec. 11, 2007) (applying New York law).
From a practical perspective, these claims usually stand or fall with the strict liability and negligence
claims. If there is no defect in the product, then the plaintiff will have failed to prove a breach of any warranty.
Even if there is a product defect, it is rare that a plaintiff will have given notice of the breach to the defendant
prior to filing the lawsuit.
d.Breach of implied warranties
In addition to express warranties, additional warranties exist that are implied in every contract of
sale. The two such warranties generally recognized under the Uniform Commercial Code (U.C.C.) are the
implied warranties of merchantability and fitness for a particular purpose. U.C.C. §§2-314; 2-315. Several
states merge these two forms of warranties with other warnings-based theories and no longer give these
claims independent significance. See, e.g., Miller v. Pfizer, Inc., 196 F. Supp. 2d 1095, 1118 (D. Kan. 2002), aff ’d
356 F.3d 1326 (10th Cir. 2004), cert. denied 543 U.S. 917 (2004) (applying Kansas law). For those states that
recognize breach of implied warranties as a separate cause of action, most apply the same standards to those
claims as used in warnings claims. See Rutherford v. Merck & Co., 428 F. Supp. 2d 842, 850 n.1 (S.D. Ill. 2006)
(applying Illinois law).
In the context of medical products, because it is the physician, and not the patient, who stands in the
shoes of the “consumer,” some courts hold that it is the physician to whom such warranties are directed. Carlin
v. Superior Court, 920 P.2d 1347 (Cal. 1996).
As with express warranties, different jurisdictions reach different conclusions regarding whether
direct privity is required in breach of implied warranty claims. Compare Montgomery v. Davol, No. 3:07cv176/
RV/EMT, 2007 WL 2155644, at *2-*3 (N.D. Fla. July 24, 2007) (applying Florida law) with Ackermann v. Wyeth
Pharm., 471 F. Supp. 2d 739, 744 (E.D. Tex. 2006) (applying Texas law).
Some jurisdictions permit manufacturers to expressly disclaim implied warranties. See Music Acceptance Corp. v. Lofing, 39 Cal. Rptr. 2d 159 (1995). To do so, the disclaimer must appear “conspicuously” in the
product labeling.
i. Of merchantability
The implied warranty of merchantability is a guarantee only that the product is suitable for its
intended purpose and is intended to create a minimum level of quality. This implied warranty; unless disclaimed, is applicable to all products. However, as a practical matter, although often included in a complaint, it
is not typically a significant part of the plaintiff ’s case. Proof of a breach of the implied warranty will, at a minimum, require proof that the product is defective; if the plaintiff can prove a defect, he is far more likely to rely
on strict liability than on an implied warranty theory. In addition, unless the product contains a manufacturing defect, it is unlikely that it will fail to meet minimum expectations of quality.
ii. Of fitness for a particular purpose
The implied warranty of fitness for a particular purpose arises when the seller is aware that the purchaser is looking for a product suitable for a particular described need and is relying on the seller’s judgment
in selecting the best product for that need. As a practical matter, this claim often fails as a matter of law in
the prescription medical products field because plaintiffs typically use such products for only their ordinary
purpose, i.e. the labeled indication, and rely on their prescriber rather than the product manufacturer. See
Ackermann v. Wyeth Pharm., 471 F. Supp. 2d 739, 745 (E.D. Tex. 2006); Johnson v. Medtronic, Inc., C.A. No.
H-03-4186, 2005 WL 1515402, at *5 (S.D. Tex. June 23, 2005); Doe v. Solvay Pharm., Inc. 350 F. Supp. 2d 257,
265 (D. Me. 2004).
e.Fraud
Fraud in the products liability realm has the same requirements as fraud in any other context: (1)
representations made by defendant; (2) knowledge that the representations are false and made with intent to
induce plaintiff ’s reliance; (3) reliance by plaintiff; and (4) resulting damages.
Fraud is often alleged in complaints because, as an intentional tort, it provides a vehicle for punitive
damages that are otherwise possibly difficult to recover. However, for products where there is an intermediary,
it is usually difficult for the plaintiff to meet the element of reliance upon the defendant’s representations, as
the plaintiff seldom relies on the manufacturer’s representations.
A plaintiff may also allege fraud in addition to other causes of action as a means of avoiding a statute of limitations defense. The fraud allegation is often incidental to the other tort claims alleged. At least one
jurisdiction has strong case law against this practice. New York courts repeatedly hold that “[c]ourts will not
apply the fraud statute of limitations if the fraud allegation is only incidental to the claim asserted; otherwise
fraud would be used as a means to litigate stale claims.” Hanlon v. Gliatech, Inc., No. CV–07–1737 (SJF)(AKT),
2008 WL 4773430, at *3 (E.D.N.Y. Oct. 27, 2008) (claims against the manufacturer barred by the statute of
limitations).
f. Negligent misrepresentation
Negligent misrepresentation is essentially the same as fraud, except that the element of intent is
replaced by negligence or recklessness regarding the truth of the representation. It is, for all practical purposes,
not very different from a negligent failure to warn claim, and therefore not seriously pursued very often.
g.Consumer Protection Statutes
State consumer protection statutes vary, but often require a lesser burden of proof than necessary
under common law claims, allow multiple or punitive damages, and provide for recovery of attorneys’ fees.
See, e.g., Scott v. GlaxoSmithKline Consumer Healthcare LP, No. 05 C 3004, 2006 WL 952032, at *2 (N.D. Ill.
April 12, 2006) (applying Illinois law); Cona v. Merck & Co., Nos. ATL-L-3553-05 ATL-L1296-05, 2007 WL
2011773 (N.J. Super. Law Div. June 15, 2007). Most such statutes limit recovery to economic loss while a limited few extend to personal injury damages. Compare Doe v. Solvay Pharm., Inc., 350 F. Supp. 2d 257, 274 n. 13
(D. Me. 2004) (applying Maine law) with Maillet v. ATF-Davidson Co., 552 N.E.2d 909, 925 (Mass. 1990).
Common defenses include territoriality, safe harbor provisions based on regulatory compliance
(including compliance with FDA regulation of product labeling and marketing), lack of standing, failure to
properly allege an injury, preemption, causation, and the learned intermediary doctrine. Like the statutes
themselves, the available defenses vary by jurisdiction.
h.Medical Monitoring
Medical monitoring claims deal with recovery for the cost of future medical procedures and surveillance for plaintiffs with no current injury but an allegedly greater risk of developing latent diseases from the
use of, or exposure to, a product. See In re Paoli R.R. Yard PCB Litig., 916 F.2d 829, 850 (3d Cir. 1990) (applying Pennsylvania law) (“an action for medical monitoring seeks to recover only the quantifiable costs of periodic medical examinations necessary to detect the onset of physical harm”).
There is a distinct split in state law, where one line of authority rejects the idea of recognizing medical monitoring damages for fear of overcompensating plaintiffs in the face of an absence of physical injury.
See Ball v. Joy Techs., Inc., 958 F.2d 36 (4th Cir. 1991), cert. denied 502 U.S. 1033 (1992) (applying Virginia
law) (rejecting independent claim for medical monitoring); see also Wood v. Wyeth-Ayerst Labs., 82 S.W.3d
849 (Ky. 2002) (requiring actual physical injury).
The second line of authority recognizes medical monitoring for policy reasons. See, e.g., Ayers v.
Township of Jackson, 525 A.2d 287, 311-12 (N.J. 1987) (court held that “public interest in early detection and
treatment of disease” is an appropriate policy justification for the adoption of medical monitoring damages);
see also Sutton v. St. Jude Medical S.C., Inc., 419 F.3d 568 (6th Cir. 2006) (alleged increased risk is sufficient for
current medical monitoring and standing); Petito v. A.H. Robins Co., Inc., 750 So. 2d 103, 105-107 (Fla. Dist.
Ct. App. 1999), review denied 780 So. 2d 912 (Fla. 2001).
To establish a claim for medical monitoring based on a plaintiff ’s exposure to a drug or medical
device, various states require different elements. For example, a general list of elements required by assorted
states may include (1) exposure at greater than normal background levels, (2) to a proven hazardous substance, (3) caused by the defendant’s negligence, (4) as a proximate result of the exposure, plaintiff has a significantly increased risk of contracting a serious latent disease, (5) a monitoring procedure exists that makes
the early detection of the disease possible, (6) the prescribed monitoring regime is different from that normally recommended in the absence of the exposure, and (7) the prescribed monitoring regime is reasonably
necessary under contemporary scientific principles.
2. Indirect Liability
In some instances, the plaintiff will be unable to prove whose product he used or to which product he
was exposed. For example, the physician may prescribe a generic drug, and the pharmacy may have given the
plaintiff the product of any one of several manufacturers. Or, a physician may use several devices that provide
the same treatment, and it is unknown which device was used on the plaintiff. Thus, a plaintiff may have been
exposed to several products and be unable to identify which one caused the injury.
In such cases, the plaintiff may try to shift the burden of proof to the defendants, to prove that plaintiff was not exposed to its product. This burden-shifting may occur in several ways, although there seems to be
a trend away from expansive burden-shifting, and the courts have been extremely cautious in applying these
theories to shift the burden of proof.
a.Alternative liability: Summers v. Tice
Alternative liability may be employed when there are two defendants, only one of whom caused the
injury, but there is no means for plaintiff to show which one is at fault. The theory was developed in Summers v. Tice, in which the plaintiff was shot in the eye by one of two hunters. 33 Cal. 2d 80 (1984). Both hunters had negligently fired in plaintiff ’s direction, but obviously only one of them could have hit him, and it
was impossible for the plaintiff to prove which. The court shifted the burden to the defendants to exculpate
themselves, and if they could not, both would be held jointly and severally liable. The court held that, because
both defendants had been equally negligent, and one of them was undeniably at fault, fairness dictated that
they bear the costs of the injury instead of the innocent plaintiff. The Summers rule was later adopted in the
Restatement (Second) of Torts section 433B.
Several subsequent cases have refused to expand Summers liability beyond the described circumstances. See, e.g., Setliff v. E. I. DuPont de Nemours, 38 Cal. Rptr. 2d 763 (1995) (declining to expand doctrine
to chemicals); Lineweaver v. Plant Insulation Co., 37 Cal. Rptr. 2d 902 (1995) (asbestos); see also Sanderson v.
IFF, 950 F. Supp. 981 (C.D. Cal. 1996) (fragrances). All of these cases have emphasized the requirements that
(1) all defendants be before the court; (2) that all defendants have acted equally tortiously; and (3) that one
defendant undoubtedly caused the injury. Many cases have rejected alternative liability where fewer than all of
the manufacturers of the product were named defendants, or where each manufacturer’s product was slightly
different and thus not equally dangerous.
b.Concert of action
A second theory that plaintiffs attempt to plead when they cannot prove exposure to a particular
defendant’s product is “concert of action.” This theory is set forth in the Restatement (Second) of Torts section
876, which permits the theory to be proven in any of the following ways:
• the parties have a “common design” to commit a tortious action;
• one party knows the other’s conduct is a breach of duty but nonetheless gives assistance or
encouragement; or
• one party gives substantial assistance to another in committing a tort and his actions, considered
independently, are themselves tortious.
Concert of action is much like conspiracy. The defendants create a common plan to commit a tort
and either take part in it or lend assistance or encouragement.
Courts have also been reluctant to apply this theory in the products field. For example, in Sindell v.
Abbott Laboratories, 607 P.2d 924 (Cal. 1980), the plaintiffs asserted that concert of action liability was appropriate because the manufacturing defendants failed to adequately test DES or provide sufficient warnings
about the drug’s risks, and because they relied on each others’ tests and marketing techniques. The court held
that these activities are common among competitors in the same industry and that the application of concert
of action liability under the circumstances would make a manufacturer liable for the acts of the entire industry, even if that defendant had no connection to the plaintiff ’s injury.
c.Enterprise or industry-wide liability
“Enterprise” or “industry-wide” liability was first discussed in a federal case, Hall v. E.I. duPont de
Nemours, where the plaintiffs sued all the manufacturers of blasting caps, and their trade association. See 345
F. Supp. 353 (E.D.N.Y. 1972). There was evidence that all manufacturers adhered to industry-wide standards
on safety features, design, and manufacture and that the manufacturers had delegated to the trade association certain responsibilities for safety investigation. The court in Hall held that, provided plaintiffs could prove
their caps were manufactured by one of the defendants, the burden on causation would shift to the defense,
on the theory that the various manufacturers had acted as a single industry or enterprise, and that all should
therefore bear liability for injuries resulting from any manufacturer’s product.
Enterprise liability was discussed at length (and rejected) in Sindell v. Abbott Laboratories on several
grounds. See 607 P.2d 924 (Cal. 1980). First, as the Hall court itself said, the principle is applicable only to centralized industries that have a small number of manufacturers; DES was not such an industry. Second, the Sindell plaintiffs made no allegation that the manufacturers had delegated responsibility to a trade association, and
thus there was no indication that they “jointly controlled” the risks associated with DES. Finally, the Sindell court
noted that the industry-wide standards upon which the plaintiffs relied were controlled by the FDA. Although
FDA compliance does not excuse liability, the court found it unfair to impose liability on a manufacturer who did
not supply the specific injury-producing product simply because that manufacturer followed FDA regulations.
d.Market share liability: Sindell v. Abbott Laboratories
In 1980, the concept of indirect liability expanded dramatically through the California supreme
court’s decision in Sindell v. Abbott Laboratories, 607 P.2d 924 (Cal. 1980). There, the court held that, where
several manufacturers market a fungible product, they will be held liable for the plaintiff ’s damages in proportion to their shares of the market for that product at the time of sale.
Sindell involved a group of women plaintiffs whose mothers had taken DES during pregnancy to
avoid miscarriage; plaintiffs alleged that their mothers’ ingestion of DES caused reproductive cancers in “DES
daughters.” Because of the passage of time, it was nearly impossible for plaintiffs to show whose DES each
plaintiff ’s mother had taken. Moreover, each of the nearly 200 DES manufacturers used an identical formula.
Drawing on what it perceived to be the best elements of the various indirect liability theories, Sindell
created a new form of liability, which it called “market share”:
If a plaintiff, through no fault of his own, cannot identify the specific manufacturer of a fungible product which caused injury, and if the plaintiff joins defendants representing a substantial
share of the market for that product, then each defendant will be held liable for plaintiff ’s damages in proportion to its share of the market unless it can exculpate itself.
The decision was ultimately based on public policy: that negligent defendants should be liable rather
than innocent plaintiffs, and that defendants are in the best position both to guard against product risks and
to spread the loss through insurance.
Several states have adopted market share liability in the DES context. See McCormack v. Abbott Labs.,
617 F. Supp. 1521, 1526 (D. Mass. 1985) (applying Massachusetts law); Conley v. Boyle Drug Co., 570 So. 2d
275, 284 (Fla. 1990). However, the majority of states do not adopt market share liability outside the DES litigation. Compare Ray v. Cutter Labs., 754 F. Supp. 193, 195 (M.D. Fla. 1991) (applying Florida law) (applied market share liability to blood products) with In re Factor VIII or IX Concentrate Blood Prods. Litig., No. 94-0382,
2000 WL 282787, at *10 (E.D. La. Mar. 14, 2000) (applying Louisiana law) (refusing to apply market share liability to blood products). Market-share theory remains, as the Restatement reflects, a very narrow exception
to the basic rule placing on plaintiffs the burden of proving causation.
There are several variants of market share liability. However, the basic elements suggested to decide
whether to adopt a market share theory are generalized in the Restatement (Third) of Torts:
(1) the generic nature of the product; (2) the long latency period of the harm; (3) the inability of
plaintiffs to discover which defendant’s product caused plaintiff ’s harm, even after exhaustive
discovery; (4) the clarity of the causal connection between the defective product and the harm
suffered by plaintiffs; (5) the absence of other medical or environmental factors that could have
caused or materially contributed to the harm; and (6) the availability of sufficient ‘market share’
data to support reasonable apportionment of liability.
Restatement (Third) of Torts: Products Liability §15 cmt. c.
If the plaintiff meets all of the requirements, the burden shifts to the defendants to exculpate themselves by proving that the plaintiff could not possibly have been exposed to their products. If defendants cannot exculpate themselves, each will be held liable for the plaintiff ’s damages in proportion to their shares of
the market for the product at the time of sale.
E.Defenses
Because of the unique nature of medical products, their complexity, and the manner in which they
are provided to consumers, as well as the importance to society of low costs for medical products and continued innovation, a number of defenses have developed that specifically benefit manufacturers and sellers of
drugs and medical devices. Some of these defenses are also beginning to expand outside the realm of medical
products and are being applied to other sophisticated products as well.
1.Learned Intermediary Doctrine
Currently, perhaps the most important defense is the learned intermediary or sophisticated purchaser doctrine, mentioned above, which recognizes that it is usually an intermediary, not the manufacturer,
who plays the primary role in providing prescription products to users. For example, because drugs and medical devices interact with each individual’s body, it is the physician, not the manufacturer, who is in the best
position to determine which course of treatment is best suited to a particular patient’s needs. At the same
time, because of the complexity of medical products and the side effects and risks inherent in all such products, it is the physician, not the patient, who is in the best position to assess the specific risks to the patient
and to weigh those risks against the expected benefits. Moreover, from a practical standpoint, the manufacturer does not have contact with the user and cannot discuss the risks and benefits.
Therefore, the learned intermediary doctrine provides for an exception to the general rule in products liability that the manufacturer directly warn the consumer regarding the risks of the manufacturer’s
products. In re Norplant Contraceptive Prods. Liability Litig., 215 F. Supp. 2d 795, 803, 806-10 (E.D. Tex. 2002)
(analyzing law of all fifty states). Under this doctrine, the manufacturer of a medical product has a legal duty
to provide a warning to prescribing or treating physicians regarding products that require the assistance of a
physician to obtain. See Coyle v. Richardson-Merrell, Inc., 584 A.2d 1383, 1287 (Pa. 1991) (“a prescription drug
[is] a product whose distribution is limited precisely because its benefits and risks are to be assessed only by
licensed physicians acting on behalf of particular patients whose individual physical condition and circumstances are known to them”). If the manufacturer warns the prescribing physician (the learned intermediary)
of those risks that are known or reasonably scientifically knowable, there will be no failure to warn liability.
This is true even if the intermediary does not pass the warnings along to the users.
Some exceptions to the rule have developed on a case-by-case basis. The first such exception involved
vaccines used in mass immunizations, when it became apparent that physicians were vaccinating everyone
without truly exercising medical judgment about the risks. The second is in the case of oral contraceptives,
which by FDA regulation, require patient warnings.
More recent years have seen an expansion in “direct-to-consumer” (DTC) advertising, where manufacturers use television commercials and newspaper and magazine ads of general circulation to tout their
products. New Jersey has recognized DTC advertising as a circumstance that removes a product from the
learned intermediary rule. See Perez v. Wyeth Labs. Inc., 734 A.2d 1245, 1257-59 (N.J. 1999) (holding that
when pharmaceutical companies employ DTC advertising, there is an additional duty to warn consumers of
potential risks); New Jersey Citizen Action v. Schering-Plough Corp., 842 A.2d 174, 177 (N.J. Super. Ct. App.
Div. 2003), cert. den. 837 A.2d 1092 (N.J. 2003). In addition to New Jersey, West Virginia has refused to apply
the learned intermediary doctrine, citing DTC advertising as one reason to do so. See Johnson & Johnson Corp.
v. Karl, 647 S.E.2d 899, 907-11 (W. Va. 2007).
At the time of the Karl decision, New Jersey and West Virginia were stark outliers in this regard. See
generally Beale v. Biomet, Inc., 492 F. Supp. 2d 1360, 1376 (S.D. Fla. 2007) (applying Florida law) (“[i]t is now
eight years since Perez was decided, and no other state has followed suit”). Since Karl, though, attempts have
continued to chip away at the defense. For example, another court rejected the learned intermediary doctrine,
finding it “outdated” in a time of lay consumers serving as “do it yourself doctors.” Rimbert v. Eli Lilly & Co.,
577 F. Supp. 2d 1174, 1217-18 (D.N.M. 2008) (applying New Mexico law).
Then, in 2010, a Texas appellate court cited heavily to Perez and Karl in holding that “changes in the
delivery of healthcare brought about by direct marketing and managed care demonstrate that the theoretical
underpinnings of the ‘learned intermediary’ doctrine do not apply when a drug manufacturer directly markets to its consumers, the patients.” Centocor, Inc. v. Hamilton, 310 S.W.3d 476, 507-08 (Tex. App. 2010). The
Supreme Court of Texas reversed that decision and rejected any generally applicable DTC exception, while
also broadly and unequivocally embracing the learned intermediary’s continuing viability. See Centocor, Inc. v.
Hamilton, 372 S.W.3d 140 (Tex. 2012) (“The underlying rationale for the validity of the learned intermediary
doctrine remains just as viable today as stated by Judge Wisdom in 1974.”).
Subsequent courts, relying on Hamilton, continue to apply the learned intermediary doctrine. See,
e.g., McKay v. Novartis Pharm. Corp., 934 F. Supp. 2d 898, 910 (W.D. Tex. 2013) (acknowledging that the Centocor court declined to create a DTC exception); Saavedra v. Eli Lily & Co., 2013 WL 6345442 (C.D. Cal. Feb.
26, 2013) (holding that the doctrine applies to claims brought under the consumer protection laws of multiple
states); Seifried v. Hygenic Corp., 410 S.W.3d 427, 432 (Tex. App. 2013) (applying the doctrine to a hospital
overseeing a physical therapy regimen. Comment (e) to section 6 of the Restatement (Third) recognizes the
DTC issue but makes no recommendation, leaving it to developing case law.
Clearly, the learned intermediary and sophisticated purchaser doctrines provide tremendous benefits to manufacturers that provide comprehensive warnings. A warning may be adequate as a matter of law
and establishing such adequacy is generally easier under the learned intermediary doctrine. In that circumstance, adequacy is measured against what a trained physician could be expected to understand, not what
the patient would understand. See Mazur v. Merck & Co., 964 F.2d 1348, 1367 (3d Cir. 1992), cert. denied 506
U.S. 974 (1992) (applying Pennsylvania law) (the “intended audience is not the ultimate user, but rather the
learned intermediary”). Generally recognized elements to establish adequacy include whether the warning
(1) provides specific, detailed information about the particular risk or adverse medical outcome about which
the plaintiff complains, (2) describes the degree and seriousness of the danger accurately and with appropriate
intensity, (3) if applicable, alerts physicians to how they may avoid the risk or detect an adverse reaction at an
early stage, and (4) conveys its information in a satisfactory format, typically as dictated by the FDA.
Aside from adequacy, the existence of a learned intermediary can also benefit manufacturers that do
not include a particular warning because the learned intermediary rule can also lead to a failure of proof on
causation. For example, the manufacturer need not warn of risks that are known to the medical community. If
the intermediary acknowledges that the particular risk was known to him, even though the manufacturer did
not warn of the risk, there is no basis for liability. Considering their training and experience, physicians are
likely to have prior knowledge of information that is known throughout the medical profession. See, e.g., Lindsay v. Ortho Pharm. Corp., 637 F.2d 87, 92 (2d Cir. 1980) (applying New York law). Similarly, if the prescribing physician would have continued to prescribe the medication for the patient even if he had been provided
with the allegedly adequate warnings, the causal chain is broken. See, e.g., Carter v. Danek Med., Inc., No. CIV.
96-3243-G, 1999 WL 33537317, at *9 (W.D. Tenn. June 3, 1999) (applying Tennessee law).
2. Comment k
Another important defense applicable to prescription drugs and medical devices is set forth in comment k to section 402A of the Restatement (Second) of Torts. That comment, which discusses the applicability
of strict liability principles to what it terms “unavoidably unsafe products,” states:
There are some products which, in the present state of human knowledge, are quite incapable of
being made safe for their intended and ordinary use. These are especially common in the field of
drugs . . . . Such a product properly prepared, and accompanied by proper directions and warning, is not defective, nor is it unreasonably dangerous. The same is true of many other drugs,
vaccines, and the like, many of which for this very reason cannot legally be sold except to physicians, or under the prescription of a physician.
Restatement (Second) of Torts: Products Liability, §402A, comment k.
The most common example of an “unavoidably unsafe” product is a vaccine. For most vaccines, some
small portion of the population will either contract the disease being vaccinated against or suffer some severe
side effect. However, vaccines are so valuable to society as a whole, and the percentage of adverse effects so
small in comparison to the benefits, that it is important to have vaccines available. Moreover, no vaccine can
be made perfectly safe.
The California Supreme Court adopted comment k in 1988 in Brown v. Superior Court, 751 P.2d 470
(Cal. 1988). Although prior California decisions had expressed acceptance of comment k on a case-by-case
basis, the Brown court instead held that, for all prescription drugs, there can be no claim of strict liability for a
design defect. The decision was based on public policy grounds, largely a concern that the costs of strict liability would deter research and development and would drive the price of drugs so high that many needed drugs
would be beyond the reach of most consumers. The rule was also based on a recognition that each individual
reacts somewhat differently to a prescription drug, which must interact with systems poorly understood by
science. In that sense, prescription drugs were justifiably treated differently than products like wheelchairs.
After Brown, a number of appellate courts extended the comment k rationale to include all implanted
medical devices, which were considered sufficiently similar to prescription drugs in their interaction with the
body to warrant similar protections. See, e.g., Artiglio v. Superior Court, 27 Cal. Rptr. 2d 589 (1994) (silicone
gel breast implants). Thus, under comment k, as long as prescription drugs and devices are properly manufactured and accompanied by proper warnings, they cannot be held “defective” in design simply because their
use is attended by known but unavoidable risks.
By the early 1990s, though, while some courts followed Brown, a majority rejected blanket immunity
for all prescription products. See, e.g., Adams v. G.D. Searle & Co., 576 So. 2d 728 (Fla. Dist. Ct. App. 1991).
Instead, those courts allow liability for design defects in prescription products and view those products as
presumptively subject to the same design defect analysis applied to other products, unless the manufacturer
establishes as an affirmative defense that (1) the product could not be made safe, and (2) the product’s benefits outweigh its risks. Accordingly, while comment k expressly recognizes that a special test applies to prescription drugs, courts vary in how they implement that test and the majority approach – applying comment
k as an affirmative defense – may make it easier for a pharmaceutical manufacturer to defeat plaintiff ’s prima
facie case, in which plaintiff bears the burden of proof, than attempt to avail itself of proving that comment k
applies.
Interestingly, the Third Restatement eliminates comment k. Instead, the new Restatement creates a
special definition of design defect, which applies only to prescription drugs and medical devices and states
that such products are defective in design only where a reasonable health care provider, aware of all known
and knowable risks, would not prescribe the product for any class of patients. As this is a significant restriction on the concept of design defect, it appears at first glance to be an improvement on comment k. Courts,
however, have not greeted the Third Restatement view with open arms.
3. Federal Preemption
One defense in drug and device litigation that has significantly changed in recent years is the doctrine of federal preemption. In order to understand the significance of the defense, it is necessary to discuss it
as it applies to devices versus prescription drugs.
Device Preemption. Before 1976, medical devices were essentially unregulated. In that year, Congress
passed the Medical Device Amendments (MDA) to the Food, Drug, and Cosmetic Act. The MDA established
a classification system for medical devices, in which devices are placed into one of three groups, depending on
the degree of risks associated with the device and the amount of regulatory oversight required.
Class I devices are those where general FDA controls are sufficient to ensure safety and efficacy. They
are neither life-supporting nor life-sustaining, and do not present an unreasonable risk of illness or injury.
General controls include good manufacturing practices (GMP) regulations and labeling requirements. Examples of Class I devices are tongue depressors and crutches.
Class II devices are those where special FDA controls are needed to establish safety and efficacy,
but where special controls exist that can provide such assurances. These devices may or may not be life-supporting or life-sustaining. Such controls might include performance standards and post-market surveillance
requirements. Examples of Class II devices are tampons and external defibrillators.
Class III devices are either life-supporting and life-sustaining or they are for a use that is of substantial importance in preventing impairment of health or they present an unreasonable risk of injury or illness.
Examples include internal defibrillators and heart valves.
In addition to creating the classification system, the MDA described three ways by which a medical
device can reach the market. First, medical devices already on the market at the time of the MDA were grandfathered, meaning that they could remain on the market until such time as the FDA required proof of their
safety and efficacy.
Second, new devices that are “substantially similar” to devices already on the market are subject only
to a “pre-market notification process” in which the manufacturer demonstrates that the device is substantially
equivalent to an existing device. The pre-market notification process is described in §510(k) of the MDA, and
such devices are commonly called “510(k)” devices. The device being relied upon as a basis for clearance,
called the “predicate device,” can be a grandfathered device.
Third, new devices that are not substantially equivalent to existing devices are required to undergo
the most rigorous process, called pre-market approval (PMA). The PMA process requires that manufacturers
submit detailed information about design, manufacturing, and testing to demonstrate the device’s safety and
efficacy. Each application is referred to an FDA expert, and the FDA can spend as many as 1200 hours on a
single PMA.
The MDA also included a “preemption” provision, stating that no state could impose requirements
on medical device manufacturers that were “different from, or in addition to” the requirements imposed by
the federal government. This preemption language led manufacturers to argue that, through this provision,
Congress expressed an intent to occupy the entire field of legislation. Therefore, state tort laws could not apply
to medical devices because those tort laws were requirements “in addition to” requirements imposed by the
FDA. The circuit courts and the various state courts were split on the extent to which the MDA preempted tort
claims.
The issue was partly resolved by the United States Supreme Court in Medtronic, Inc. v. Lohr, 518
U.S. 470 (1996). There, the manufacturer of a pacemaker approved through the 510(k) process secured summary judgment on grounds of federal preemption. The issue divided the Supreme Court, resulting in only
a plurality decision. Ultimately, the plurality examined the regulatory process and the extent of review and
oversight given to the various types of new devices. The Court held that, unlike PMA devices, 510(k) devices
are reviewed not for safety and efficacy, but only for similarity to existing devices. The FDA is therefore not
imposing safety requirements on 510(k) devices, meaning that state tort laws imposing such requirements are
not different from, or in addition to federal requirements. Preemption was therefore not applicable to 510(k)
devices.
Lohr left undecided the applicability of preemption to PMA devices, which undergo rigorous FDA
review. Then, in Riegel v. Medtronic, Inc., the Supreme Court resolved that issue and held that all common law
tort claims relating to the “safety or effectiveness” of PMA devices are expressly preempted. 552 U.S. 312, 328
(2008). The Court specifically declined to address “parallel claims” or “claims premised on a violation of FDA
regulations.” Id. at 330. How plaintiffs frame such claims and whether parallel claims are preempted as well
are key issues regarding PMA devices post-Riegel.
After Riegel, courts around the nation dismiss design- and warnings-based claims involving PMA
devices, as well as implied-warranty claims. See Wolicki-Gables v. Arrow Int’l, Inc., 634 F.3d 1296 (11th Cir.
2011); In re Medtronic, Inc. Sprint Fidelis Leads Prods. Liab. Litig., 623 F.3d 1200, 1206 (8th Cir. 2010). As
a general principle, these courts require that plaintiffs support alleged parallel claims by adequately pleading, and providing evidentiary support of, violations of FDA standards. See id.; see also Funk v. Stryker Corp.,
631 F.3d 777, 782 (5th Cir. 2011); but see Bass v. Stryker Corp., 669 F.3d 501 (5th Cir. 2012). One appellate
court expressly links a parallel claim to the presence of a device-specific performance standard. See Walker v.
Medtronic, Inc., 670 F.3d 569 (4th Cir. 2012). Other courts are more lenient and require only minimal pleading
of the parallel claim. See Bausch v. Stryker Corp., 630 F.3d 546, 558 (7th Cir. 2010) (allowing a manufacturing
claim to proceed). While the standards vary some, Riegel preemption is so well established now that as a procedural matter, it typically arises at the pleadings stage rather than at summary judgment. It thereby offers the
potential to significantly lessen discovery and litigation costs.
Neither Lohr nor Riegel covered express warranty claims. Courts were split before Riegel and the split
continues after Riegel. Compare In re Medtronic, Inc. Sprint Fidelis Leads Prods. Liab. Litig., 592 F. Supp. 2d
1147, 1164 (D. Minn. 2009) (express warranty claims preempted) with Delaney v. Stryker Orthopaedics, No.
08-3210 (DMC), 2009 WL 564243, at *5 (D.N.J. Mar. 5, 2009) (express warranty claims not preempted).
The Ninth Circuit addressed the issue of parallel claims in Stengel v. Medtronic, Inc., 704 F.3d 1224
(9th Cir. 2013). In Stengel, the court concluded that the MDA does not preempt a state-law claim in which the
state-law duty of care “parallels” a federal-law MDA duty. There, the manufacturer of an FDA-approved device
allegedly failed to notify the FDA of risks associated with the device that were discovered post-approval. In
addition to the MDA’s requirement to notify the FDA of such risks, the court concluded that the applicable
state consumer protection laws also included a duty to warn the FDA of subsequently identified risks. Because
the state law imposed no different or additional duty on the manufacturer, the court found that the state-law
duty was parallel to the federal duty. Therefore, the state-law failure-to-warn claim was not preempted by the
MDA.
Off-label use, or using a device in a manner that was not approved by the FDA, should not preclude
the preemption of claims involving PMA devices under Riegel, particularly because Riegel involved an off-label
use. See Riegel v. Medtronic, Inc., 128 S.Ct. 999, 1005 (2009) (device employed in diseased and calcified artery,
despite contraindication of such use, and device was inflated beyond rated burst pressure). Other courts have
applied Riegel preemption to off-label uses. Blankenship v. Medtronic, Inc., 2014 U.S. Dist. LEXIS 39063, **1131 (E.D. Mo. Mar. 25, 2014); Wolicki-Gables v. Arrow Int’l, Inc., 641 F. Supp. 2d 1270, 1284-88 (M.D. Fla. 2009).
Courts vary in applying Riegel preemption to off-label marketing claims. See, e.g., Scovil v. Medtronic,
Inc., 2014 WL 502923 (D. Ariz. Feb. 7, 2014) (applying Riegel preemption and finding that some of plaintiffs’ claims survived the preemption analysis); Ledet v. Medtronic, Inc., 2013 WL 6858858 (S.D. Miss. Dec.
30, 2013) (applying Riegel preemption and finding that plaintiffs’ claims were preempted because the state
requirements were “in addition to” the requirements imposed by federal law); Ramirez v. Medtronic Inc., 961
F. Supp. 2d 977 (D. Ariz. 2013) (finding that the Riegel analysis of whether state-law claims qualify as parallel claims did not apply to claims of off-label marketing and those claims were not preempted); Caplinger v.
Medtronic, Inc., 921 F. Supp. 2d 1206, 1215 (W.D. Okla. 2013) (applying Riegel and finding that the plaintiff ’s
claims were preempted).
Another court found that off-label promotion claims could escape preemption where a violation of
federal law was combined with a state-law claim alleging inadequate warnings or other false information. See
Houston v. Medtronic, Inc., 957 F. Supp. 2d 1166, 1179-80 (C.D. Cal. 2013). The court explained that there was
no likelihood that the manufacturers could be held liable under state law without having violated the federal
law prohibiting off-label promotions. Therefore, the fraud claims were parallel or “genuinely equivalent” to
federal law.
Drug Preemption. Unlike medical devices, no express preemption provision arises under the FDCA
for prescription drugs or biological products. See Abbott v. Am. Cyanamid Co., 844 F.2d 1108, 1111 (4th Cir.
1988) (finding no express preemption provision applicable to biologics); Eve v. Sandoz Pharm. Corp., 2002
WL 181972, at *1 (S.D. Ind. 2002) (“The portion of the FDCA that is applicable to drugs does not contain a
preemption provision.”). As a result, the key preemption issue concerning prescription drugs revolves around
implied preemption or, more specifically, implied conflict preemption (field preemption has never applied to
FDA regulation of drugs or medical devices).
Conflict preemption arises “where it is impossible for a private party to comply with both state and
federal law” or where state law “stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress.” Crosby v. Nat’l Foreign Trade Council, 530 U.S. 363, 372-73 (2000). Preemption is not limited to state statutes, but also includes state law tort obligations such as those imposed by jury
verdicts in drug and device cases. Likewise, preemption does not require a federal law to conflict with the
state law or obligation, but federal regulations, such as those enacted by the FDA, “have no less pre-emptive
effect than federal statutes.” Fidelity Fed. Sav. & Loan Ass’n v. de la Cuesta, 458 U.S. 141, 153 (1982). Essentially, conflict preemption arises in the drug and device realm when FDA regulations compel a manufacturer
to take certain actions – requiring certain warnings, manufacturing or design processes, etc. – while a jury
determines that the manufacturer should have acted differently and imposes liability under state tort law.
Hence, the “impossibility” of complying with both state and federal law.
The U.S. Supreme Court examined preemption of warnings-based prescription drug claims in Wyeth
v. Levine, 129 S.Ct. 1187 (2009). In Levine, the Court ruled that FDA approval of drug labeling does not have
a broad preemptive effect. Rather, the “central premise of federal drug regulation [is] that the manufacturer
bears responsibility for the content of its label at all times.” Id. at 1197-98. As a result, claims under state tort
law were not impliedly preempted.
Nonetheless, the Court did not eliminate preemption under all circumstances. Instead, the Court
concluded with the “recogni[tion] that some state-law claims might well frustrate the achievement of congressional objectives.” Id. at 1204. Defendants may still pursue preemption by presenting “clear evidence that the
FDA would not have approved a [label] change” of the type alleged by the plaintiff. Id. at 1198. After Levine,
preemption of prescription drug claims is a highly drug-specific and fact-specific defense. The regulatory facts
for the product at issue will drive the analysis. Key points may include whether the FDA specifically considered and rejected a stronger warning and whether significant new data or risk analysis existed after the FDA’s
last assessment of the product. See generally Lofton v. McNeil Consumer & Specialty Pharm., 682 F. Supp. 2d
662, 678 (N.D. Tex. 2010) (recognizing what the court deemed a “limited exception” under Levine that preempts claims when “the evidence shows that the FDA would have rejected adding [the] specific medical conditions to the [product’s] label.”).
After Levine, courts have denied many preemption arguments, especially absent evidence showing
specific FDA evaluation and action relative to the particular risk at issue. See Mason v. SmithKline Beecham
Corp., 596 F.3d 387, 394 (7th Cir. 2010). Defendants have failed to satisfy the “clear evidence” requirement
by showing that the FDA would “prohibit all enhanced warnings,” see Forst v. SmithKline Beecham Corp., No.
07-CV-612, 2009 WL 2256232, at *4-*5 (E.D. Wis. July 29, 2009), when insufficient evidence existed that the
FDA specifically evaluated and acted upon the particular risk alleged, see Schrock v. Wyeth, Inc., 601 F. Supp.
2d 1262, 1265-66 (W.D. Okla. 2009), and when the FDA later approved the same warning that the plaintiff
alleged should have been given, see Brockert v. Wyeth Pharm., Inc., 287 S.W.3d 760, 768-69 (Tex. App. 2009). It
remains to be seen whether further developments in the case law might expand the limited confines of Levine
preemption. See generally Robinson v. McNeil Consumer Healthcare, 615 F.3d 861, 873 (7th Cir. 2010) (recognizing FDA action as preemptive when “[t]he FDA decided not to require such a warning because it would
confuse rather than inform; and a court cannot order a drug company to place on a label a warning if there is
‘clear evidence’ that the FDA would not approve it.”).
On the positive side already, “clear evidence” resulting in preemption existed when FDA rejected a
pre-approval supplement concerning the same risk claimed by the plaintiff and under the same standard of
scientific evidence used to determine whether a CBE submission is required. See In re Fosamax Prods. Liab.
Litig., 951 F. Supp. 2d 695 (D.N.J. 2013). The holding here is proof that valid preemption arguments still exist
in cases with a sufficiently favorable regulatory history. See also Dobbs v. Wyeth Pharm., 797 F. Supp. 2d 1264
(W.D. Okla. 2011) (FDA denied that sufficient scientific evidence supported a warning).
While Levine covers preemption for name-brand products, the preemption of claims against generic
products is governed by PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011). In Mensing, the Court held that warning-related claims against generic drugs conflict with federal law and are preempted. The Court based its
reasoning on the unique regulatory environment that applies to generic drugs under the Hatch-Waxman
amendments to the FDCA (formally titled the “Drug Price Competition and Patent Term Restoration Act of
1984,” Pub. L. No. 98-417, 98 Stat. 1585). See Mensing, 131 S. Ct. at 2574-75. Generic drugs “gain FDA approval
simply by showing equivalence to a [brand-name] drug that has already been approved by the FDA.” Id. at
2574 (citing 21 U.S.C. §355(j)(2)(A)); see also 21 C.F.R. §314.127(a)(7).
That showing of equivalence includes all labeling information. See id. The generic manufacturer’s
obligation is summarized as the “responsib[ility] for ensuring that its warning label is the same as the brand
name’s.” Id. at 2574 (citing 21 U.S.C. §355(j)(2)(A)(v), §355(j)(4)(G); 21 C.F.R. §314.94(a)(8), §314.127(a)(7)).
As a result, “generic drug manufacturers have an ongoing federal duty of ‘sameness.’” Id. at 2575. That duty of
sameness results in preemption:
We find impossibility here. It was not lawful under federal law for the [m]anufacturers to do
what state law required of them. . . .
If the [m]anufacturers had independently changed their labels to satisfy their state-law duty,
they would have violated federal law. Taking [plaintiff ’s] allegations as true, state law imposed on
the [m]anufacturers a duty to attach a safer label to their generic [drug]. Federal law, however,
demanded that generic drug labels be the same at all times as the corresponding brand-name
drug labels. Thus, it was impossible for the [m]anufacturers to comply with both their state-law
duty to change the label and their federal law duty to keep the label the same.
Id. at 2577-78 (citing 21 C.F.R. §314.150(b)(10)).
After Mensing, warning-related claims involving generic drugs are broadly preempted. See Smith v.
Wyeth, Inc., 657 F.3d 420 (6th Cir. 2011); In re Accutane Prods. Liab., No. 8:04–MD–2523–T–30TBM, 2011
WL 6224546 (M.D. Fla. Nov. 9, 2011). Some outlier cases existed, most notably on design-defect claims.
See Bartlett v. Mut. Pharm. Co., 678 F.3d 30 (1st Cir. 2012). In Bartlett, the First Circuit held that Levine, not
Mensing, controlled the analysis and rejected preemption because the manufacturer had the option of choosing not to manufacture and market the drug at all.
More recently, though, the Court reversed that decision and ruled that the labeling protections for
generic makers in Mensing applied to the design-defect complaint as well. Mut. Pharm. Co. v. Bartlett, 133 S.
Ct. 2466, 2480 (2013). The Court explained that under New Hampshire’s strict products liability law a drug
manufacturer must ensure that its products are not “unreasonably dangerous,” and that the manufacturer
could satisfy that duty either by changing a drug’s design or changing its labeling. However, federal law prohibited the manufacturer from changing the drug’s design, so New Hampshire law effectively required the
manufacturer to change the drug’s labeling. Because Mensing prevents generic-drug manufacturers from
changing their drug labels, federal law prohibited the manufacturer from taking the required state-law remedial action to avoid liability. Thus, federal law preempted both state-law duties. Id.
Subsequent courts have adhered to this standard. See, e.g., Lashley v. Pfizer, Inc., 750 F.3d 470, 475
(5th Cir. 2014) (finding that non-failure-to-warn claims, such as those based on strict liability and breach of
warranty theories, are preempted under Mensing and Bartlett); Drager v. PLIVA USA, Inc., 741 F.3d 470, 477
(4th Cir. 2014) (confirming that negligence claims are preempted when a generic drug manufacturer could
not satisfy a duty to protect the consumer without changing its warnings, changing its formulation, exiting
the market, or accepting tort liability); Strayhorn v. Wyeth Pharm., 737 F.3d 378 (6th Cir. 2013) (design-defect
claims based on consumer expectations are preempted because prescribers rely upon warnings to form expectations); Schrock v. Wyeth, Inc., 727 F.3d 1273, 1276 (10th Cir. 2013) (applying Mensing and Bartlett to hold
that a consumer’s breach of warranty claims were preempted).
4.State of the Art
Another defense utilized by manufacturing defendants is an argument that, at the time of sale, the
product was the “state of the art:” that is, the best that technology permitted at the time. With respect to warning defects, the “state of the art” concept is implicit in the requirement that plaintiffs prove the risk was known
or reasonably scientifically knowable. With respect to manufacturing defects, the defense will typically not
come into play because such defects arise from a flaw in the manufacturing process that affects only certain
units; it is difficult to argue that the defective unit was the state of the art when the same process yielded nondefective units.
Finally, as for design defects, state of the art evidence is admissible to show that there was no feasible,
safer alternative design. Some jurisdictions require by statute that the jury consider the state of the art at the
time of manufacture. See generally Fla. Stat. Ann. §768.1257. Although evidence of industry custom is relevant
and admissible, it is not dispositive, and the jury is entitled to find an entire industry lacking. Comment d to
section 2(b) of the Third Restatement, which addresses general design defects concepts, discusses “state of the
art” evidence as relevant to the design defect issue.
5.Bulk Supplier Defense
Parties who supply raw materials in bulk, and who have no control over generally subsequent compounding, packaging, or marketing of the finished product are not liable for injuries resulting from use of the
finished product. Artiglio v. GE, 61 Cal. App. 4th 830 (1998) (supplier of raw silicone used in breast implants);
Walker v. Stauffer Chem., 19 Cal. App. 3d 669 (1971) (bulk supplier of chemicals).
F. Glossary of Key Terminology
ANDAAbbreviated New Drug Application. The means by which a generic manufacturer seeks approval from the FDA to market a generic drug. The ANDA process requires that generic products are identical to brand-name products both
pharmacologically and in labeling.
Banned DevicesA device that the FDA prohibits for human use due to an unreasonable or substantial risk of illness or injury. A device may also be banned by the FDA if the
device presents a substantial deception that the manufacturer does not correct
after a request by the FDA.
Brown
The California Supreme Court opinion that adopted comment k in California.
C.F.R.Code of Federal Regulations. Section 21 sets forth extensive regulations governing medical devices.
Devices for which “general controls” reasonably assure safety and effectiveClass I Devices
ness; Class I devices are neither life-supporting nor life-sustaining; they are
not of substantial importance in preventing impairment of health; and they
do not present a potential unreasonable risk of illness or injury. Many Class
I devices are exempt from premarket notifications and good manufacturing
practices because of their low risk.
Devices for which Class I controls are inadequate and there is sufficient inforClass II Devices
mation to show that “special controls” are needed to provide a reasonable
assurance of same and effective use. Class II devices may include life-sustaining and life-supporting products. The FDA examines and identifies the special controls that are necessary to provide an adequate assurance of safety and
effectiveness for such devices.
Devices for which there is insufficient information to show that Class I conClass III Devices
trols or Class II controls can provide a reasonable assurance of safety or effectiveness. These devices include life-supporting and life-sustaining devices,
devices of substantial importance in preventing impairment of human health,
and devices that present a potentially unreasonable risk of illness or injury.
These devices are subject to product-by-product PMA review.
An FDA-regulated process for testing medicine and products to determine
Clinical Trial
their safety and efficacy.
Comment k
Refers to a subsection of the Restatement of Torts 2d, section 402a, which
states that due to the unavoidably unsafe nature of prescription drugs, they
should not be subject to strict liability for design defects.
A manufacturer of a device is required to keep all records of all information
Complaint Files
received for which an MDR was required. These records are subject to FDA
inspection without notice.
Letters sent by the manufacturer to doctors advising or warning them of a
“Dear Doctor” Letters
particular situation or problem with a product.
Design Defect
Whether a product was reasonably designed to prevent foreseeable injuries.
This defect is generally present in every unit of the product, even though it
does not cause injury to every user.
Sales representatives who visit doctors or hospitals to promote or demonstrate
Detailers
products.
Device User Facility Reports
A hospital, outpatient facility, or similar facility must notify the FDA when
information reasonably suggests that a device used at the facility has or may
have caused or contributed to death or serious injury to a patient.
When scientific evidence indicates that the appropriate use of the device will
Efficacy
produce clinically significant results in a significant portion of the target population. 21 C.F.R. 5870.7(3)(1).
The Food and Drug Administration. The federal agency that controls the
FDA
development, testing, manufacture, approval, and sale of drugs and devices.
FDCA
Federal Food, Drug and Cosmetic Act, 21 U.S.C. 5321 et seq.; the federal law
that controls the development, testing, approval and sale of drugs and devices;
medical devices were not specifically covered until the Medical Device
Amendments of 1976.
Freedom of Information Act. Anyone can request from the FDA information
FOIA
about devices, including information about adverse reactions, and so forth by
sending a letter to the FDA. This is a popular source of information for plaintiffs.
The liability of manufacturers of prescription products for a failure to warn is
Failure to Warn
generally determined under a negligence-like standard. Under that standard,
a manufacturer must warn of all known or scientifically knowable side effects
and adverse reactions.
GLP
Good laboratory practice regulations
GMP
Good manufacturing practice regulations
Grandfathered Devices
Devices that were on the market prior to 1976, when the federal government
first began regulating medical devices, and were allowed to remain on the
market unless and until the FDA requested evidence of safety and efficacy.
Investigational Device Exemption. A means by which a device being experiIDE
mented for safety and efficacy may be marketed on a limited basis to further
the investigation process.
Investigational New Drug Application. A means by which a device being
IND
experimented for safety and efficacy may be marketed on a limited basis to
further the investigation process.
Institutional Review Board. The group within a hospital that oversees clinical
IRB
trials being performed in that facility. The IRB typically determines whether
the facility will participate in the trial, what the informed consent documents
will look like, whether the protocol is being followed, and so forth.
Device placed into the human body and intended to remain for 30 days or
Implanted Device
more. 21 C.F.R. 5860.3(d).
Inspection
The FDA has the right—exercised at least once every two years—to inspect
the facilities of each manufacturer or processor of Class II or III devices.
Learned Intermediary
Generally for prescription medical products, the manufacturer has a duty
to warn the physician, not the patient, of known or reasonably scientifically
knowable risks. There is no duty to warn the patient directly. There is an analProducts Liability: Claims, Defenses, and Case Handling ■ Gerecke and Walz ■ 37
ogous doctrine for other products that are sold to a sophisticated purchaser,
which lessens the extent of warning required.
MDA
Medical Device Amendments of 1976 to the FDCA. The first statutory authority regarding government regulation of medical devices.
MDR
Medical Device Reports; now officially called Medwatch (FDA Form 3500
and 3500A). A manufacturer must submit a report to the FDA if it receives
or becomes aware of an incident where its device caused or contributed to a
death or serious injury or a device malfunctioned and if a recurrence of the
malfunction would likely cause or contribute to death or serious injury.
A product that differs from the manufacturer’s intended result, that is, the
Manufacturing Defect
product was not made according to specifications. Unlike design defect, this
typically affects only one unit or one lot of the product and not the entire
product line.
Instruments, implements, machines, and other things that are intended for
Medical Device
use in diagnosing or treating diseases or other conditions, or that are intended
to affect the body’s structure or function.
The 2011 Supreme Court case that controls preemption of warning-related
Mensing
claims against generic manufacturers.
Misbranding
False, misleading, or inadequate labeling of a device.
NDA
New Drug Application. The means by which a manufacturer seeks approval
from the FDA to market a new prescription drug.
OTC
Over the Counter. A drug or device that may be sold without a prescription.
Off-Label Use
Medical products are approved by the FDA for specific uses. A doctor or hospital using the product for other uses is an off-label use. It is neither illegal nor
even necessarily negligent for a doctor or hospital to engage in such conduct.
It is illegal, however, for a manufacturer to promote or encourage an off-label
use.
Premarket Approval. The most complicated means of getting a new medical
PMA
device to market. This procedure requires several phases of dinical trials as
well as a lengthy application and review process. It has been estimated that
a PMA review by the FDA can take up to 1,200 hours. Preemption of claims
involving PMA devices applies under the 2009 decision in Riegel.
A document that accompanies a prescription device and that sets forth warnPackage Insert
ings and directions for use to the physician (sometimes there may also be a
package insert for the patient). The package insert generally contains information regarding indications and uses, contraindications, warnings, adverse
reactions, directions for use, and so forth.
A doctrine that may provide a complete defense. The doctrine applies when
Preemption
federal regulations specifically regulate a product, and precludes states from
creating legal requirements that are “different from, or in addition to,” the federal requirements.
Premarket Notification
Also known as a 510(k). A medical device can be marketed without the full
clinical trials and lengthy application required by the PMA process, if the
device is “substantially equivalent” to a device already being marketed. Products that have gone through the 510(k) process are “cleared for marketing”
rather than “approved.”
When scientific evidence indicates that the benefits of use with adequate
Safety
directions and warnings outweigh the probable risks. 21 C.F.R. §860.7(d)(1).
Serious Injury
An injury that is life threatening or results in permanent impairment or damage to the body.
Strict Liability
A party in the chain of distribution is held liable for defects in the product that
cause injury, regardless of the extent of care taken in producing or marketing
the product.
A device that is substantially equivalent to a device that was (1) distributed
Substantially Equivalent
prior to May 28, 1976, or (2) that has been classified as a Class I or H device.
21 C.F.R. §860.134. See also 510(k).
Unapproved use
See “Off-Label Use”
510(k)
Premarket Notification
II. The Restatement (Third)
An Update
A.Introduction
The Restatement (Third) of Torts: Products Liability (hereafter “Restatement Third”) was adopted in the
late 1990s in response to the courts’ varying approaches to products liability law, with some jurisdictions adhering to a strict liability theory while others to a negligence theory. These different approaches arise from the fact
that the “consumer expectation test” cannot be effectively used in all cases. For example, in cases involving prescription drugs or medical devices, the consumer would not know what to expect, because he would have no
idea how safe the product could be made. See Dart v. Wiebe Mfg., Inc., 709 P.2d 876 (Ariz. 1985). In those types of
cases, where the “consumer expectation test” is of little use, some jurisdictions adopted a “risk/benefit” analysis
to determine what constitutes a defective condition unreasonably dangerous. Id.
The Restatement Third sought to clarify some of the confusion in products liability law. See generally
Edward Gerecke, E. Kelly Bittick, Jr., and David Walz, Design Defects in Prescription Medical Products, For
the Defense 37 (April 2006) (discussion of section 6(c) of the Third Restatement and its adoption and treatment in various states).
Among the more controversial provisions of the Restatement Third are sections 2 and 6. Although
section 2 continues to recognize that a product is defective if it has a manufacturing defect, design defect,
or inadequate instructions or warnings, it changes the standard of liability for design defect and inadequate
warnings. Under section 2, strict liability claims for design defects and inadequate warnings now require a
showing of reasonableness and foreseeability, elements traditionally associated with a negligence theory.
Section 6 of the Restatement Third applies only to manufacturers of prescription drugs and medical
devices. It creates a stricter test for design defect by imposing liability for a prescription product only when
the “risks of harm so far outweigh its therapeutic benefits that reasonable, properly informed health care proProducts Liability: Claims, Defenses, and Case Handling ■ Gerecke and Walz ■ 39
viders would not prescribe it.” Restatement (Third) of Torts: Products Liability Section 6(c). Under section
6(c),”a drug is defectively designed only when it provides no net benefit to any class of patients.” Restatement
(Third) of Torts: Products Liability Section 6 cmt. b [emphasis added].
To assess the overall impact, if any, that the Restatement Third has had on drug and device cases, one
must look at how the courts have applied its various sections. The following is a summary of state and federal
court cases addressing the matter.
B. Section 2(b): Not Adopted in Green v. Smith & Nephew AHP, Inc., 629
N.W.2d 727 (Wis. 2001)
The plaintiff, a hospital worker, brought a products liability action against the manufacturer of latex
gloves alleging that the gloves were defective and unreasonably dangerous. The plaintiff sought damages for
an allergic reaction she allegedly suffered from exposure to latex. The trial court entered judgment in favor of
the plaintiff and the court of appeal affirmed. The Wisconsin Supreme Court granted review.
One of the issues on review was whether the trial court erred in instructing the jury that a product
can be deemed defective and unreasonably dangerous regardless of whether the manufacturer of that product
knew or could have known the risk of harm that the product presented to consumers. The court found that
the jury instruction was not erroneous and reaffirmed Wisconsin’s longstanding rule that foreseeability of the
risk of harm is not part of Wisconsin products liability law.
The defendant urged that the Wisconsin Supreme Court adopt the element of foreseeability as delineated in section 2(b) of the Restatement Third. The court refused to adopt this section because it contravened
Wisconsin law. Moreover, the court criticized section 2(b) because it creates a higher bar for recovery than
in comparable negligence. The court specifically rejected section 2(b) because it found that it further burdens consumers by requiring them to prove that there was a “reasonable alternative design” available to the
product’s manufacturer. According to the Wisconsin Supreme Court, this extra requirement contravenes the
policies underlying strict products liability law by requiring the plaintiff also to prove negligence. The court
refused to “impose such a burden on injured persons.” Id. at 824.
C. Section 6(b): Relied Upon in Stahl v. Novartis Pharmaceuticals Corp., 283
F.3d 254 (5th Cir. 2002)
The plaintiff developed cholestatic hepatitis after taking the drug Lamisil for the treatment of a fungal infection. The plaintiff filed a lawsuit in federal court against the drug manufacturer alleging the following
two claims under Louisiana products liability law: (1) that Lamisil is unreasonably dangerous in composition,
and (2) that Lamisil is unreasonably dangerous because an adequate warning had not been provided.
In affirming the trial court’s granting of summary judgment in favor of the defendant, the United
States Court of Appeals found that plaintiff had produced no evidence that Lamisil was unreasonably dangerous in composition. It further found that the defendant’s warnings about the risks associated with the drug
and the defendant’s medical monitoring instructions were adequate as a matter of law.
One issue raised on appeal was whether a failure to warn claim could be brought based on the adequacy of the medical monitoring instructions contained in the package insert. The defendant argued that
medical monitoring instructions are simply recommendations by the drug manufacturer and are not actually
“warnings” that can form the basis for a failure to warn claim. The court of appeals disagreed, and in so doing,
it relied on, among other things, section 6(b) of the Restatement Third. Id. at 269. That section provides that a
prescription drug or medical device is defective if it “is not reasonably safe due to inadequate instructions or
warnings.” Restatement (Third) of Torts: Products Liability §6(b).
D. Section 6(c): Not Adopted in Bryant v. Hoffman-La Roche, Inc., 582 S.E.2d
723 (Ga. App. 2003)
The plaintiff filed suit for strict liability and negligent design against the manufacturer of Posicor, a
heart drug that allegedly caused his wife to sustain brain damage and die. On appeal from summary judgment
for the defendant manufacturer, the plaintiff argued that there were factual issues as to whether Posicor was a
defective drug. The defendant urged that the court adopt the test for pharmaceutical design defect set forth in
section 6(c) of the Restatement Third.
The majority of the court expressly declined to adopt the standard set forth in section 6(c) because
there was no prior Georgia case law that would authorize its adoption. Id. at 406.
The concurring opinion, on the other hand, urged the adoption of section 6(c) because “prescription
drugs are a unique category of product” for which the test for general products under section 2 is unworkable.
Id. at 416. The court highlighted two important distinctions between the tests for design defect under section
2 and under section 6(c). First, section 2 imposes liability on a manufacturer if the manufacturer could have
developed a safer alternative design that would have prevented the injury but that design was not developed
or marketed. Section 6(c) does not permit this type of liability for prescription drug manufacturers because it
recognizes that no court could properly replicate the expensive and time-consuming FDA drug-approval process in a trial setting, a showing that would be necessary to prove the existence of a safer alternative.
A second important distinction between the two tests is that section 6(c) does not deem a prescription drug defective if it benefits any class of patients. This allows patients who benefit from the drug to continue to have access to the drug despite the fact that it may cause adverse reactions in others.
The concurring opinion further noted that although, to date, the test under section 6(c) has not been
adopted by any court, it is merely because courts have not had the opportunity to consider the new test as an
alternative. Id. at 416.
E. Section 6(c): Not Adopted in Freeman v. Hoffman-LaRoche, Inc., 618
N.W.2d 827 (Neb. 2000)
The plaintiff filed suit against the manufacturer of Accutane, claiming that she sustained personal
injuries while using the prescription acne medication. The defendant demurred to the plaintiff ’s seven-count
complaint, and the trial court sustained the demurrer and dismissed the plaintiff ’s complaint with prejudice.
On appeal from the trial court’s ruling, plaintiff argued that Accutane contained a design defect as
“the risks inherent in the design outweighed the benefits of its use.” The plaintiff also argued that Accutane
was more dangerous to her than she anticipated because of its undisclosed side effects. Id. at 556. Relying on
McDaniel v. McNeil Laboratories, Inc., 241 N.W.2d 822 (1976), and comment k, defendant argued that Accutane was exempt from liability for design defects because it was approved by the FDA.
The issue squarely before the Nebraska Supreme Court in Freeman was whether to accept the newly
formulated standard for design defects under section 6(c) of the Restatement Third. The Freeman court
declined to adopt section 6(c), criticizing the section on several grounds and stating that “Section 6(c) has no
basis in the case law” and it is “too strict a rule, under which recovery would be nearly impossible.” Id. at 567.
The court further rejected “blanket immunity” for prescription drug manufacturers under comment
k and in so doing overturned its prior decision in McDaniel. Instead, the court adopted a case-by-case approach
in which prescription drug manufacturers can raise comment k as an affirmative defense if they prove: “1) the
product is properly manufactured and contains adequate warnings; 2) its benefits justify its risks; and 3) the
product was at the time of manufacture and distribution incapable of being made more safe.” Id. at 568.
F. Section 6(c): Factual Record Precluded Decision in Hansen v. Baxter
Healthcare Corp., 764 N.E. 2d 35 (Ill. 2002)
The plaintiff filed a lawsuit alleging product liability against the manufacturer of an intravenous catheter connector. The plaintiff alleged that his wife suffered an air embolism and later died when her catheter
connection detached. The case came before the Illinois Supreme Court after the court of appeal affirmed a
trial court judgment for the plaintiff in the amount of $18 million (later reduced by partial set-off of settlement amounts.)
One of the issues before the Illinois Supreme Court was whether the court of appeal properly found
that there was sufficient evidence to justify the verdict based on defective design theory. The court refused to
address the applicability of the design defect test under section 6(c) because the defendant had not preserved
the issue for appeal. The court stated that application of this new test would require expert medical testimony
that was not proffered by any party. Although the court refused to apply section 6(c) for procedural reasons,
it did not foreclose the possibility of doing so in future cases. Specifically, the Illinois Supreme Court stated,
“We do not foreclose the consideration of the Restatement (Third) of Torts standard in another case where it is
raised at trial and appropriately briefed and argued.” Id. at 438.
G. Section 6(c): Not Adopted in Mele v. Howmedica, Inc., 808 N.E.2d 1026
(Ill. App. Ct. 2004)
The plaintiff sued Howmedica, Inc., the manufacturer of a medical device that a surgeon implanted
into his hip. Following a jury trial, judgment was entered in favor of the plaintiff awarding him $400,000 in
damages based upon a finding that Howmedica’s medical device was unreasonably dangerous and caused the
plaintiff ’s injury:
On appeal, Howmedica requested that the court consider the issue of determining whether the device
was, in fact, unreasonably dangerous through the guise of section 6(c). The manufacturer argued that the foreseeable therapeutic benefits from the use of the device are outweighed by the foreseeable risks of harm.
The court rejected this request on two grounds: First, this Restatement section completely eliminates
appraisal of the consumer’s expectations from determination of whether a medical device is unreasonably
dangerous. Thus, this section is in direct conflict with Illinois law. See Lamkin v. Towner, 138 Ill.2d 510, 529
(1990).
Second, the court rejected the request by the manufacturer to adopt section 6(c) because it tends to
provide virtual immunity from liability for all medical products. The court noted that it would be a rare occasion when a determination would be reached that a device would never prove useful for any patient. Thus, the
fact that the device remains useful for some patients would immunize the manufacturer from liability altogether. Based thereon, the court refused to adopt section 6(c).
H. Section 6(c): Adopted in Madsen v. American Home Products Corp., 477
F. Supp. 2d 1025 (E.D. Mo. 2007)
The plaintiff developed valvular heart disease allegedly caused by her use of Pondimin and Redux.
Along with failure-to-warn claims, plaintiff also alleged a design defect claim.
The court determined that, because Iowa law had previously adopted sections 1 and 2 of the Restatement (Third) of Torts for product defect cases in general, it would also apply the standard set forth in section
6(c). The court concluded that plaintiff failed to present a genuine issue of material fact under that standard
and awarded summary judgment. See id. at 1037. Specifically, the plaintiff did not present “any evidence that
reasonable health-care providers, knowing the risks and benefits, would not have prescribed the products to
any class of patients.” Id. In addition, plaintiff did not dispute the testimony from defendant’s expert that he
“would prescribe those medications for appropriate patients” and that plaintiff ’s prescribing physician continued to prescribe both products. Id. Thus, plaintiff could not meet the section 6(c) standard.
I. Section 6(c): Adopted in Harrison v. Howmedica Osteonics Corp., No. CIV
06-0745 PHX RCB, 2008 WL 906585 (D. Ariz. Mar. 31, 2008)
Defendant moved for summary judgment on the grounds that plaintiff lacked sufficient evidence to sustain his design defect claims. The court adopted the line of reasoning used in Gebhardt v. Mentor Corp., 191 F.R.D.
180, 185 (D. Ariz. 1999) (previously applying section 6(c) and granting summary judgment as a result), and held
that it would apply section 6(c) because Arizona state courts “demonstrated a willingness” to refer to other sections of the Restatement (Third). Harrison, 2008 WL 906585, at *22. The court then determined that plaintiffs
failed to show “that a reasonable health-care provider would not prescribe the [product] for any class of patients
and thus that the [product] was defectively designed.” Id. (emphasis in original) (quoting Gebhardt, 191 F.R.D.
at 185; citing Taylor v. Danek Med., Inc., 1998 WL 962062 (E.D. Pa. Dec. 29, 1998) (granting summary judgment
and using section 6(c) as an alternate source of reasoning)). Indeed, the court noted that the record evidence was
to the contrary because health-care providers, including plaintiff ’s operating physician, “would and continue to
use the [product] for patients who have sustained [injuries] such as that sustained by [plaintiff].” Id.
J. Section 6(c): Applied in Mills v. Bristol-Myers Squibb Co., No. CV
11-00968-PHX-FJM, 2011 WL 4708850 (D. Ariz. Oct. 7, 2011)
Plaintiff took Plavix, a drug designed to prevent blood clots, and aspirin daily for several days to treat
peripheral vascular disease. After five days, she began bleeding from her rectum. She eventually underwent
surgery and suffered several other health problems. She alleged strict liability based on failure to warn and
design defect. She alleged that Plavix was unreasonably dangerous because it carried a higher risk of adverse
health effects for patients who carry CYP, a genetic variant that makes carriers poor metabolizes of the drug.
The plaintiff alleged that about thirty percent of Caucasians carry CYP. Plaintiff alleged that she is a carrier of
CYP, although she had not been tested for it. She also alleged that Plavix carries a higher risk of bleeding complications for patients with peripheral vascular disease.
While plaintiff “allege[d] that no reasonable health-care provider would prescribe Plavix for plaintiff knowing the risks to ‘Caucasian patients who carry the genetic variant allele CYP who are poor metabolizers of Plavix, and who are diagnosed with peripheral vascular disease and concomitantly ingest Aspirin,’”
the court held that “the Restatement (Third) of Torts’ definition of an unreasonably safe prescription drug or
medical device [applies] to Arizona design defect claims.” Id. at *2-*3. Under the section 6(c) standard, such
allegations failed because “nowhere does plaintiff allege that Plavix would not be prescribed for any class of
patients.” Id. at *3 (emphasis added).
K. Section 6(d): Adopted in Larkin v. Pfizer, Inc., 153 S.W.3d 758 (Ky. 2005)
The plaintiff filed suit alleging negligence, breach of warranty, and strict liability against two drug
manufacturers for adverse reactions he experienced after taking the nonsteroidal anti-inflammatory drugs,
Zithromax and Daypro. The plaintiff based his suit upon the following: the Zithromax sample package provided to him by his physician contained no written instructions or warning information regarding risks or
potential side effects. In addition, at the time the plaintiff ’s prescription for Daypro was filled he contended
that no literature containing instructions or warnings associated with Daypro were present. After taking the
prescription medication the plaintiff developed toxic epidermal necrolysis as well as Stevens-Johnson syndrome.
The plaintiff ’s physician testified that although he was aware that the development of toxic epidermal
necrolysis and Stevens Johnson syndrome were known to occur from the ingestion of Zithromax and Daypro,
the physician did not believe these conditions to be common enough to discuss with the average patient.
The plaintiff premised his suit against manufacturers Pfizer, Inc. and G.D. Searle & Co. on the basis
that they had a duty to warn the ultimate consumer of the risks associated with the use of their respective
drugs. In adopting the learned intermediary doctrine under Restatement Third, the Supreme Court of Kentucky held that prescription drug manufacturer’s duty to warn of possible side effects is satisfied if adequate
warning is given to the patient’s health care provider.
The court reasoned that the learned intermediary doctrine is consistent with Kentucky’s informed
consent statute, which anticipates that doctors will inform their patients of any risks or dangers inherent in
their proposed treatment. See Ky. Rev. Stat. §304.40-320. The court further rejected the argument posited
by the plaintiff that adopting the learned intermediary rule would immunize manufacturers of prescription
drugs from products liability claims. Manufacturers continue to have a legal duty to warn; the rule identifies
only the party to whom warning should be given, that is, the health care provider who prescribes the drugs.
Thus, providing an adequate warning to the prescribing physician relieves the manufacturer of its duty to
warn the patient regardless of how or if the physician warns the patient.
III. Off-Label Use, the Dilemma
It’s Okay for the Doctor, But Not the Manufacturer?
A. Statistics Regarding the Use of Off-Label Prescription Drugs and Devices
1. Off-label uses of medical devices and drugs perform an important therapeutic role in many, if
not most, areas of medical practice. Thus, in some cases, if drugs were not used in an off-label
way, a physician could be guilty of malpractice. Fran Kritz, FDA Seeks to Add Drugs’ Uses to
Labels, Wash. Post, Mar 29, 1997 at 11 (quoting American Medical Association vice-president.).
In fact, the FDA recognizes off-label prescribing as a potentially useful practice. Linda A. Suydam, Senior Associate Commissioner, Keynote Address for FDLI Conference on Advertising and
Promotion in the New Millennium, Food and Drug Administration, Sept. 13, 1999.
a. Prescriptions for off-label uses of drug products may account for more than 25 percent of the
approximately 1.6 billion prescriptions written each year, with some estimates running as
high as 60 percent. Gregory Mundy, Current Medical Practice & the Food and Drug Administration, 229 JAMA 1744, 1746 (1974) (describing prevalence of off-label use in treating angia
and hypertension). The off-label use of beta-blockers following heart attacks has “proved of
immense value.” FDA Prioritized List of Off-Label Uses Deemed Most Important by 10 Professional Societies, 5 Health News Daily 4 (May 6, 1993) (quoting letter from FDA).
b. More than 80 percent of AIDS patients are treated with at least one off-label drug, and
more than 40 percent of all drugs prescribed for AIDS treatment are prescribed off-label.
Carol Brosgart, Off-Label Use in Human Immunodeficiency Virus Disease,12 J. Acquired
Immune Deficiency Syndromes & Human Retrovirology 56, 57-58 (1996).
c. Some 70 percent of kidney dialysis patients use their dialysis equipment in an off-label
manner. FDA and Dialyzer Makers Spar Over Device Reuse, Food & Drug Letter, Apr. 8,
1994.
d. Off-label use of bone screws occurs “in a large portion of the 30,000 to 70,000 spinal stabilization procedures performed annually.” Pedical Screws, 21 FDA Med. Bull. 10 (1994); see,
e.g., American Academy of Orthopedic Surgeons, Position Paper (Oct, 27, 1993) (“surgery
utilizing pedicle screws represents the best available treatment for patients”).
e. Most diseases afflicting fewer than 200,000 Americans are “totally without” FDA-labeled
treatment. Some 90 percent of patients must rely on off-label uses to have any treatment at
all. Abbey S. Myers, Pres. National Org. for Rare Disease, Inc., Prepared Testimony before
Subcomm. on Human Resources and General Discussion of other Off-label Uses; see Katie
Rodgers, Dealing with Incontinence, 140 Drug Topics 114 (1996) (six of seven treatments
for urinary tract incontinence in guidelines for Agency for Health Care Policy & Research
are off-label uses).
B. Off-Label Use Defined
1. The FDA regulates off-label use of prescription drugs through its authority over labeling and
advertisement.
a.Definitions
i. “Label” is defined as “a display of written, printed or graphic matter upon the immediate container of any article” 21 U.S.C. §321(k).
ii. “Labeling” encompasses all labels and other written, printed or graphic matter on any
container or wrapper or anything accompanying the drug. 21 U.S.C. §321(m).
2. The FDA’s authority to regulate off-label use of drugs is derived from the Federal Food, Drug and
Cosmetic Act.
a. The FDA, through the Federal Food, Drug and Cosmetic Act, 21 U.S.C. §§301-395, has the
authority to regulate the labeling of prescription drugs.
3. The FDA begins regulation of a prescription drug through a new drug application.
a. The regulation process begins with the new drug application (NDA). 21 U.S.C. §335(a); 21
C.F.R. §314 et seq.
b. The labeling, or package insert, submitted by a manufacturer must (1) “contain a summary
of the essential scientific information needed for the safe and effective use of the drug,” 21
C.F.R. §201.56(a)(1); (2) “be informative and accurate and neither promotional in tone nor
false or misleading in any particular,” 21 C.F.R. §201.56(a)(2); (3) “be based whenever possible on data derived form human experience,” C.F.R. §201.56(a)(3); and (4) not contain
any “implied claims ... if there is inadequate evidence of safety or a lack of substantial evidence of effectiveness.” Id.
c. Manufacturers must provide the FDA with “specimens of the labeling proposed to be used
for such drug.” 21 U.S.C. §335(b)(6).
d. The “intended uses” contained in a drug’s labeling must take into account the “objective
intent” of the manufacturer.
e. The “objective intent” of the manufacturer is determined by the express language of the
labeling and any other circumstances surrounding distribution of the drug including,
advertisement and oral or written statements that may indicate an intended use. 21 C.F.R.
§201.128.
f. “[I]f a manufacturer knows, or has knowledge of facts that would give him notice, that a
drug introduced into interstate commerce by him is to be used for conditions, purposes, or
uses other than the ones for which he offers it, he is required to provide adequate labeling
for such a drug which accords with such other uses to which the article is to be put.” Id.
4. The FDA must approve all proposed labels of a prescription drug. 21 U.S.C. §355(d); 21 C.F.R.
§2021.1(d)(2)(e).
a. The FDA’s policy on “approved” or “labeled” uses is embodied in 21 C.F.R. §201-57(c)(2):
“all indications shall be supported by substantial evidence of effectiveness based on adequate and well-controlled studies as defined in §314.126(b) of 21 C.F.R.”
b. The FDA will not approve a prescription drug if its label contains information that is false
or misleading in any particular. Any labeled drug that is false or misleading will be considered misbranded. 21 U.S.C. §352(a).
i. The FDA will also consider that a drug is misbranded if the labeling fails to provide adequate directions for use in a safe and intelligible manner or if it fails to
warn against use in certain pathological conditions or in unsafe amounts. 21 C.F.R.
§5201.5; 21 U.S.C. §5352(f).
5. Instances in which the FDA regulates off-label use of drugs by requiring a manufacturer to provide warnings.
a. A manufacturer must provide warnings for off-label uses when it has knowledge that
its drug will be not be used for its intended purpose. “[I]f a manufacturer knows, or has
knowledge of facts that would give him notice, that a drug introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the uses for which
he offers it, he is required to provide adequate labeling for such a drug which accords with
such other uses to which the article is to be put.” 21 C.F.R. §201.128.
b. FDA requires that the labeling “must describe clinically significant adverse reactions
(including any that are potentially fatal, are serious even if infrequent, or can be prevented
or mitigated through appropriate use of the drug), other potential safety hazards (including those that are expected for the pharmacological class or those resulting from drug/
drug interactions), limitations in use imposed by them (e.g., avoiding certain concomitant
therapy), and steps that should be taken if they occur (e.g., dosage modification). 21 C.F.R.
§201.57(c)(6)(i).
c. The FDA may require that package inserts refer to off-label uses. If there is a common
belief that the drug may be effective for a certain use or if there is a common use of the
drug for a condition, but the preponderance of evidence related to the use or condition
shows that the drug is ineffective, the Food and Drug Administration may require that the
labeling state that there is a lack of evidence that the drug is effective for that use or condition. 21 C.F.R. §201.57(c)(2)(ii).
d. The FDA may also require a specific warning in the warning section. A specific warning
relating to a use not provided for under the “Indications and Usage” section of the labeling
of a drug may be required by the FDA if the drug is commonly prescribed for a disease or
condition and such usage is associated with a clinically significant risk or hazard. 21 C.F.R.
§201.57(c)(6)(i) In addition, certain contraindications or serious warnings associated with
the drug, particularly those that may lead to death or serious injury, may be required to be
placed in a prominently displayed box on the label. 21 C.F.R. §201.57(c)(1).
C. Physician, Not Manufacturer, Liability For Prescribing a Drug and/or
Device For an Off-Label Use
1. Physician prescribes a drug and/or device and fails to get the patient’s informed consent.
a. A patient must be given all information that would be required in order for a reasonable
patient to make an informed decision. Matthies v. Matromonaco, 733 A.2d 456 (N.J. 1999);
see also Largey v. Rothman, 540 A.2d 504, 508-10 (N.J. 1988).
b. Significantly, one court has held that a manufacturer has no duty to warn of off-label use
that becomes standard medical practice as long as the manufacturer has not withheld
important information from the medical profession. Proctor v. Davis, 689 N.E.2d 23, 32-34
(III. App. Ct. 1997), reh’g den. (no duty to warn regarding off-label or non-indicated administration of corticosteroid via periocular injection when such use of product and side effect
of that use are well known in relevant medical community).
2. The physician fails to follow the labeling re: indicated use.
a.In Rule v. Best Industries, Inc., a catheter broke off during surgery, causing injury to the
patient. 121 F.3d 700 (4th Cir. 1997). A products liability suit was filed against the manufacturer alleging a failure to warn against the type of misuse engaged in by her doctors. The
trial court awarded summary judgment to the manufacturer. On appeal, the court affirmed.
It held that there was no evidence to support the patient’s theory that the manufacturer
had failed in its duty to warn against the misuse by the doctors or that the doctors’ actions
were a foreseeable and dangerous misuse of the product. Id. at 8. Even though there was no
warning against the particular misuse by patient’s doctors, there was a clear instruction of
proper use that, if followed, would have eliminated the possibility of such misuse. As such,
the court did not hold the manufacturer liable because it did provide warning.
D. Manufacturer Lability for Off-Label Use
1. FDA does not prohibit off-label use of medical devices.
a. It is well established that the FDA does not prohibit “off-label” use of medical devices. See,
e.g., Southard v. Temple Univ. Hosp., 781 A.2d 101, 104 (Pa. 2001). While the FDA controls
the marketing and labeling of medical devices, it does not attempt to interfere with the
practice of medicine. Id.; see also 21 U.S.C. §396 (“Nothing in this chapter shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or
administer any legally marketed device to a patient for any condition or disease within a
legitimate health care practitioner-patient relationship.”). Likewise, the FDCA “regulates
the manufacture and marketing of medical devices, not the practice of medicine.” WolickiGables v. Arrow Int’l, Inc., 641 F. Supp. 2d 1270, 1283 (M.D. Fla. 2009). The Supreme Court
has emphasized that off-label use “is an accepted and necessary corollary of the FDA’s mission to regulate in this area without directly interfering with the practice of medicine.”
Buckman Co. v. Plaintiffs’ Legal Comm., 531 U.S. 341, 350 (2001).
b. Courts have dismissed claims at summary judgment that were based on a manufacturer
allowing a physician to use a medical device in an “off-label” manner. See, e.g., Little v.
Depuy Motech, Inc., No. 96CV-0393, 2000 WL 1519962, at *9 (S.D. Cal. June 13, 2000) (the
physician’s “decision to use [the] device in an ‘off-label’ manner does not subject the manufacturer to liability, even if it knows of the off-label use. Accordingly, [the manufacturer]
cannot be held liable for [the physician’s] decision to implant the [] device in an off-label
manner.”); Cox v. Depuy Motech, Inc., No. 95-CV-3848, 2000 WL 1160486, at *8-*9 (S.D.
Cal. Mar. 29, 2000) (“A physician may use any device legally on the market in any way the
physician deems appropriate which may be consistent with the seller’s labeling or ‘offlabel,’ as in this case. A seller is not liable even if it knows of off-label use.”); Davenport v.
Medtronic, Inc., 302 F. Supp. 2d 419 (E.D. Pa. 2004).
c. Off-label use should not preclude the preemption of claims involving PMA devices under
Riegel. In fact, Riegel itself involved an off-label use. See Riegel v. Medtronic, Inc., 128 S.Ct.
999, 1005 (2009) (device employed in diseased and calcified artery, despite contraindication of such use, and device was inflated beyond rated burst pressure). Other courts have
applied Riegel preemption for off-label uses. Wolicki-Gables v. Arrow Int’l, Inc., 641 F. Supp.
2d 1270, 1284-88 (M.D. Fla. 2009). Differences exist, however. See supra, Federal Preemption.
d. A physician acts as a “learned intermediary” between the manufacturer and the patient,
and it is the physician, not the patient, who determines whether the drug or device is
appropriate for the patient. As a result of the physician’s role as the learned intermediary,
the manufacturer need not warn a patient directly of the risks of the product. Instead, the
manufacturer’s duty is fulfilled “when it has informed the prescribing or treating physicians of the risks of harm from the drug [or device] so that they may intelligently decide on
its use and advise the patient.” If it is proven that the manufacturer did not omit any such
dangers, it is the physician, not the manufacturer that will be held liable. Tauzier v. Dodge,
No. 97-2444, 1998 WL 227170 (E.D. La. May 5, 1998); Easterling v. Cardiac Pacemakers,
Inc., 1998 WL 50021 (E.D. La. Feb. 6, 1998).
2. Where physician aware of off-label use and risks.
a.In Huntman v. Danek Medical, Inc., the plaintiff had back surgery during which her doctor
used the defendant’s medical device. No. 97-2155-IEG RBB, 1998 WL 663362, at *4 (S.D.
Cal. July 24, 1998) (applying California law). The plaintiff had ongoing problems after the
surgery and subsequently learned that her doctor had used the defendant’s device in an offlabel manner. Id. The “learned intermediary” doctrine came into play as the court noted
that plaintiff ’s physician testified that he was aware of the risks involved in these procedures based on his independent research. Id. at *17. The plaintiff ’s physician further testified that he was generally aware of the lack of FDA approval for the pedicle fixation from
other doctors and that the defendant’s representative specifically informed the physician
that there was no FDA approval for the pedicle fixation. Id. The court dismissed the plaintiff ’s claims for failure to warn, fraud, and breach of warranty based on the “learned intermediary” doctrine. A critical inquiry for the court was whether the doctor was provided
with adequate warnings. The court noted also that the adequacy of the warnings is immaterial where the doctor knows of the specific risks. Id. at *18 (citing Rosburg v. Minn. Mining
& Mfg. Co., 226 Cal. Rptr. 299 (Ct. App. 1986)). In this case, the uncontroverted testimony
was that the physician had an independent knowledge of the risks and off-label nature of
pedicle fixation.
3. Manufacturer not liable for off-label use where warnings adequate.
a.In Broderick v. Sofamor Danek Group, Inc., the plaintiffs brought a products liability suit
against a manufacturer alleging strict liability in tort, negligence, fraudulent marketing and
promotion, and loss of consortium. 1999 WL 1062135 (S.D. Fla. Apr. 9, 1999). The defendant manufacturer’s orthopedic screws were implanted in plaintiff ’s back, a use not then
approved by the FDA. Id. The court held that, although misused, the manufacturer was not
liable. First, defendant manufacturer’s failure to disclose the FDA regulatory status of its
product could not constitute a material misrepresentation where the plaintiff ’s surgeon was
under no obligation to inform the plaintiff of the status. In addition, the court determined
that the defendant manufacturer sufficiently warned the plaintiff, through his surgeon, of
the product’s risks via the contents of its insert package. Id.
4. Liability where manufacturer has knowledge of off-label use but fails to provide adequate warning.
a.In Anderson v. Sandoz Pharmaceuticals Corp., the plaintiff contended that the defendant
failed to provide an adequate warning concerning the dangers of Parlodel. 77 F. Supp. 2d
804, 807 (S.D. Tex. 1999), abrogated on other grounds, Ackermann v. Wyeth Pharm., 526
F.3d 203 (5th Cir. 2008). Although the warnings included the “reaction” suffered by the
plaintiff, myocardial infarction, it was referenced only in the context of physiological lactation or uncontrolled hypertension. The warnings did not connect myocardial infarction
to plaintiff ’s particular diagnosis—reactive hyperprolactimia. Therefore, despite the fact
that the package insert alluded to a possible connection between Parlodel and myocardial infarction, it did not specifically warn that women who take Parlodel to treat reactive hyperprolactimia face the risk of myocardial infarction. Id. The defendant explained
that the reason the Parlodel package insert did not include information related to reactive
hyperprolactimia is because the defendant does not recommend that physicians use Parlodel to treat this condition. Even though the physician prescribed Parlodel for non-indicated use, the defendant was not released from liability because the court was presented
with evidence that the defendant had commissioned a research study regarding the dangers associated with the use of Parlodel, which apparently was not shared with the physician. Consequently, the defendant’s knowledge of the off-label use raised the issue that the
defendant had a duty to share its research, concerning the risks of off-label use, with the
physician. Id. at 808.
b.In Medics Pharmaceutical Corp. v. Newman, the plaintiff presented evidence that the defendant knew or should have known that physicians were regularly prescribing DES to prevent
miscarriages, an off-label use. 378 S.E.2d 487 (Ga. Ct. App. 1989). The court denied the
defendant’s motion for directed verdict stating that “[b]ecause a jury issue was presented
as to the foreseeability of the drug’s use to prevent miscarriages, a jury issue was also presented as to whether defendant used reasonable care in determining whether the drug was
safe for that use.” Id. at 488-89.
5. Liability for false advertising by a manufacturer
a. Lanham Act. Dissemination of off-label information by a pharmaceutical company may
lead to Lanham Act claims. The Lanham Act provides a cause of action for unfair competition by false advertising. See 15 U.S.C.A. §1125(a). There are five essential elements to a
Lanham Act false advertising claim: (1) false and misleading statements; (2) actual deception or tendency to deceive; (3) deception that is material in that it influences purchasing
decisions; (4) advertising goods in interstate commerce (for jurisdictional purposes); and
(5) likelihood of injury to the plaintiff (declining sales, loss of good will). See U.S. Healthcare, Inc. v. Blue Cross of Greater Philadelphia, 898 F.2d 914, 922 (3d Cir. 1990).
b. Violation of state consumer statutes. Many states have enacted consumer protection statutes. For instance, California’s Business and Professions Code section 17200 also prohibits
the making of false or misleading statements concerning a product. Similarly, the Illinois
Consumer Fraud & Deceptive Business Practices Act accomplishes the same protection
concerning labels and statements made in connection with a product. See Rubel v. Pfizer
Inc., 361 F.3d 1016 (7th Cir. 2004).
c. A manufacturer’s promotion of a drug or device for an unapproved use may form the basis
of an alleged violation of the Lanham Act or a state consumer statute. Violation of such
statutes would subject a manufacturer to additional damages.
E.Conclusion
1. As long as a manufacturer can establish that it gave adequate warnings to the physician about
adverse effects, contraindications, and dosages, most courts will not hold the manufacturer liable if the physician disregards the “indications” portion of the package insert or the PDR, and
prescribes the drug for non-indicated condition. However, the more prevalent a non-indicated
use becomes, the greater the likelihood that the off-label use will create liability, particularly
if the manufacturer fails to modify its labeling to warn about the risks of such non-indicated
usage.
2.Riegel preemption may still apply to PMA devices regardless of off-label use.
3. Furthermore, if dissemination of off-label information is false or misleading, it may lead to
potential liability under the Lanham Act and/or various state consumer statutes, such as, section
17200 of California’s Business & Professions Code.
Defending Failure-To-Warn Claims
Maja C. Eaton
Sidley Austin LLP
1 S. Dearborn Street
Chicago, IL 60603
(312) 853-7000
[email protected]
Maja C. Eaton is a partner in Sidley’s Chicago office and a global coordinator for
the Products Liability and Mass Torts practice. She has defended and tried a variety
of products liability cases, from toxic tort litigation to mass tort litigation involving
pharmaceuticals and medical devices. Maja’s background in the sciences lends itself
well to this practice area, and she has substantial experience in the development of
trial themes, expert witnesses and company defenses involving a variety of scientific
and medical disciplines. Maja’s leadership and relationships with her clients have
earned her recognition by Benchmark Litigation, LMG Life Sciences, Chambers USA
and Legal 500 as one of the country’s leading lawyers in the defense of product
liability and mass torts litigation. Maja would like to extend her thanks and deep
appreciation to her Sidley colleague Jennifer Foster for her valued assistance with
this presentation.
Table of Contents
I.Presentation..................................................................................................................................................55
Attachment 1...............................................................................................................................................................67
Attachment 2...............................................................................................................................................................73
Attachment 3...............................................................................................................................................................75
Defending Failure-To-Warn Claims ■ Eaton ■ 53
I.Presentation
• Failure-to-warn claims are probably the most common claims that are asserted in prescription
drug and medical device cases, and here’s why:
• Failure-to-warn claims often are “simpler” for plaintiff lawyers to prove than manufacturing defect or design defect cases
• It is often easier to prove that a “simple” warning could have been given, even when a
design could not feasibly have been improved.
• Design and manufacturing defect claims, particularly in device cases, typically
involve complicated engineering and technological issues – and in design defect
cases, plaintiffs typically must prove that an alternative design was both available, feasible and economical
• It may be easier for plaintiffs to find an expert to opine that a different warning could or
should have been given than to opine that a different design should have been used.
• Plaintiffs’ proof involves creating the impression of a “knowledge gap” between the drug or
device company and physicians and/or patients, which is easy for a lay jury to understand.
See, e.g., Hansen v. Baxter Healthcare Corp., 764 N.E.2d 35, 43 (Ill. 2002) (upholding $18
million jury verdict in favor of plaintiff, finding that the “jury’s general verdict for plaintiff
could have been reasonably based on a finding that Baxter’s knowledge with respect to the
use of friction-fit connectors was superior to that of the medical community and thus Baxter breached its duty to warn.”)
• Such “knowledge gap” arguments are aided by the appeal and psychology of 20/20 hindsight or arm-chair quarterbacking arguments. See, e.g., L. H. Brown, D. J. Cooper & C. G.
Campbell, Tackling Hindsight Bias in Failure-to-Warn Cases, For the Defense (Oct. 2010)
(“It is critical at the outset of a case, or as early as possible, to develop a defense story that
will take jurors back in time” to understand what the company knew before the plaintiff
sustained injury, rather than judging the case with the benefit of hindsight.).
• If jurors want to place blame because a plaintiff has serious injuries, they are more inclined
to blame a drug or device company than a treating physician
• Show and Tell: Drug Labeling vs. Device “Instructions For Use” – a brief explanation of the format and different sections within these informational sources.
• Overview: Drug labeling requirements are governed by 21 C.F.R. Part 201; medical device
labeling requirements are governed by 21 C.F.R. Part 801.
• Example: 2014 Actos® label
• Indications: Indicated uses become important when we talk about “off-label” uses and “offlabel promotion”
• NB: There is a difference between a company’s “off label promotion” of a drug or
device, and a doctor choosing to use a drug or device “off label” – one is legal (the
FDA does not regulate the practice of medicine), while the other is prohibited by
FDA. Failure to warn cases often lie in the crux. See, e.g., 21 C.F.R. §396 (clarifying
that the drug labeling regulations are not meant to regulate the practice of medicine);
see also FDA Guidance for Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference
Publications on Unapproved New Uses of Approved Drugs and Approved or
Cleared Medical Devices (Jan. 2009).
• Warnings and Precautions – FDA has now merged these sections, but older drugs may still
use the differentiated terminology. 21 C.F.R. §§201.56-201.57.
• Adverse events reported during clinical studies, as distinguished from adverse events
reported as part of the company’s post-marketing commitments. 21 C.F.R. §201.57.
•For devices, the label is called the “instructions for use” and must include information such
as implant technique, adverse events, and possible complications. 21 C.F.R §801.5.
• Example: Cardiac lead IFU
• The most important thing to remember about package inserts and instructions for use is that
their content is highly regulated by FDA. See 21 C.F.R. Parts 201 & 801.
• A prescription drug’s initial labeling is approved by FDA, and changes made thereafter
must be made by way of CBE-0s or NDA Supplements. See FDA Guidance for Industry:
Safety Labeling Changes—Implementation of Section 505(o)(4) of the FD&C Act
(July 2013).
• For PMA-approved Class III medical devices, IFUs are also approved as part of a Pre-Market Approval application, and changes thereafter are often by way of PMA Supplements. See
21 C.F.R. Part 814 (setting forth regulations that govern the PMA process).
• The process by which new information is added to a label is via post-marketing monitoring of
adverse events in the field and in clinical studies.
• For drugs, this is called pharmacovigilance. See 21 C.F.R. §314.80 (“Postmarketing Reporting of Adverse Drug Experiences”). Section 314.80 describes the different kinds of reports
a company must make to FDA of adverse events, depending on their severity. For example,
serious and unexpected adverse events must be reported within 15 days, whereas expected
and non-serious events may be reported less frequently. 21 C.F.R. §314.80(c).
• For medical devices, this process is called product reporting or testing or evaluation of
returns. See 21 C.F.R. Part 803 (“Medical Device Reporting”).
• Part 803 includes a lot of helpful information for device manufacturers facing the
issue of what to report and when to report it.
•For example, 21 C.F.R. §§803.1 & 803.10 explain the different entities who are subject to the device reporting requirements.
•Subsections 21 C.F.R. §§803.50-58 set forth the specific requirements that apply to
the reporting of adverse events by manufacturers, including foreign manufacturers.
• Similarly, 21 C.F.R. Part 820 sets forth the quality systems regulations that medical
device companies should follow to ensure that their devices constantly meet federal
requirements for sale and marketing. These requirements are known as “current good
manufacturing practices,” or “cGMPs” for short.
• New adverse event information can come to the company from a variety of sources, including adverse event reports, clinical trials, and medical literature, which should be monitored
and analyzed over time to evaluate changes in the frequency and/or type of adverse events.
• Drug and device companies have entire pharmacovigilance or device reporting staffs devoted
to the analysis of incoming reports, returned devices, and reporting to FDA. A favorite tactic of
plaintiffs’ counsel in failure-to-warn cases is to argue that these staffs are improperly trained or
inadequately resourced/staffed, which creates a “knowledge gap.”
• The “knowledge gap” that plaintiffs’ lawyers attempt to portray and exploit is the gap
between adverse events occurring in the field and which allegedly were or should have
been known to the company versus what the company told the FDA and the medical community.
• Thus, to properly defend a failure to warn claim, defense lawyers must determine what
was being reported to the company, how the company was evaluating it and reporting it to
FDA, and what was being communicated to physicians. In addition, defense lawyers must
understand what was available in the medical literature, including conferences, about the
particular adverse event at issue.
• This means understanding the company’s pharmacovigilance (or quality systems)
methodology, and its strengths and weaknesses.
• It also means understanding the company’s reporting relationship with the FDA
•What is the record of correspondence with FDA, if any, on the particular adverse
event at issue – were supplements submitted and rejected? Did FDA suggest a
labeling change? A Dear Doctor letter? Were adverse events appropriately captured
and reported in Annual Reports and/or PSURs?
•Was the company ever cited for late or unreported events, or other irregularities in
the handling of adverse events?
• It also requires an understanding of the different methods the companies used to
inform physicians about product-related issues – letters to physicians, technical bulletins, etc.
• In addition, defense attorneys must become conversant with FDA’s regulations governing prescription drug adverse events and medical device reporting, as well as
FDA’s Guidances and draft Guidances on Adverse Event Reporting for prescription
drugs and Medical Device Reporting. See FDA Guidance for Industry: Postmarketing Adverse Experience Reporting for Human Drug and Licensed Biological Products : Clarification of What to Report (1997) (drugs); FDA,
Mandatory Reporting Requirements: Manufacturers, Importers and
Device User Facilities (Jul. 15, 2014) (devices), available at http://www.fda.gov/
medicaldevices/deviceregulationandguidance/postmarketrequirements/reportingadverseevents/default.htm.
• How does this translate into an individual failure-to-warn case?
• Drugs and medical devices are inherently risky products and, when a person is injured, a
common response is to look for someone or something to blame. Drug and device companies are an easy target and usually have deep pockets, which is appealing to plaintiffs’ attorneys.
• Plaintiffs may use theories of negligence of strict product liability to assert a failureto-warn claim against a drug or device company. The choice largely depends on what
is allowed under state law, whether the claims merge before the jury, and the potential
defenses that defendants may raise to such claims under the governing state law. See, e.g.,
Woodill v. Parke Davis & Co., 79 Ill. 2d 26 (1980) (finding that a strict liability failure-towarn claim may lie where plaintiff alleges that the drug manufacturer knew, but failed to
warn about, an alleged problem with the drug, which caused the plaintiff ’s alleged injury);
Carlin v. Superior Court, 13 Cal. 4th 1104 (1996) (concluding that plaintiff may bring
failure-to-warn claim in either strict liability or negligence, the difference being that the
reasonableness of the manufacturer’s conduct has no relevance in a strict liability case);
Kansas Products Liability Act, K.S.A. §60-3302(c) (“all legal theories of recovery . . . are to
be merged into one legal theory called a ‘product liability claim’”).
• In most jurisdictions, the common elements of a failure-to-warn claim are that (1) the
company knew or should have known about a risk with its product about which it failed
to warn, (2) had the company provided a different warning, the product would not have
been prescribed or would have been used in a different way, and (3) because no warning,
or an inadequate warning, was given, the plaintiff sustained injury. See, e.g., Simon v. Wyeth
Pharms., Inc., 989 A.2d 356 (Pa. 2009) (acknowledging both proximate and actual causation as required elements of a failure-to-warn claim); Proctor v. Davis, 291 Ill. App. 3d 265
(1st Dist. 1997) (holding that drug manufacturers must keep abreast of emerging safety
information and warn about those risks that are known or knowable).
• These elements typically are not difficult to allege, especially at the pleadings stage of
litigation. As such, failure-to-warn claims are rarely dismissed before depositions are
taken, unless there is a reasonable argument for preemption (discussed below).
• Restatements (Second and Third) of Torts on Failure-to-Warn Claims
• Restatement (Second) of Torts §402A, comment k: “There are some products which, in the
present state of human knowledge, are quite incapable of being made safe for their intended
and ordinary use. These are especially common in the field of drugs. . . . Such a product, properly prepared, and accompanied by proper directions and warning, is not defective, nor is it
unreasonably dangerous. The same is true of many other drugs, vaccines, and the like, many
of which for this very reason cannot legally be sold except to physicians, or under the prescription of a physician. . . . The seller of such products, again with the qualification that they
are properly prepared and marketed, and proper warning is given, where the situation calls
for it, is not to be held to strict liability for unfortunate consequences attending their use,
merely because he has undertaken to supply the public with an apparently useful and desirable product, attended with a known but apparently reasonable risk.”
• This rule, which originated in 1965, continues to govern in a number of jurisdictions
in cases involving both medical devices and prescription drugs. See IADC, 50 State
Drug and Device Initial Check List (2013) (included with these materials). “Comment
k” provides the basis for the “learned intermediary rule” discussed below, and also
provides a “reasonableness” standard by which to judge the warnings a drug or device
company provided, even in strict liability cases.
• Restatement (Third) of Torts, §6: A warning defect exists when “reasonable instructions
regarding foreseeable risks of harm” are not provided to:
(1) prescribing and other health-care providers who are in a position to reduce the risks
of harm in accordance with the instructions or warnings; or
(2) the patient, when the manufacturer knows or has reason to know that health-care
providers will not be in a position to reduce the risks of harm in accordance with the
instructions or warnings.
• The Restatement (Third) of Torts is largely a codification of the common law “learned
intermediary doctrine,” which is the key rule you need to learn for purposes of defending
against failure-to-warn claims in the vast majority of jurisdictions
• The Learned Intermediary Doctrine
• The general rule in most states is that, with respect to prescription drugs and medical
devices, a manufacturer fulfills its duty to warn if it provides adequate warnings to the physician, not the patient. See, e.g., Carlin v. Superior Court, 13 Cal. 4th 1104 (1996); Kirk v.
Michael Reese Hosp. & Med. Ctr., 117 Ill. 2d 507, 519 (1987) (“The doctor, functioning as a
learned intermediary between the prescription drug manufacturer and the patient, decides
which available drug best fits the patient’s needs and chooses which facts from the various warnings should be conveyed to the patient, and the extent of disclosure is a matter
of medical judgment.”); Vacceriello v. Smith & Nephew Richards, Inc., 763 N.E.2d 160, 164
(Ohio 2002) (holding that “the physician has the duty to know the patient’s condition as
well as the qualities and characteristics of the drug [and] is in the best position . . . to balance the needs of patients against the risks and benefits of a particular drug or therapy, and
then supervise its use, shielding the manufacturer from liability under the learned intermediary doctrine”).
• Some states treat the learned intermediary doctrine as an affirmative defense, while others,
including Illinois, treat it as something a plaintiff must plead and prove (that the manufacturer failed to provide an adequate warning to the physician). Compare, e.g., Centocor, Inc.
v. Hamilton, 372 S.W.3d 140, 164 (Tex. 2012) (holding that, under Texas law, “the learned
intermediary doctrine is more akin to a common-law rule rather than an affirmative
defense”), with Vitanza v. Upjohn Co., 48 F. Supp. 2d 124, 131-32 (D. Conn. 1999) (treating
the learning intermediary doctrine as an affirmative defense under Connecticut law and
granting summary judgment to defendant drug manufacturer upon finding that adequate
warnings were provided to prescribing physician).
• Beware of certain outlier states that do not recognize the learned intermediary doctrine
and require warnings to go directly to the patient or end user. See Forst v. SmithKline Beecham Corp., 602 F. Supp. 2d 960 (E.D. Wis. 2009) (refusing to apply the learned intermediary doctrine in a Wisconsin case since no Wisconsin state court has ever adopted the
defense); State ex rel. Johnson & Johnson Corp. v. Karl, 220 W. Va. 463 (W. Va. 2007) (refusing to adopt the learned intermediary doctrine in West Virginia due to various policy
considerations); see also Rimbert v. Eli Lilly & Co., 577 F. Supp. 2d 1174 (D. N.M. 2008)
(concluding that New Mexico state courts would not apply the learned intermediary doctrine in the face of contrary state court authority suggesting the opposite).
• Many states also apply a heeding presumption to failure-to-warn claims – which can be a double-edged sword for drug and device manufacturers. The heeding presumption essentially creates a presumption that an adequate warning would have been read and heeded – and so can be
used helpfully in the defense of a warnings case where there is evidence suggesting that a physician did not read the package insert. However, it can also be used to aid the plaintiff ’s proof if
there is evidence that a warning was not adequate -Defending Failure-To-Warn Claims ■ Eaton ■ 59
• If your jurisdiction applies a heeding presumption, the court “presumes that warnings, if
given, will be heeded and followed and that medical practitioners will act competently.”
Mahr v. G.D Searle & Co., 72 Ill. App. 3d 540 (1st Dist. 1979) (applying Texas law); but
see Rutz v. Novartis Pharms. Corp., No. 12-cv-0026-MJR, 2012 WL 6569361 (S.D. Ill. Dec.
2012) (applying heeding presumption to determine that plaintiff met his burden of establishing proximate causation—that a different warning would have been read and heeded,
thus preventing his alleged injuries). If a court recognizes this presumption, and the warning is proved to be inadequate, it alleviates the plaintiff ’s burden of proving proximate causation. Still, it is a rebuttable presumption and the defendant drug or device manufacturer
may come forward with evidence that the presumption
• Not all courts recognize a heeding presumption. See, e.g., Rivera v. Phillip Morris, Inc.,
125 Nev. 18 (Nev. 2009); Moroney v. Gen. Motors Corp., 850 A.3d 629 (Pa. Super. 2004).
Moreover, the presumption is not uniform in those jurisdictions that do recognize it. For
example, in New Jersey, “once the party against which the presumption has been applied
produces sufficient evidence to rebut it, the presumption disappears.” In re Diet Drug Litig.,
384 N.J. Super. 525, 542 (N.J. 2005). Once the presumption disappears, the plaintiff once
again has the affirmative duty to present evidence in support of the argument that the physician, in fact, would have taken different steps had different warnings been given. Id. at
545 (“Should Wyeth produce evidence which rebuts the heeding presumption, the burden
of proof is on each plaintiff to establish that any failure to warn their health care professional of the risk of valvular disease was a proximate cause of their injury”).
• In light of the foregoing, the testimony of the prescribing (or implanting physician, for a
medical device) is typically crucial
• Clearly, the ideal situation occurs when a treating physician testifies that he/she found
the labeling to be adequate, and that it appropriately disclosed the information that
allowed him/her to make an informed prescribing decision. See Koenig v. Purdue
Pharma Co., 435 F. Supp. 2d 551, 555 (N.D. Tex. 2006) (granting summary judgment
to defendant drug manufacturer where prescribing physician testified that he was
aware of the risk about which plaintiff complained and that no additional information in the drug warning would have changed his treatment decision for the plaintiff);
Beale v. Biomet, Inc., 492 F. Supp. 2d 1360 (S.D. Fla. 2007) (same result and rationale
in medical device case involving partial knee prosthetic device)
• The doctor’s other sources of information are important here, too – many physicians rely on their training, the medical literature, their colleagues, and conferences
to learn about the risks and benefits of prescription drugs, or medical devices – and
will agree that based on these other sources of information, they were adequately
equipped to make an informed prescribing information. See, e.g., Centocor, Inc. v.
Hamilton, 372 S.W.3d 140, 170 (Tex. 2012) (“when the prescribing physician is aware
of the product’s risks and decides to use it anyway, any inadequacy in the product’s
warning, as a matter of law, is not the producing cause of the patient’s injuries.”);
cf. McNeil v. Wyeth, 462 F.3d 364, 373 (5th Cir. 2006) (“Where the physician would
have adequately informed a plaintiff of the risks of a disease, had the label been sufficient, but fails to do so on that account, and where the plaintiff would have rejected
the drug if informed, the inadequate labeling could be a ‘producing’ cause of the
injury, because it effectively sabotages the function of the intermediary.”); Porterfield
v. Ethicon, Inc., 183 F.3d 464 (5th Cir. 1999) (affirming summary judgment in favor of
defendant where prescribing physician testified that he never read the package insert,
but was independent aware of the risk about which plaintiff complained).
• Very few self-respecting physicians would agree (as plaintiffs’ lawyers will want them
to do) that they rely on drug or device sales reps for information important to their
practices.
• How can the learned intermediary doctrine affect causation defenses?
• Example: doctor testifies he/she never reads prescribing information – in this situation, the defendant may argue that no warning could have made any difference in
plaintiff ’s treatment, and plaintiff thus cannot prove that an inadequate warning was
the proximate cause of injury
• Example: doctor testifies that he/she was up-to-date on the medical literature and was
aware of the allegedly undisclosed risk, and prescribed the medication after weighing
the risks and benefits – the defendant then is able to argue that there was no information that would have made a difference to the prescribing decision, and hence, plaintiff has not proved proximate cause
• Example: doctor was unaware of the risk, but having been apprised of it since the prescribing decision, the new information would not have changed the decision to prescribe the drug or implant the device, based on the patient’s individual circumstances
– in this circumstance, as well, there is a failure of proof on the essential element of
proximate cause.
• Two key themes emerge from the points above:
• The learned intermediary doctrine is probably the most important aspect of defending failure to warn cases in drug and device cases and, with the right testimony, can
be a good way of getting your client dismissed on a motion for summary judgment.
• The testimony of the treating physician is often key to the strength or weakness of the
manufacturer’s defense
•It pays to find out as much as you can about the treating physician before you take
his/her deposition. Consider the following:
• Has he/she published in the relevant subject area?
• Is he/she a thought leader?
• H
as he/she accepted research grants or participated in speakers bureaus with
your client?
• W
hat can you learn from the company’s sales reps about the doctor and his/her
relationship to the company? Do the call notes reveal anything of concern? Are
there any company emails referencing the physician at issue aside from the call
notes database?
• W
ill he/she be represented by counsel at the deposition? Many states restrict the
type of contact defendants can have with treating physicians even in the context
of a lawsuit where the plaintiff has waived confidentiality of his/her medical condition. Check the rules of the state in which the claim is pending (you may need
to check the rules of the state in which the prescription was issued, as well). Also
be aware of any standing orders or case management orders that may govern the
individual case. If the physician is represented by counsel, you may be able to
have a number of the questions above answered by counsel before the deposition.
• I f the physician has also been sued, consider the benefits of suggesting a coordinated defense, rather than having defendants point fingers at each other.
Whether this approach is appropriate often depends on the nature and substance
of the claim against the medical defendant(s).
• Approaching the prescribing physician’s deposition
• Establishing treating physician’s knowledge base and sources of information
• D
epending on what you know about the physician and how the testimony is
going, you may or may not want to highlight or seek to discredit the doctor’s
qualifications
• E
stablishing that the risk-benefit decision is unique for every patient, especially
since all medicines and devices have risks
• G
etting the physician to acknowledge that there are no medicines or medical
devices that have no risks
• E
stablishing whether the physician read the manufacturer’s prescribing information or instructions for use - Did he/she review the prescribing information?
When was last time before prescription in question?
• E
stablishing the kinds of risks the physician usually discloses to patients using
the drug or device in question
• W
as the risk here so rare, and the need so great that the physician (a) would have
prescribed the drug anyway, and/or (b) would not have discussed the risk with
the patient?
• N
B: Many physicians say that they would never tell a patient all possible side
effects or else no patient would ever take medicine or agree to a needed medical procedure. Depending on the tone of the deposition, consider asking
questions of this nature during the proceeding.
• E
xploring causation – temporal associations between taking drug and adverse
event do not establish causation. This type of questioning requires familiarity
with the literature and science between the medicine/device and the injury at
issue.
• Possible exceptions to the Learned Intermediary Rule
•Oral contraceptives and some other limited kinds of drugs, like vaccines (minority rule). See, e.g., MacDonald v. Ortho Pharm. Corp., 394 Mass. 131, 135-36 (1985)
(finding that manufacturer of oral contraceptive owes duty directly to end users of
those contraceptives); Hill v. Searle Labs., 884 F.2d 1064, 1070-71 (8th Cir. 1989)
(same, contraceptive devices); Mazur v. Merck & Co., 964 F.2d 1348 (3d Cir. 1992)
(holding that “because it was foreseeable that the MMR II vaccine would be dispensed without an individualized medical judgment of the risks and benefits of
inoculation, Merck was obligated to warn users of the risks of its MMR II vac62 ■ Defending Drug and Medical Device Litigation: A Primer for Young Lawyers ■ September 2014
cine directly under the mass immunization exception to the learned intermediary
rule.”)
•A minority of courts also have carved out an exception to the learned intermediary
doctrine where the manufacturer has engaged in direct-to-consumer advertising.
See Perez v. Wyeth Labs., Inc., 161 N.J. 1, 21 (1999)
•Attorneys must also be cognizant of other kinds of voluntary manufacturer-sponsored programs and their potential impact on the Learned Intermediary Rule. Such
programs include patient classes for some kinds of self-administered drugs, e.g.,
interferons for hepatitis C; the involvement of non-medical company employees
in device monitoring or in the surgical suite itself (e.g., technical reps involved in
monitoring medical devices; sales reps in the OR). See, e.g., Hernandez v. Schering
Corp., 958 N.E. 447 (Ill. App. 1st Dist. 2011) (declining to find a “voluntary undertaking” exception to the learned intermediary doctrine in the face of evidence that
the manufacturer had sponsored a class for patients that included instructions
on use of a self-administered hepatitis C medication); Zappola v. Leibinger, Nos.
86038, 8602, 2006 WL 1174448, at *13 (Ohio Ct. App. May 4, 2006) (holding that
a manufacturer did not discharge its duty by putting a sales representative in the
operating room who did nothing more than provide written instructions for use
when the doctor had questions during the course of the operation).
• Other Methods Used by Manufacturers to Warn Physicians:
• Dear Doctor Letters: these often prompt lawsuits, especially if encouraged by FDA, and
themselves may be attacked as inadequate (e.g., Omniscan), especially if seen as promotional
• Plaintiffs’ lawyers also like to second-guess when a Dear Doctor Letter should have
been issued (e.g., Actos litigation claims)
• Typically, plaintiffs’ lawyers try to relate the lack of appropriate communication
through Dear Doctor Letters or other methods to inadequacies in the companies’
pharmacovigilance of device monitoring department or to a desire to put profits over
safety by “hiding” information that would reduce sales.
• Technical Insights: often used by medical device manufacturers to provide information on
technique to surgeons, designed to avoid complications
• Special Considerations in Failure-to-Warn Cases: Federal Preemption
• Preemption in device cases – failure-to-warn claims that are brought against device manufacturers typically are found to be preempted in their entirety by the Medical Device
Amendments to the Food, Drug & Cosmetic Act, 21 U.S.C. 360k. This section of the FDCA
contains an express preemption provision barring states from imposing requirements on
pre-market-approved Class III medical devices where those state requirements are different
from or in addition to those imposed by the FDCA and the FDA’s regulations promulgated
under it. See Riegel v. Medtronic, Inc., 552 U.S. 312 (2008).
• One key exception to this general rule of express preemption is for cases brought in
the courts of the Ninth Circuit, where the courts have allowed such cases to proceed
as non-preempted beyond the pleading stage. See Stengel v. Medtronic, Inc., 704 F.3d
1224 (9th Cir. 2013) (en banc) (holding that state law negligent failure-to-warn claims
were not preempted where those claims paralleled federal law requirements of the
MDA); Coleman v. Medtronic, Inc., 223 Cal. App. 4th 413 (2d Dist. 2014) (review subsequently granted) (applying Stengel to find state law failure-to-warn claims not preempted to the extent that they paralleled federal law requirements).
• Even with the narrow exception that the Ninth Circuit has allowed, it will typically
be quite difficult for plaintiffs to proceed with these types of failure-to-warn claims
against device manufacturers as it will be difficult to prove essential elements like
causation and proximate causation (i.e., that a failure to report adverse event reports
actually made any difference in the implanting physicians’ decision to use the device).
• On the other hand, and in stark contrast to cases involving premarket-approved Class III
medical devices, failure-to-warn claims are NOT preempted in the majority of prescription drug cases where such claims are raised. See, e.g., Wyeth v. Levine, 555 U.S. 555 (2009)
(holding that state law failure-to warn claims against antihistamine manufacturer were not
preempted by federal law, either on the theory that it was impossible for the drug manufacturer to modify the labeling once the FDA had approved it or on a conflict preemption theory that the state law imposed more stringent standards of compliance than their federal
law counterparts). The FDCA contains no similar express preemption provision applicable
to prescription drugs, and manufacturers’ attempts to apply implied preemption principles
have generally failed to limit failure-to-warn claims against drugs.
• Where preemption has or will be found is in cases involving prescription drugs where
the record is so clear that the precise warning plaintiffs claim should have been given
was presented to FDA in a labeling supplement or CBE-0 and the FDA rejected it. See,
e.g., Dobbs v. Wyeth Pharms., 797 F. Supp. 2d 1264 (W.D. Okla. 2011) (finding plaintiff ’s failure-to-warn claims preempted where Wyeth presented evidence that the FDA
would have rejected the enhanced warning plaintiff advocated); In re Fosamax Prods.
Liab. Litig., 951 F. Supp. 2d 695 (D. N.J.) (“Because the record contains clear evidence
that the FDA would not have approved a stronger warning to the Precautions section
of the Fosamax label, this Court grants the Motions on federal preemption”).
• Accordingly, where the record of correspondence with FDA makes it pretty clear that
a CBE-0 or labeling supplement would be futile, a preemption attack is also pretty
attractive
• Generic medications present their own host of preemption-related issues. See PLIVA, Inc.
v. Mensing, 131 S. Ct. 2567 (2011) (finding that, where it was impossible for a generic drug
manufacturer to change a drug label in accordance with federal regulations, state law failure-to-warn claims that would have required such action on the part of the manufacturer
were clearly preempted); see also Mutual Pharm. Co. v. Bartlett, 133 S. Ct. 2466 (2013)
(finding similar design defect claim preempted on same theory that generic drug manufacturer is expressly prohibited from making unilateral changes to drug labeling); Eckhardt v.
Qualitest Pharms. Inc., 858 F. Supp. 2d 792 (S.D. Tex. 2012) (same).
• There are, of course, exceptions, depending on how the failure-to-warn claims are
pled and presented. See, e.g., Huck v. Wyeth, Inc., 850 N.W.2d 353 (Iowa 2014) (finding that state law failure-to-warn claims against generic drug manufacturer were not
preempted to the extent they were based on the manufacturer’s failure to include
additional warning language that had been approved by the FDA after the plaintiff
began taking the drug); Phelps v. Wyeth, Inc., 938 F. Supp. 2d 1055 (D. Ore. 2013)
(holding that state law failure-to-warn claim based on generic manufacturer’s failure
to update warnings to match those of equivalent brand name medication were not
preempted).
• Another Special Consideration in Failure-to Warn Cases: Off-Label Promotion
• Off-label promotion occurs when a company promotes or advocates the use of a medicine
or medical device for something other than its indicated uses as approved by the FDA.
Such promotion, if proven, can lead to governmental investigations, qui tam actions, and
potentially draconian damages and fines, settlements, or even criminal penalties.
• Off-label promotion must be differentiated from off-label use of a drug or medical device
– something that FDA does not and cannot prohibit. See Southard v. Temple Univ. Hosp.,
566 Pa. 335 (2001); 21 U.S.C. §396. Indeed, the U.S. Supreme Court has emphasized that
off-label use is “an accepted and necessary corollary of the FDA’s mission to regulate in this
area without directly interfering with the practice of medicine.” Buckman Co. v. Plaintiffs’
Legal Comm., 531 U.S. 341, 350 (2001).
• Accordingly, courts have dismissed claims based on a manufacturer allowing a physician
to use a drug or medical device in an “off-label” manner.” See Little v. DePuy Motech, Inc.,
No. 96-0393, 2000 WL 1519962, at 9 (S.D. Cal. June 13, 2000) (physician’s decision to use
a device in an ‘off-label’ manner does not subject the manufacturer to liability, even if it
knows of the off-label use.); Cox v. DePuy Motech, Inc., No. 95-3848, 2000 WL 1160486, at
8-9 (S.D.Cal. Mar.29, 2000) (“A physician may use any device legally on the market in any
way the physician deems appropriate which may be consistent with the seller’s labeling or
‘off-label,’ as in this case. A seller is not liable even if it knows of the off-label use.”).
• The issue of failure to warn in off-label situations is very common. There is a great deal
of case law on the issue and the holdings are not always consistent since liability generally hinges on the manufacturer’s knowledge of the off-label use and of the risks associated
with such use. Generally, as the level of off-label use increases, courts tend to hold manufacturers to a higher level of responsibility for warning of dangers associated with known
off-label use. Where a duty to warn about off-label use is found, the adequacy of the warnings typically is evaluated using the same learned intermediary analysis, probing the doctor’s knowledge of the alleged risks. See, e.g., Huntman v. Danek Med., Inc., No. 97-2155,
1998 WL 663362 (S.D. Cal. July 24, 1998) (finding that implanting physician’s independent knowledge of the risks inherent in off-label use of pedical fixation device, known by
the physician to be off-label, obviated any inquiry into the adequacy of the manufacturer’s
warnings); Medics Pharm. Corp. v. Newman, 378 S.E.2d 487 (Ga. Ct. App. 1989) (“Because a
jury issue was presented as to the foreseeability of the drug’s [off-label] use to prevent miscarriages, a jury issue was also presented as to whether defendant used reasonable care in
determining whether the drug was safe for that use,” including whether the warnings were
adequate).
• Although most courts will not hold a manufacturer liable if the physician disregards the
“indications” portion of the package insert or a medical device’s instructions for use, the
more prevalent a non-indicated use becomes, the greater the likelihood that the off-label
use will create liability, particularly if the manufacturer fails to modify its labeling to warn
about the risks of the known non-indicated usage.
• With respect to medical devices, keep in mind that failure-to-warn claims based on alleged
off-label promotion may be preempted, and thus this defense must always be a primary
consideration in cases involving Class III pre-market-approved devices. In Coleman v.
Medtronic, Inc., for example, the court found that the plaintiff ’s state law failure-to-warn
claim was expressly preempted by the MDA to the extent it was based on the theory that
the manufacturer promoted off-label uses for the device, since any duty to warn about the
risks of off-label uses would be different from and in addition to federal requirements. 223
Cal. App. 3d 413 (Cal. 2d Dist. 2014) (review subsequently granted); Ramirez v. Medtronic,
Inc., 961 F. Supp. 2d 977 (D. Ariz. 2013) (same).
• Off-label promotion also raises First Amendment issues, which may be a back-pocket
defense in appropriate jurisdictions. See S.M. Greene & L. Noah, Off-Label Drug Promotion
and the First Amendment, 162 U. Pa. L. Rev. Online 239 (2014), available at www.pennlawreview.com/debates/index.php?id=50.
Attachment 1
DRUG AND MEDICAL DEVICE
Sacking the Monday
Morning Quarterback
By Loren H. Brown,
Tackling Hindsight
Bias in Failureto-Warn Cases
Daniel J. Cooper
and Christopher G. Campbell
Examining this
psychological tendency
and offering practical tips
to mitigate its effects.
In his 2003 New Yorker article “Connecting the Dots,”
Malcolm Gladwell resurrected the term “creeping determinism” to describe hindsight bias. Creeping determinism, he wrote, is “the sense that grows on us, in retrospect,
that what has happened was actually inevitable.” Malcolm Gladwell, New Yorker, Mar.
10, 2003. Psychologist Baruch Fischhoff
originally coined the term. Gladwell tells of
Fischhoff’s 1960s experiment in which, on
the eve of President Nixon’s visit to China,
Fischhoff asked a group of people about the
probability of the trip’s success. After Nixon’s trip received accolades as a diplomatic
victory, Fischhoff went back to those same
people and asked them to recall their own
predictions. Fischhoff reported that, overwhelmingly, the subjects “remembered”
being more optimistic than they had actually been. Those who had predicted a low
likelihood that Nixon would meet with
Mao, for instance, recalled after knowing that the meeting had occurred that
Loren H. Brown is co-chair of DLA Piper’s product liability practice and a partner
in the firm’s New York City office, where he
specializes in pharmaceutical and mass tort
litigation. Daniel J. Cooper is president of LitStrat Inc., a jury research
and litigation consulting firm based
in New York City. Christopher G.
Campbell is a partner in DLA Piper’s
Atlanta office, where he specializes in
product liability litigation.
n © 2010 DRI. All rights reserved.
they had predicted its likelihood as high.
After gathering the results of this experiment, Fischhoff wrote, “The occurrence of
an event increases its reconstructed probability and makes it less surprising than it
would have been had the original probability been remembered.” Id.
Others have recognized this phenomenon in jurors. In his book Legal Blame: How
Jurors Think and Talk About Accidents,
Neal Feigenson observed that in jurors, as
well as in the population generally, “hindsight bias is one of the most consistently
replicated effects in the cognitive psychology literature and has proven fairly resistant to attempts to reduce its impact.” Neal
Feigenson, Legal Blame 62 (APA 2001).
We face the challenge of eliminating or
at least mitigating hindsight bias in jurors
as defense lawyers in failure-to-warn cases.
Whether you call it creeping determinism,
Monday morning quarterbacking, or simply hindsight bias, as we will here, this psychological tendency presents a significant
obstacle in failure-to-warn cases. This is
particularly true in pharmaceutical product liability cases. Jurors have been known
to hold manufacturers to standards of near
omniscience when drugs or devices have
been accused of causing or contributing to
horrific injuries or deaths.
For The Defense
n
October 2010
n
15
This article has two purposes. The first
is to examine hindsight bias in pharmaceutical failure-to-warn cases and other legal
contexts. The second is to offer practical
tips to mitigate the effects of hindsight bias.
Hindsight Bias in Failureto-Warn Cases
Failure-to-warn cases invite hindsight bias.
It is critical at the outset
of a case, or as early as
possible, to develop a
defense story that will
take jurors back in time.
To establish a failure-to-warn claim in a
pharmaceutical product liability case, a
plaintiff must prove that the defendant
“knew or should have known” that the
drug in question was dangerous but failed
to adequately warn either the medical community or the public. See, e.g., Anderson v.
Owens-Corning, 810 P.2d 549 1002–1003
(Cal. 1991); Wolfgruber v. Upjohn Co., 423
N.Y.S.2d 95, 97 (N.Y. App. Div. 1979). This
“knew or should have known” standard
opens the door to hindsight bias, both
when jurors consider liability and when
plaintiffs bring up after-the-fact-of-injury
remedial measures to establish liability.
Of the two aspects of the standard, the
“knew” aspect or the “should have known”
aspect, it is “should have known” that
mostly leads to hindsight bias. Under the
“knew” aspect of the standard, the question is what the company actually knew at
the time of a plaintiff’s injury. This raises
an objective question. The issue turns on
actual facts—such as laboratory data or
clinical trial results—that show what the
company’s state of knowledge was during
the time in question.
In contrast, the “should have known”
part of the standard is subjective. As a result, there is great opportunity for hindsight
bias to creep in and affect the interpretation
of the facts. Under the “should have known”
standard, the question is not what a com-
16
n
For The Defense
n
pany knew, but what it might have known if
it had simply done more. In some cases, this
provokes a moral judgment. With the introduction of morality, the question shifts from
whether a company should have known of
the risk to whether the company is “good”
or “bad.” Jurors perceive that a “good company” would have done more studies before
putting a drug on the market, and a “bad
company” would not. Because many jurors
already have a negative view of the pharmaceutical industry, they may surrender
to hindsight bias and, on the basis of current knowledge, find that a defendant is a
bad company that should have done more
to protect patients.
Of course, regardless of the standard,
the facts of almost any failure-to-warn case
can invite hindsight bias. Take this classic
scenario: (1) a plaintiff is injured while taking a medication; (2) after the injury, data
emerges showing that the medication may
cause the injury at issue; and (3) the FDA
approves a revised label—which was not in
effect when the plaintiff took the medication—warning new patients that the injury
in question is a possible side effect.
Under these circumstances, it is not difficult to understand how hindsight bias
can play a role in a juror’s decision-making
process. Jurors exist in the present in their
own here and now. At the time when they
are asked to apply the “knew or should
have known standard,” they are not asked
to weigh the issues in the abstract but in
the face of a living, breathing plaintiff
who claims to have been injured by a defendant’s drug. When confronted with an
actual plaintiff and an actual injury, it is
difficult for jurors to put a plaintiff’s story
aside, travel back in time mentally, and explore what a manufacturer actually knew
or should have known at that time. On top
of this, most jurors view their role as unraveling the mystery of what happened to
a plaintiff, why it happened, and deciding
whom to blame. For those jurors looking for
someone to blame, hindsight bias makes it
easier for them to hold a defendant responsible and to find favorably for the plaintiff.
Moreover, and apart from the desire to
find someone or something to attribute a
serious injury to, most of us have a difficult time discarding some of the information that we have when we want to make a
“correct” judgment. As Fiegenson noted,
“jurors are inclined to take into account
whatever evidence they think will help
them reach a substantively correct result.”
Feigenson, at 105. As a result, jurors tend
to resist “debiasing” efforts. Even when
legal instructions direct jurors to assess
the reasonableness of conduct from the
time before or at the time of harm, jurors
are more likely to take the ex post perspective because this allows them to use
all the information that they have at hand.
According to Fiegenson, the psychological research teaches that jurors are more
likely to think, “If I know the outcome of
the parties’ conduct, why make believe that
I don’t? The outcome is what really happened, and taking it into account will help
me to reach a just decision about responsibility for what happened.” Id.
The issue of hindsight bias is further
complicated by the doctrine of subsequent
remedial measures, which can compound
hindsight bias. A common example of a
subsequent remedial measure in failure-towarn pharmaceutical cases is the existence
of a revised label after the fact that warns of
the very injury alleged by a plaintiff. While
the law does not expressly permit a plaintiff to present this evidence during a trial,
the plaintiff likely will have many opportunities to present evidence of a defendant’s
changes that were made to the warning
after a plaintiff suffered an injury.
The law provides an example of the broad
opportunity that plaintiffs can have to present evidence of subsequent remedial measures. See, e.g., Kimberly Eberwine, Note,
Hindsight Bias and the Subsequent Remedial Measures Rule: Fixing the Feasibility
Exception, 55 Case W. Res. L. Rev. 633,
652–55 (2005). Although prohibited generally, plaintiffs may introduce evidence of
subsequent remedial measures if the plaintiff seeks to prove the feasibility of a measure that the defendant could have taken
prior to the plaintiff’s injury or when the
defendant claims that “all reasonable care
was being exercised at the time.” Id. at 653
(citing Kenny v. Southeastern Penn. Transp.
Auth., 581 F. 2d 351, 356 (3d Cir. 1978)).
Evidence introduced under this exception can present challenges in a failureto-warn case, as the plaintiff might use
this exception to illustrate the relative ease
by which the company could have better,
or more adequately, warned the plaintiff
October 2010
about the potential harm that the plaintiff
suffered. After the fact the addition to the
label seems so simple to accomplish and
is typically reinforced by the prescriber
and the patient testifying that the change
would have mattered to them in their riskbenefit analysis. Even if not taken quite so
far, the plaintiff, at a minimum, readily
suggests that the absence of the remedial
language led the patient to believe that the
prior warning did not apply to him or her.
“Why not say more sooner? Why not do
more if it might protect even one patient
from the harm suffered by this plaintiff?
That’s what a company that places health
over profits would do, isn’t it? Why not
here?” are often questions posed by a plaintiff’s counsel for jurors hoping to lead jurors to conclude that it was the absence of
will and good intentions, not the absence
of knowledge, that motivated the labeling
choices of a company.
With evidence of fairly simple remedial
steps, juries may be more inclined to ignore
other evidence on the extensive research
and testing results that led a company to
conclude a product exhibited no evidence
of a risk, because they know that the injury
occurred, and the company later warned of
the potential for this injury. See, e.g., Eberwine, at 655–58 (discussing the magnifying effect of subsequent remedial measures
evidence on hindsight bias in juries). There
is often no good reply to the question, why
wasn’t more done sooner, why didn’t the
company discover the risk before it was
too late for this plaintiff? Thus, evidence of
subsequent remedial measures directly increases the impact of hindsight bias in juries because it supports the assumption that
the defendant should have known of and
warned about the injury from the outset.
Hindsight Bias in Other Areas
The effects of hindsight bias are not limited to failure-to-warn cases, and it is worth
taking a moment to discuss some of those
other areas. See, e.g., Donald S. Davidson
and Marie K.N. DeBonis, Overcoming the
Effects of Hindsight Bias, N.Y. L.J. S4, Col.
1, Oct. 14, 2003; see Kimberly Eberwine,
Note, Hindsight Bias and the Subsequent
Remedial Measures Rule: Fixing the Feasibility Exception, 55 Case W. Res. L. Rev.
633, 636–37 (2005). Two areas that present
valuable examples of the effects of hind-
sight bias can be found in patent and negligence law.
In patent cases, hindsight can affect the
issue of obviousness. A lack of obviousness
is one of the key requirements of patentability—that the technology in question
was new and not obvious at the time of
the invention. It is not difficult to imagine, however, that once a new invention
exists, stepping back in time and assessing whether it was obvious invites hindsight bias. For instance, in KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 399 (2007), the
U.S. Supreme Court ruled that an inventor’s modification of an existing gas pedal
design was an obvious change and, therefore, not deserving of patent protection. It
is easy to imagine how, when similar issues
come before a jury, hindsight bias might
affect the outcome. Once the matter comes
before a jury, the technology actually does
exist, and the jury is made of aware of
the process by which the technology was
invented, thereby potentially leading many
jurors to view the invention as more obvious than it was at the time of its development. Gregory N. Mandel, Does Hindsight
Bias Affect Obviousness Rulings?, Nat’l L.J.
S2, Col. 1, Aug. 18, 2008.
Courts and counsel dealing with these
issues in patent cases have suggested ways
to mitigate hindsight bias in that context.
For example, in KSR v. Teleflex, the U.S. Supreme Court discussed a “teaching, suggestion or motivation” approach in which
the patent is only proved obvious if prior
information reveals some motivation or
suggestion that would have generated the
technology in question. Patent law experts
have also suggested presenting a case that
focuses on the problem that the invention
solved. Mandel, Nat’l L.J. S2, Col. 1, Aug.
18, 2008.
At the core, jurors are often most interested in the inventor and the invention
story. While obviousness is the subject of
expert analysis on the issue of what a person of ordinary skill in the art would have
known at the time, the human interest element is what often grabs the attention of
the jurors—going back in time with the
inventor into the lab or to the research
bench, confronting a real problem, working hard, failing, and then finally arriving
at a valuable solution. By framing a case
in this way, the experts suggest that ju-
rors are put in a position that is more analogous to that of the inventor at the time of
the invention, when there was only a problem to solve and no known solution. Id. As
discussed below, a narrative that places the
jurors in the shoes of the decision makers at
the time of decision making is an approach
that can be useful in failure-to-warn cases.
In negligence and medical malpractice
cases, hindsight bias can actually favor
either a defendant or the plaintiff, depending on the facts of the case. Take a typical slip-and-fall case. If the question is one
of notice—whether the defendant knew
or should have known about a particular
hazard that caused the plaintiff to fall—
then hindsight bias may favor the plaintiff.
Jurors may view the fact that the plaintiff
fell as an event that the defendant should
have foreseen. In contrast, if the question is
whether the hazard was so open and obvious that the plaintiff him- or herself should
have seen it, then hindsight bias may actually favor the defendant. See Terrence W.
Campbell, Commentary: Open & Obvious:
Considerations of ‘Hindsight Bias,’ Mich.
Law. Wkly., 2005 WLNR 24503096, Feb.
14, 2005. In other words, the fact that the
plaintiff fell may lead jurors to overestimate
how open and obvious the hazard truly was
at the time of the injury, when in fact with
only foresight, the same conclusion would
not have been drawn. Id.
Tips for Tackling Hindsight Bias
You can attack hindsight bias in five particular ways: (1) develop a story through
your defense that transports jurors back in
time; (2) use discovery to develop facts to
fight hindsight bias; (3) use jury selection
to identify jurors susceptible to hindsight
bias; (4) during a trial, attack hindsight
bias head-on; and (5) carefully craft jury
instructions.
Develop a Story That Transports
Jurors Back in Time
Jurors respond to stories. The best trial
lawyers live by this creed. For example,
author Jim Perdue in Winning with Stories
explains, “So, why a story? Because stories
persuade at the subliminal level by using
the concept of vividness. They involve the
audience. The story uses the schema format
for storing and organizing information.
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ing the presentation easier and enlivens
by making facts fun.” Jim M. Perdue, Winning with Stories 20 (Tex. Bar 2006). Importantly, stories are easier to remember and
repeat and, as such, become an extremely
useable tool for jurors in deliberations. One
invaluable lesson for defense counsel is,
replace stacking facts and arguments with
a compelling, integrated narrative.
Experts can emphasize
that scientific knowledge is
constantly advancing and
that it is unfair to judge
yesterday’s decisions based
on today’s knowledge.
It is critical at the outset of a case, or as
early as possible, to develop a defense story
that will take jurors back in time to the relevant events or decisions and put those
events and decisions in context. For example, if a plaintiff claims that a company
should have known about a harmful side
effect, then the defendant needs a narrative that will transport jurors back to the
drug development phase and allow jurors
to see that process through the eyes of the
scientists involved at the time. In viewing
the process from a company’s perspective
and in the appropriate historical context,
jurors will be less likely to fall prey to hindsight bias. In addition, it is important to tell
a story about a plaintiff’s conduct before,
during, and after the plaintiff and a company “collided.” A plaintiff will tell one
story on the stand, but actions speak louder
than testimony, so you must focus jurors on
the plaintiff’s actual conduct at the relevant
times. Without attacking or explicitly criticizing a plaintiff, and adopting more of an
historian’s demeanor than an advocate’s,
you need to develop and control the character and decision-making discernment of
a plaintiff. To do that, you need to examine
in great detail a plaintiff’s history.
This storytelling process should start
before discovery. When reviewing com-
pany documents before discovery, for
instance, find those documents that can
provide the necessary historical context
that show a company’s state of knowledge
at a given time period. The regulatory
record documentation, particularly the
record documenting a medication’s label,
is a good example. It is important to show
jurors how the FDA’s rulings, negotiations,
and directions significantly influenced a
company’s decisions and played a key role
in a label’s final content. Ultimately, the
FDA is the final arbitrator of a label’s content and a product’s status in the market.
The same principle applies to company
witnesses. When talking to witnesses, make
a point of distinguishing between what the
witnesses know now as opposed to what
they knew at the relevant time. Hindsight
bias does not only affect jurors. There is a
very real possibility that company scientists and safety officers may “remember” in
hindsight things that may be detrimental to
your case. For example, if a new side effect
is revealed after a drug is put on the market, a company scientist, especially if he or
she wants to make a name for him- or herself, may claim in e-mails to peers that he
or she predicted the side effect years before
the drug was approved, but that his or her
predictions were ignored. You need to take
those statements seriously, and determining whether they are simply the product of
hindsight bias is critical. Focus on developing the facts needed to open a window into
the decision-making process that took place
in the laboratory or the boardroom at the
time in question. This means spending time
with witnesses to develop the pieces of the
puzzle required to humanize the story and
make it appealing to jurors.
Use Discovery to Develop Facts
to Fight Hindsight Bias
The story-building process continues during discovery. Depositions will offer one of
your first opportunities to develop witness
testimony that could mitigate hindsight
bias when presented to a jury. In preparing defense witnesses, it is important to
continue to stress the importance of historical context. For instance, prepare witnesses to testify in a way that will put their
decisions and actions in the appropriate
historical context. Prepare witnesses to
ask for clarification if a plaintiff’s attorney
asks questions that do not refer to a specific time period by asking that attorney
before responding, “What time period are
you asking about?”, or “As of what time?”,
which will prevent the plaintiff’s attorney
from muddling history and will help keep
the record clear.
You should consider engaging in redirect
examinations of company witnesses. This
is a proactive step through which you can
begin to lay the groundwork for a defendant’s story. Even a short redirect examination can develop testimony that humanizes
a witness—something a plaintiffs’ counsel
will have no interest in doing—and hopefully will show that the witness is a real
human being whose decisions or actions
were based on the best available information at the time.
Affirmative discovery can also advance
the defendant’s story. If you can demonstrate that a plaintiff would not have heeded
an additional warning, even if furnished,
that is another way to tackle hindsight bias.
After experiencing a side effect, generally
a plaintiff will claim in hindsight that he
or she would not have taken a drug if he
or she had been warned. The way to defeat
that testimony is to bring up other situations in which a plaintiff ignored warnings
on other products, such as smoking, taking other medications with similar warnings, or using other potentially dangerous
products. If jurors hear that a plaintiff has
a history of ignoring warnings, then they
may approach a plaintiff’s assertions with
skepticism.
Use Jury Selection to Identify Jurors
Susceptible to Hindsight Bias
Jury selection is always critical to a good
defense. When it comes to overcoming
hindsight bias, the jury selection process
presents an important opportunity on at
least two fronts. The first is that you can
use the selection process to begin teaching
jurors the value and importance of overcoming hindsight bias. Lay the issue on
the table. The saying “hindsight is 20/20”
is common, and most jurors will recognize how hindsight bias enters their daily
lives. Use an example of hindsight bias
to bring the issue home. From the very
beginning, tell jurors that their responsibility as fact finders requires viewing the
facts in the appropriate historical context.
18 For The Defense October 2010
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If the standard is whether the manufacturer “knew or should have known” about
a particular harm, then jurors must understand at the outset that the question that
they will decide is tied to a particular point
in time and that the benefit of hindsight
should not sway their verdict. It is difficult
for jurors to talk about abstract concepts,
values, or hypotheticals. It is easier to conduct voir dire by referring to jurors’ personal experiences. Consider questions that
allow jurors to talk with you about their
personal experiences of assessing past conduct. You will note eliminate hindsight bias
by instruction, lecture, or argument. Making jurors aware of hindsight bias and how
it can handicap them in their efforts to
reach a correct result is a big enough challenge during voir dire. Use jurors’ personal
experiences to elicit awareness of hindsight
bias, and recognize that some jurors cannot
realistically practice impartiality, regardless of your efforts to educate them.
That means that the other important
aspect of jury selection is to identify those
jurors who are unwilling or unable to set
aside their biases, including hindsight bias,
to render a fair and impartial verdict. There
are a variety of techniques to gauge a juror’s
susceptibility to hindsight bias. Deciding
which techniques you will use will depend
on the facts of a case. Approaching the
problem directly it is not particularly useful. Asking jurors directly whether they
will be able to overcome hindsight bias
and decide the case based on the information available at the relevant time typically
will elicit politically correct answers about
following the judge’s instructions. The
more reliable window into bias, including
hindsight bias, is to explore relevant personal experiences. So developing voir dire
questions that explore jurors’ experiences
involving hindsight bias can help you to
introduce questions about hindsight bias.
But to be meaningful, you will need to prepare to follow up and probe. Ask a juror
how he or she felt about that event. Did it
result in a fair decision or an unfair decision? What did the juror learn from the
experience, would he or she approach the
situation differently today, and why, or, if
he or she would not change a thing, why
not? For example, you might ask, “Have
you ever made a decision that, based on
information you learned later, you wish
you could take back?” Jurors who have
been hurt by hindsight bias are more likely
to reject it than jurors who have not been
affected by it. If you chose to use some of
your voir dire time on hindsight bias, probe
deeply enough to know whether and how it
has affected jurors in their own lives in real
and concrete terms—not as a mere theory
or hypothetical.
Tackle Hindsight Bias Head-On
During Your Trial
Trial is the time to tell the story of the
case and tackle hindsight bias head-on.
An opening statement should build on
the discussion of hindsight bias from jury
selection but now introduce the facts of a
case. As noted, the key here is to tell the
story so that jurors are transported back
in time and can view the facts through the
eyes of company scientists, safety officers,
and executives who will testify at the trial,
as well as view the plaintiff’s conduct and
the plaintiff’s case through the same lens.
During the part of the trial when the plaintiff’s attorney makes the plaintiff’s case,
use cross-examination when possible to
challenge hindsight bias. For instance, if a
plaintiff’s experts rely on some recent data
to support their opinions, in your crossexamination point out that the data was
not available to company scientists at the
time in question.
In presenting a defendant’s case, it is
important to call live witnesses when possible to put a living human face on a company’s actions. These witnesses should be
capable of discussing in detail the decisions that a company made and the basis
for those decisions at the time. Effective
live witnesses who are able to tell a story
can assist in breaking down prematurely
constructed causal links between a plaintiff’s injury and the product and can help
jurors judge the case from the perspective
of foresight, as opposed to hindsight. Philip
G. Peters, Hindsight Bias and Tort Liability:
Avoiding Premature Conclusions, 31 Ariz.
St. L.J. 1277, 1287 (1999). These witnesses
can contribute to your attempts to recreate
the atmosphere and conditions of a company’s decision-making process before a
plaintiff was injured. Research has shown
that placing jurors in the situation of a
company can mitigate hindsight bias, as
discussed above.
Expert witness testimony can also help
mitigate hindsight bias. Choosing the
right expert—both in terms of credentials
and the ability to connect with jurors and
transport them back in time—is important. A good teacher is far more compelling
than the smartest guy in the room. Because
they do not work for a company, expert witnesses can furnish the perspective of out-
It is important to insist
that the instructions include
language to mitigate
potential hindsight bias.
side observers, commenting on the state
of knowledge at the time of a particular
company decision. If the issue is whether
a company “should have known” of a possible side effect of a drug, an expert can
contrast what is known today with what
was known at the time that the drug was
developed, even highlighting the events
that led to improved knowledge. In this
role, experts can emphasize that scientific
knowledge is constantly advancing and
that it is unfair to judge yesterday’s decisions based on today’s knowledge.
A closing argument then presents yet
another opportunity to communicate the
defendant’s story and to emphasize the
facts and themes developed to mitigate
potential hindsight bias.
Carefully Craft Jury Instructions
Don’t forget the jury instructions. The
words in your closing argument are not
the final words. Jury instructions are the
final words. While most trial lawyers have
mixed feelings at best about jury instructions, these instructions have the potential to play a key role in the deliberation
process. For that reason, it is important
to insist that the instructions include language to mitigate potential hindsight bias.
An obvious example is an explicit instruction that acknowledges the potential for
hindsight bias and advises jurors that they
may not rely on information developed
Hindsight Bias, continued on page 86
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Hindsight Bias, from page 19
after the fact to judge a company’s conduct at a particular point in the past. A less
direct approach is to ask that the instructions refer to the point in time that is relevant to a case. To maximize the effect of
carefully crafting instructions, you might
also consider requesting that jurors receive
preliminary instructions before a trial
begins, which provides yet another opportunity to mitigate potential hindsight bias.
Conclusion
Sacking the Monday morning quarterback
is no easy task. Whether predicting the success of Nixon’s trip to China or sitting on a
jury in a pharmaceutical failure-to-warn
case, the potential for hindsight bias exists
in all of us. As defense attorneys, it is crucial to recognize hindsight bias from the
start and to formulate a strategy that places
a company’s decisions and actions in the
appropriate historical context to mitigate
the bias as much as possible.
86 For The Defense October 2010
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Attachment 2
Attachment 3
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
ACTOS safely and effectively. See full prescribing information for
ACTOS.
ACTOS (pioglitazone) tablets for oral use
Initial U.S. Approval: 1999
WARNING: CONGESTIVE HEART FAILURE
See full prescribing information for complete boxed warning.
• Thiazolidinediones, including ACTOS, cause or exacerbate
congestive heart failure in some patients. (5.1)
•
After initiation of ACTOS, and after dose increases, monitor
patients carefully for signs and symptoms of heart failure
(e.g., excessive, rapid weight gain, dyspnea, and/or edema).
If heart failure develops, it should be managed according to
current standards of care and discontinuation or dose
reduction of ACTOS must be considered. (5.1)
•
ACTOS is not recommended in patients with symptomatic
heart failure. (5.1)
•
Initiation of ACTOS in patients with established New York
Heart Association (NYHA) Class III or IV heart failure is
contraindicated. (4, 5.1)
---------------------------INDICATIONS AND USAGE----------------------------ACTOS is a thiazolidinedione and an agonist for peroxisome
proliferator-activated receptor (PPAR) gamma indicated as an adjunct
to diet and exercise to improve glycemic control in adults with type 2
diabetes mellitus in multiple clinical settings. (1, 14)
Important Limitations of Use:
• Not for treatment of type 1 diabetes or diabetic ketoacidosis. (1)
-----------------------DOSAGE AND ADMINISTRATION----------------------• Initiate ACTOS at 15 mg or 30 mg once daily. Limit initial dose to
15 mg once daily in patients with NYHA Class I or II heart failure.
(2.1)
•
If there is inadequate glycemic control, the dose can be increased
in 15 mg increments up to a maximum of 45 mg once daily. (2.1)
•
Obtain liver tests before starting ACTOS. If abnormal, use caution
when treating with ACTOS, investigate the probable cause, treat (if
possible) and follow appropriately. Monitoring liver tests while on
ACTOS is not recommended in patients without liver disease. (5.3)
----------------------DOSAGE FORMS AND STRENGTHS--------------------Tablets: 15 mg, 30 mg, and 45 mg (3)
------------------------------CONTRAINDICATIONS-------------------------------• Initiation in patients with established New York Heart Association
(NYHA) Class III or IV heart failure [see Boxed Warning]. (4)
•
Use in patients with known hypersensitivity to pioglitazone or any
other component of ACTOS. (4)
-------------------------WARNINGS AND PRECAUTIONS---------------------• Congestive heart failure: Fluid retention may occur and can
exacerbate or lead to congestive heart failure. Combination use
with insulin and use in congestive heart failure NYHA Class I and II
may increase risk. Monitor patients for signs and symptoms. (5.1)
•
Hypoglycemia: When used with insulin or an insulin secretagogue,
a lower dose of the insulin or insulin secretagogue may be needed
to reduce the risk of hypoglycemia. (5.2)
•
Hepatic effects: Postmarketing reports of hepatic failure, sometimes
fatal. Causality cannot be excluded. If liver injury is detected,
promptly interrupt ACTOS and assess patient for probable cause,
then treat cause if possible, to resolution or stabilization. Do not
restart ACTOS if liver injury is confirmed and no alternate etiology
can be found. (5.3)
•
Bladder cancer: Preclinical and clinical trial data, and results from
an observational study suggest an increased risk of bladder cancer
in pioglitazone users. The observational data further suggest that
the risk increases with duration of use. Do not use in patients with
active bladder cancer. Use caution when using in patients with a
prior history of bladder cancer (5.4)
•
Edema: Dose-related edema may occur. (5.5)
•
Fractures: Increased incidence in female patients. Apply current
standards of care for assessing and maintaining bone health. (5.6)
•
Macular edema: Postmarketing reports. Recommend regular eye
exams in all patients with diabetes according to current standards
of care with prompt evaluation for acute visual changes. (5.7)
•
Macrovascular outcomes: There have been no clinical studies
establishing conclusive evidence of macrovascular risk reduction
with ACTOS or any other antidiabetic drug. (5.9)
--------------------------------ADVERSE REACTIONS----------------------------Most common adverse reactions (≥5%) are upper respiratory tract
infection, headache, sinusitis, myalgia, and pharyngitis. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Takeda
Pharmaceuticals at 1-877-825-3327 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
----------------------------------DRUG INTERACTIONS---------------------------•
Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone
concentrations. Limit ACTOS dose to 15 mg daily. (2.3, 7.1)
•
CYP2C8 inducers (e.g., rifampin) may decrease pioglitazone
concentrations. (7.2)
-------------------------USE IN SPECIFIC POPULATIONS---------------------•
Nursing mothers: Discontinue drug or nursing, taking into
consideration the importance of the drug to the mother (8.3)
•
Pediatrics: Not recommended for use in pediatric patients. (8.4)
See 17 for PATIENT COUNSELING INFORMATION and
Medication Guide
Revised: 11/2013
FULL PRESCRIBING INFORMATION: CONTENTS*
1
INDICATIONS AND USAGE
2
DOSAGE AND ADMINISTRATION
2.1 Recommendations for All Patients
2.2 Concomitant Use with an Insulin Secretagogue or Insulin
2.3 Concomitant Use with Strong CYP2C8 Inhibitors
3
DOSAGE FORMS AND STRENGTHS
4
CONTRAINDICATIONS
5
WARNINGS AND PRECAUTIONS
5.1 Congestive Heart Failure
5.2 Hypoglycemia
5.3 Hepatic Effects
5.4 Urinary Bladder Tumors
5.5 Edema
5.6 Fractures
5.7 Macular Edema
5.8 Ovulation
5.9 Macrovascular Outcomes
6
ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7
DRUG INTERACTIONS
7.1 Strong CYP2C8 Inhibitors
8
10
11
12
13
14
16
17
7.2 CYP2C8 Inducers
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
OVERDOSAGE
DESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
CLINICAL STUDIES
14.1 Monotherapy
14.2 Combination Therapy
HOW SUPPLIED/ STORAGE AND HANDLING
PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information
are not listed.
Page 3 of 42
FULL PRESCRIBING INFORMATION
•
•
•
•
1
Thiazolidinediones, including ACTOS, cause or exacerbate congestive
heart failure in some patients [see Warnings and Precautions (5.1)].
After initiation of ACTOS, and after dose increases, monitor patients
carefully for signs and symptoms of heart failure (e.g., excessive, rapid
weight gain, dyspnea, and/or edema). If heart failure develops, it should be
managed according to current standards of care and discontinuation or
dose reduction of ACTOS must be considered.
ACTOS is not recommended in patients with symptomatic heart failure.
Initiation of ACTOS in patients with established New York Heart
Association (NYHA) Class III or IV heart failure is contraindicated [see
Contraindications (4) and Warnings and Precautions (5.1)].
INDICATIONS AND USAGE
Monotherapy and Combination Therapy
ACTOS is indicated as an adjunct to diet and exercise to improve glycemic control in
adults with type 2 diabetes mellitus in multiple clinical settings [see Clinical Studies
(14)].
Important Limitations of Use
ACTOS exerts its antihyperglycemic effect only in the presence of endogenous insulin.
ACTOS should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would
not be effective in these settings.
Use caution in patients with liver disease [see Warnings and Precautions (5.3)].
2
DOSAGE AND ADMINISTRATION
2.1 Recommendations for All Patients
ACTOS should be taken once daily and can be taken without regard to meals.
The recommended starting dose for patients without congestive heart failure is 15 mg or
30 mg once daily.
The recommended starting dose for patients with congestive heart failure (NYHA Class
I or II) is 15 mg once daily.
The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily
based on glycemic response as determined by HbA1c.
After initiation of ACTOS or with dose increase, monitor patients carefully for adverse
reactions related to fluid retention such as weight gain, edema, and signs and
symptoms of congestive heart failure [see Boxed Warning and Warnings and
Precautions (5.5)].
Page 4 of 42
Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and
total bilirubin) should be obtained prior to initiating ACTOS. Routine periodic monitoring
of liver tests during treatment with ACTOS is not recommended in patients without liver
disease. Patients who have liver test abnormalities prior to initiation of ACTOS or who
are found to have abnormal liver tests while taking ACTOS should be managed as
described under Warnings and Precautions [see Warnings and Precautions (5.3) and
Clinical Pharmacology (12.3)].
2.2 Concomitant Use with an Insulin Secretagogue or Insulin
If hypoglycemia occurs in a patient co-administered ACTOS and an insulin
secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be
reduced.
If hypoglycemia occurs in a patient co-administered ACTOS and insulin, the dose of
insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose
should be individualized based on glycemic response.
2.3 Concomitant Use with Strong CYP2C8 Inhibitors
Coadministration of ACTOS and gemfibrozil, a strong CYP2C8 inhibitor, increases
pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended
dose of ACTOS is 15 mg daily when used in combination with gemfibrozil or other
strong CYP2C8 inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology
(12.3)].
3
DOSAGE FORMS AND STRENGTHS
Round tablet contains pioglitazone as follows:
• 15 mg: White to off-white, debossed with “ACTOS” on one side and “15” on the other
4
5
CONTRAINDICATIONS
•
Initiation in patients with established NYHA Class III or IV heart failure [see
Boxed Warning].
•
Use in patients with known hypersensitivity to pioglitazone or any other
component of ACTOS.
WARNINGS AND PRECAUTIONS
5.1 Congestive Heart Failure
ACTOS, like other thiazolidinediones, can cause dose-related fluid retention when used
alone or in combination with other antidiabetic medications and is most common when
ACTOS is used in combination with insulin. Fluid retention may lead to or exacerbate
congestive heart failure. Patients should be observed for signs and symptoms of
congestive heart failure. If congestive heart failure develops, it should be managed
according to current standards of care and discontinuation or dose reduction of ACTOS
must be considered [see Boxed Warning, Contraindications (4), and Adverse Reactions
(6.1)].
Page 5 of 42
5.2 Hypoglycemia
Patients receiving ACTOS in combination with insulin or other antidiabetic medications
(particularly insulin secretagogues such as sulfonylureas) may be at risk for
hypoglycemia. A reduction in the dose of the concomitant antidiabetic medication may
be necessary to reduce the risk of hypoglycemia [see Dosage and Administration (2.2)].
5.3 Hepatic Effects
There have been postmarketing reports of fatal and non-fatal hepatic failure in patients
taking ACTOS, although the reports contain insufficient information necessary to
establish the probable cause. There has been no evidence of drug-induced
hepatotoxicity in the ACTOS controlled clinical trial database to date [see Adverse
Reactions (6.1)].
Patients with type 2 diabetes may have fatty liver disease or cardiac disease with
episodic congestive heart failure, both of which may cause liver test abnormalities, and
they may also have other forms of liver disease, many of which can be treated or
managed. Therefore, obtaining a liver test panel (serum alanine aminotransferase
[ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin) and
assessing the patient is recommended before initiating ACTOS therapy. In patients with
abnormal liver tests, ACTOS should be initiated with caution.
Measure liver tests promptly in patients who report symptoms that may indicate liver
injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or
jaundice. In this clinical context, if the patient is found to have abnormal liver tests (ALT
greater than 3 times the upper limit of the reference range), ACTOS treatment should
be interrupted and investigation done to establish the probable cause. ACTOS should
not be restarted in these patients without another explanation for the liver test
abnormalities.
Patients who have serum ALT greater than three times the reference range with serum
total bilirubin greater than two times the reference range without alternative etiologies
are at risk for severe drug-induced liver injury, and should not be restarted on ACTOS.
For patients with lesser elevations of serum ALT or bilirubin and with an alternate
probable cause, treatment with ACTOS can be used with caution.
5.4 Urinary Bladder Tumors
Tumors were observed in the urinary bladder of male rats in the two-year
carcinogenicity study [see Nonclinical Toxicology (13.1)]. In two 3-year trials in which
ACTOS was compared to placebo or glyburide, there were 16/3656 (0.44%) reports of
bladder cancer in patients taking ACTOS compared to 5/3679 (0.14%) in patients not
taking ACTOS. After excluding patients in whom exposure to study drug was less than
one year at the time of diagnosis of bladder cancer, there were six (0.16%) cases on
ACTOS and two (0.05%) cases on placebo.
A five-year interim report of an ongoing 10-year observational cohort study found a nonsignificant increase in the risk for bladder cancer in subjects ever exposed to ACTOS,
compared to subjects never exposed to ACTOS (HR 1.2 [95% CI 0.9 −1.5]). Compared
to never exposure, a duration of ACTOS therapy longer than 12 months was associated
with an increase in risk (HR 1.4 [95% CI 0.9 −2.1]), which reached statistical
significance after more than 24 months of ACTOS use (HR 1.4 [95% CI 1.03 −2.0]).
Interim results from this study suggested that taking ACTOS longer than 12 months
Page 6 of 42
increased the relative risk of developing bladder cancer in any given year by 40% which
equates to an absolute increase of three cases in 10,000 (from approximately seven in
10,000 [without ACTOS] to approximately 10 in 10,000 [with ACTOS]).
There are insufficient data to determine whether pioglitazone is a tumor promoter for
urinary bladder tumors. Consequently, ACTOS should not be used in patients with
active bladder cancer and the benefits of glycemic control versus unknown risks for
cancer recurrence with ACTOS should be considered in patients with a prior history of
bladder cancer.
5.5 Edema
In controlled clinical trials, edema was reported more frequently in patients treated with
ACTOS than in placebo-treated patients and is dose-related [see Adverse Reactions
(6.1)]. In postmarketing experience, reports of new onset or worsening edema have
been received.
ACTOS should be used with caution in patients with edema. Because
thiazolidinediones, including ACTOS, can cause fluid retention, which can exacerbate or
lead to congestive heart failure, ACTOS should be used with caution in patients at risk
for congestive heart failure. Patients treated with ACTOS should be monitored for signs
and symptoms of congestive heart failure [see Boxed Warning, Warnings and
Precautions (5.1) and Patient Counseling Information (17)].
5.6 Fractures
In PROactive (the Prospective Pioglitazone Clinical Trial in Macrovascular Events),
5238 patients with type 2 diabetes and a history of macrovascular disease were
randomized to ACTOS (N=2605), force-titrated up to 45 mg daily or placebo (N=2633)
in addition to standard of care. During a mean follow-up of 34.5 months, the incidence
of bone fracture in females was 5.1% (44/870) for ACTOS versus 2.5% (23/905) for
placebo. This difference was noted after the first year of treatment and persisted during
the course of the study. The majority of fractures observed in female patients were
nonvertebral fractures including lower limb and distal upper limb. No increase in the
incidence of fracture was observed in men treated with ACTOS (1.7%) versus placebo
(2.1%). The risk of fracture should be considered in the care of patients, especially
female patients, treated with ACTOS and attention should be given to assessing and
maintaining bone health according to current standards of care.
5.7 Macular Edema
Macular edema has been reported in postmarketing experience in diabetic patients who
were taking ACTOS or another thiazolidinedione. Some patients presented with blurred
vision or decreased visual acuity, but others were diagnosed on routine ophthalmologic
examination.
Most patients had peripheral edema at the time macular edema was diagnosed. Some
patients had improvement in their macular edema after discontinuation of the
thiazolidinedione.
Patients with diabetes should have regular eye exams by an ophthalmologist according
to current standards of care. Patients with diabetes who report any visual symptoms
should be promptly referred to an ophthalmologist, regardless of the patient's underlying
medications or other physical findings [see Adverse Reactions (6.1)].
Page 7 of 42
5.8 Ovulation
Therapy with ACTOS, like other thiazolidinediones, may result in ovulation in some
premenopausal anovulatory women. As a result, these patients may be at an increased
risk for pregnancy while taking ACTOS [see Use in Specific Populations (8.1)]. This
effect has not been investigated in clinical trials, so the frequency of this occurrence is
not known. Adequate contraception in all premenopausal women treated with ACTOS is
recommended.
5.9 Macrovascular Outcomes
There have been no clinical studies establishing conclusive evidence of macrovascular
risk reduction with ACTOS or any other antidiabetic drug.
6
ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling:
•
•
•
Congestive heart failure [see Boxed Warning and Warnings and Precautions (5.1)]
Edema [see Warnings and Precautions (5.5)]
Fractures [see Warnings and Precautions (5.6)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates observed in practice.
Over 8500 patients with type 2 diabetes have been treated with ACTOS in randomized,
double-blind, controlled clinical trials, including 2605 patients with type 2 diabetes and
macrovascular disease treated with ACTOS in the PROactive clinical trial. In these
trials, over 6000 patients have been treated with ACTOS for six months or longer, over
4500 patients have been treated with ACTOS for one year or longer, and over 3000
patients have been treated with ACTOS for at least two years.
In six pooled 16- to 26-week placebo-controlled monotherapy and 16- to 24-week addon combination therapy trials, the incidence of withdrawals due to adverse events was
4.5% for patients treated with ACTOS and 5.8% for comparator-treated patients. The
most common adverse events leading to withdrawal were related to inadequate
glycemic control, although the incidence of these events was lower (1.5%) with ACTOS
than with placebo (3.0%).
In the PROactive trial, the incidence of withdrawals due to adverse events was 9.0% for
patients treated with ACTOS and 7.7% for placebo-treated patients. Congestive heart
failure was the most common serious adverse event leading to withdrawal occurring in
1.3% of patients treated with ACTOS and 0.6% of patients treated with placebo.
Page 8 of 42
Common Adverse Events: 16- to 26-Week Monotherapy Trials
A summary of the incidence and type of common adverse events reported in three
pooled 16- to 26-week placebo-controlled monotherapy trials of ACTOS is provided in
Table 1. Terms that are reported represent those that occurred at an incidence of >5%
and more commonly in patients treated with ACTOS than in patients who received
placebo. None of these adverse events were related to ACTOS dose.
Table 1. Three Pooled 16- to 26-Week Placebo-Controlled Clinical Trials of
ACTOS Monotherapy: Adverse Events Reported at an Incidence
>5% and More Commonly in Patients Treated with ACTOS than in
Patients Treated with Placebo
% of Patients
Placebo
N=259
ACTOS
N=606
Upper Respiratory Tract Infection
8.5
13.2
Headache
6.9
9.1
Sinusitis
4.6
6.3
Myalgia
2.7
5.4
Pharyngitis
0.8
5.1
Page 9 of 42
Common Adverse Events: 16- to 24-Week Add-on Combination Therapy Trials
A summary of the overall incidence and types of common adverse events reported in
trials of ACTOS add-on to sulfonylurea is provided in Table 2. Terms that are reported
represent those that occurred at an incidence of >5% and more commonly with the
highest tested dose of ACTOS.
Table 2. 16- to 24-Week Clinical Trials of ACTOS Add-on to Sulfonylurea
16-Week Placebo-Controlled Trial
Adverse Events Reported in >5% of Patients and More
Commonly in Patients Treated with ACTOS 30 mg
+ Sulfonylurea than in Patients Treated with Placebo
+ Sulfonylurea
% of Patients
Placebo
+ Sulfonylurea
N=187
ACTOS 15 mg
+ Sulfonylurea
N=184
ACTOS 30 mg
+ Sulfonylurea
N=189
Edema
2.1
1.6
12.7
Headache
3.7
4.3
5.3
Flatulence
0.5
2.7
6.3
0
2.7
5.3
Weight Increased
24-Week Non-Controlled Double-Blind Trial
Adverse Events Reported in >5% of Patients and More
Commonly in Patients Treated with ACTOS 45 mg
+ Sulfonylurea than in Patients Treated with ACTOS
30 mg + Sulfonylurea
% of Patients
ACTOS 30 mg
+ Sulfonylurea
N=351
ACTOS 45 mg
+ Sulfonylurea
N=351
Hypoglycemia
13.4
15.7
Edema
10.5
23.1
Upper Respiratory
Tract Infection
12.3
14.8
Weight Increased
9.1
13.4
Urinary Tract Infection
5.7
6.8
Note: The preferred terms of edema peripheral, generalized edema, pitting edema and fluid
retention were combined to form the aggregate term of “edema.”
Page 10 of 42
trials of ACTOS add-on to metformin is provided in Table 3. Terms that are reported
represent those that occurred at an incidence of >5% and more commonly with the
highest tested dose of ACTOS.
Table 3. 16- to 24-Week Clinical Trials of ACTOS Add-on to Metformin
Adverse Events Reported in >5% of Patients
and More Commonly in Patients Treated with
ACTOS + Metformin than in Patients Treated
with Placebo + Metformin
% of Patients
Placebo
+ Metformin
N=160
ACTOS 30 mg
+ Metformin
N=168
Edema
2.5
6.0
Headache
1.9
6.0
Adverse Events Reported in >5% of Patients
and More Commonly in Patients Treated with
ACTOS 45 mg + Metformin than in Patients
Treated with ACTOS 30 mg + Metformin
% of Patients
ACTOS 30 mg
+ Metformin
N=411
ACTOS 45 mg
+ Metformin
N=416
12.4
13.5
Edema
5.8
13.9
Headache
5.4
5.8
Weight Increased
2.9
6.7
Upper Respiratory Tract
Infection
Page 11 of 42
Table 4 summarizes the incidence and types of common adverse events reported in
trials of ACTOS add-on to insulin. Terms that are reported represent those that occurred
at an incidence of >5% and more commonly with the highest tested dose of ACTOS.
Table 4. 16- to 24-Week Clinical Trials of ACTOS Add-on to Insulin
Adverse Events Reported in >5% of Patients and
More Commonly in Patients Treated with ACTOS
30 mg + Insulin than in Patients Treated with
Placebo + Insulin
Placebo
+ Insulin
N=187
% of Patients
ACTOS 15 mg
+ Insulin
N=191
ACTOS 30 mg
+ Insulin
N=188
Hypoglycemia
4.8
7.9
15.4
Edema
7.0
12.6
17.6
Upper Respiratory Tract Infection
9.6
8.4
14.9
Headache
3.2
3.1
6.9
Weight Increased
0.5
5.2
6.4
Back Pain
4.3
2.1
5.3
Dizziness
3.7
2.6
5.3
Flatulence
1.6
3.7
5.3
Adverse Events Reported in >5% of Patients and
More Commonly in Patients Treated with
ACTOS 45 mg + Insulin than in Patients Treated
with ACTOS 30 mg + Insulin
% of Patients
ACTOS 30 mg
+ Insulin
N=345
43.5
ACTOS 45 mg
+ Insulin
N=345
47.8
22.0
26.1
Weight Increased
7.2
13.9
Urinary Tract Infection
4.9
8.7
Diarrhea
5.5
5.8
Back Pain
3.8
6.4
Blood Creatine Phosphokinase
Increased
4.6
5.5
Sinusitis
4.6
5.5
Hypertension
4.1
5.5
Hypoglycemia
Edema
Note: The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were
combined to form the aggregate term of “edema.”
Page 12 of 42
the PROactive trial is provided in Table 5. Terms that are reported represent those that
occurred at an incidence of >5% and more commonly in patients treated with ACTOS
than in patients who received placebo.
Table 5. PROactive Trial: Incidence and Types of Adverse Events Reported
in >5% of Patients Treated with ACTOS and More Commonly than
Placebo
% of Patients
Placebo
N=2633
ACTOS
N=2605
Hypoglycemia
18.8
27.3
Edema
15.3
26.7
Cardiac Failure
6.1
8.1
Pain in Extremity
5.7
6.4
Back Pain
5.1
5.5
Chest Pain
5.0
5.1
Mean duration of patient follow-up was 34.5 months.
Page 13 of 42
Congestive Heart Failure
A summary of the incidence of adverse events related to congestive heart failure is
provided in Table 6 for the 16- to 24-week add-on to sulfonylurea trials, for the 16- to
24-week add-on to insulin trials, and for the 16- to 24-week add-on to metformin trials.
None of the events were fatal.
Table 6. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF)
Patients Treated with ACTOS or Placebo Added on to a Sulfonylurea
Number (%) of Patients
Non-Controlled
Double-Blind Trial
(24 weeks)
Placebo-Controlled Trial
(16 weeks)
At least one
congestive heart
failure event
Hospitalized
Placebo
+ Sulfonylurea
N=187
ACTOS 15 mg
+ Sulfonylurea
N=184
ACTOS 30 mg
+ Sulfonylurea
N=189
ACTOS 30 mg
+ Sulfonylurea
N=351
ACTOS 45 mg
+ Sulfonylurea
N=351
2 (1.1%)
0
0
1 (0.3%)
6 (1.7%)
2 (1.1%)
0
0
0
2 (0.6%)
Patients Treated with ACTOS or Placebo Added on to Insulin
Non-Controlled
Double-Blind Trial
(24 weeks)
(16 weeks)
At least one
congestive heart
failure event
Hospitalized
Placebo
+ Insulin
N=187
ACTOS 15 mg
+ Insulin
N=191
ACTOS 30 mg
+ Insulin
N=188
ACTOS 30 mg
+ Insulin
N=345
ACTOS 45 mg
+ Insulin
N=345
0
2 (1.0%)
2 (1.1%)
3 (0.9%)
5 (1.4%)
0
2 (1.0%)
1 (0.5%)
1 (0.3%)
3 (0.9%)
Patients Treated with ACTOS or Placebo Added on to Metformin
(16 weeks)
Non-Controlled
Double-Blind Trial
(24 weeks)
Placebo
+ Metformin
N=160
ACTOS 30 mg
+ Metformin
N=168
ACTOS 30 mg
+ Metformin
N=411
ACTOS 45 mg
+ Metformin
N=416
At least one
congestive heart
failure event
0
1 (0.6%)
0
1 (0.2%)
Hospitalized
0
1 (0.6%)
0
1 (0.2%)
Page 14 of 42
Patients with type 2 diabetes and NYHA class II or early class III congestive heart
failure were randomized to receive 24 weeks of double-blind treatment with either
ACTOS at daily doses of 30 mg to 45 mg (n=262) or glyburide at daily doses of 10 mg
to 15 mg (n=256). A summary of the incidence of adverse events related to congestive
heart failure reported in this study is provided in Table 7.
Table 7. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF)
in Patients with NYHA Class II or III Congestive Heart Failure Treated
with ACTOS or Glyburide
Number (%) of Subjects
ACTOS
N=262
Glyburide
N=256
5 (1.9%)
6 (2.3%)
Overnight hospitalization for worsening CHF
(adjudicated)
26 (9.9%)
12 (4.7%)
Emergency room visit for CHF (adjudicated)
4 (1.5%)
3 (1.2%)
35 (13.4%)
21 (8.2%)
Death due to cardiovascular causes (adjudicated)
Patients experiencing CHF progression during
study
Congestive heart failure events leading to hospitalization that occurred during the
PROactive trial are summarized in Table 8.
Table 8. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF) in
PROactive Trial
Placebo
N=2633
ACTOS
N=2605
108 (4.1%)
149 (5.7%)
Fatal
22 (0.8%)
25 (1.0%)
Hospitalized, nonfatal
86 (3.3%)
124 (4.7%)
At least one hospitalized congestive heart failure event
Cardiovascular Safety
In the PROactive trial, 5238 patients with type 2 diabetes and a history of
macrovascular disease were randomized to ACTOS (N=2605), force-titrated up to
45 mg daily or placebo (N=2633) in addition to standard of care. Almost all patients
(95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors,
angiotensin II receptor blockers, calcium channel blockers, nitrates, diuretics, aspirin,
statins and fibrates). At baseline, patients had a mean age of 62 years, mean duration
of diabetes of 9.5 years, and mean HbA1c of 8.1%. Mean duration of follow-up was 34.5
months.
The primary objective of this trial was to examine the effect of ACTOS on mortality and
macrovascular morbidity in patients with type 2 diabetes mellitus who were at high risk
for macrovascular events. The primary efficacy variable was the time to the first
occurrence of any event in a cardiovascular composite endpoint that included all-cause
mortality, nonfatal myocardial infarction (MI) including silent MI, stroke, acute coronary
Page 15 of 42
syndrome, cardiac intervention including coronary artery bypass grafting or
percutaneous intervention, major leg amputation above the ankle, and bypass surgery
or revascularization in the leg. A total of 514 (19.7%) patients treated with ACTOS and
572 (21.7%) placebo-treated patients experienced at least one event from the primary
composite endpoint (hazard ratio 0.90; 95% Confidence Interval: 0.80, 1.02; p=0.10).
Although there was no statistically significant difference between ACTOS and placebo
for the three-year incidence of a first event within this composite, there was no increase
in mortality or in total macrovascular events with ACTOS. The number of first
occurrences and total individual events contributing to the primary composite endpoint
is shown in Table 9.
Table 9. PROactive: Number of First and Total Events for Each Component within the
Cardiovascular Composite Endpoint
Cardiovascular Events
Placebo
N=2633
ACTOS
N=2605
572 (21.7)
Total
events
n
900
514 (19.7)
Total
events
n
803
122 (4.6)
186
110 (4.2)
177
Nonfatal myocardial infarction
(MI)
118 (4.5)
157
105 (4.0)
131
Stroke
96 (3.6)
119
76 (2.9)
92
Acute coronary syndrome
63 (2.4)
78
42 (1.6)
65
Cardiac intervention
(CABG/PCI)
101 (3.8)
240
101 (3.9)
195
Major leg amputation
15 (0.6)
28
9 (0.3)
28
Leg revascularization
57 (2.2)
92
71 (2.7)
115
Any event
All-cause mortality
First Events
n (%)
First Events
n (%)
CABG = coronary artery bypass grafting; PCI = percutaneous intervention
Page 16 of 42
Weight Gain
Dose-related weight gain occurs when ACTOS is used alone or in combination with
other antidiabetic medications. The mechanism of weight gain is unclear but probably
involves a combination of fluid retention and fat accumulation.
Tables 10 and 11 summarize the changes in body weight with ACTOS and placebo in
the 16- to 26-week randomized, double-blind monotherapy and 16- to 24-week
combination add-on therapy trials and in the PROactive trial.
Table 10. Weight Changes (kg) from Baseline During Randomized, Double-Blind Clinical Trials
Control Group
(Placebo)
Median
th
th
(25 /75
percentile)
-1.4 (-2.7/0.0)
N=256
ACTOS
15 mg
Median
th
th
(25 /75
percentile)
0.9 (-0.5/3.4)
N=79
ACTOS
30 mg
Median
th
th
(25 /75
percentile)
1.0 (-0.9/3.4)
N=188
ACTOS
45 mg
Median
th
th
(25 /75
percentile)
2.6 (0.2/5.4)
N=79
Sulfonylurea
-0.5 (-1.8/0.7)
N=187
2.0 (0.2/3.2)
N=183
3.1 (1.1/5.4)
N=528
Metformin
-1.4 (-3.2/0.3)
N=160
N/A
0.9 (-1.3/3.2)
N=567
4.1 (1.8/7.3)
N=333
1.8 (-0.9/5.0)
N=407
Insulin
0.2 (-1.4/1.4)
N=182
2.3 (0.5/4.3)
N=190
3.3 (0.9/6.3)
N=522
4.1 (1.4/6.8)
N=338
Monotherapy
(16 to 26 weeks)
Combination
Therapy
(16 to 24 weeks)
Table 11. Median Change in Body Weight in Patients Treated with ACTOS Versus Patients
Treated with Placebo During the Double-Blind Treatment Period in the PROactive Trial
Change from baseline to final visit (kg)
Placebo
ACTOS
Median
th
th
(25 /75
percentile)
Median
th
th
(25 /75
percentile)
-0.5 (-3.3, 2.0)
N=2581
+3.6 (0.0, 7.5)
N=2560
Note: Median exposure for both ACTOS and Placebo was 2.7 years.
Page 17 of 42
Edema
Edema induced from taking ACTOS is reversible when ACTOS is discontinued. The
edema usually does not require hospitalization unless there is coexisting congestive
heart failure. A summary of the frequency and types of edema adverse events occurring
in clinical investigations of ACTOS is provided in Table 12.
Table 12. Adverse Events of Edema in Patients Treated with ACTOS
Monotherapy (16 to 26 weeks)
Sulfonylurea
Combined Therapy
Metformin
(16 to 24 weeks)
Insulin
Placebo
ACTOS
15 mg
ACTOS
30 mg
ACTOS
45 mg
3 (1.2%)
N=259
2 (2.5%)
N= 81
13 (4.7%)
N= 275
11 (6.5%)
N=169
4 (2.1%)
N=187
3 (1.6%)
N=184
61 (11.3%)
N=540
81 (23.1%)
N=351
4 (2.5%)
N=160
N/A
34 (5.9%)
N=579
58 (13.9%)
N=416
13 (7.0%)
N=187
24 (12.6%)
N=191
109 (20.5%)
N=533
90 (26.1%)
N=345
Table 13. Adverse Events of Edema in Patients in the PROactive Trial
Placebo
N=2633
ACTOS
N=2605
419 (15.9%)
712 (27.3%)
Hepatic Effects
There has been no evidence of induced hepatotoxicity with ACTOS in the ACTOS
controlled clinical trial database to date. One randomized, double-blind 3-year trial
comparing ACTOS to glyburide as add-on to metformin and insulin therapy was
specifically designed to evaluate the incidence of serum ALT elevation to greater than
three times the upper limit of the reference range, measured every eight weeks for the
first 48 weeks of the trial then every 12 weeks thereafter. A total of 3/1051 (0.3%)
patients treated with ACTOS and 9/1046 (0.9%) patients treated with glyburide
developed ALT values greater than three times the upper limit of the reference range.
None of the patients treated with ACTOS in the ACTOS controlled clinical trial database
to date have had a serum ALT greater than three times the upper limit of the reference
range and a corresponding total bilirubin greater than two times the upper limit of the
Page 18 of 42
reference range, a combination predictive of the potential for severe drug-induced liver
injury.
Hypoglycemia
In the ACTOS clinical trials, adverse events of hypoglycemia were reported based on
clinical judgment of the investigators and did not require confirmation with fingerstick
glucose testing.
In the 16-week add-on to sulfonylurea trial, the incidence of reported hypoglycemia was
3.7% with ACTOS 30 mg and 0.5% with placebo. In the 16-week add-on to insulin trial,
the incidence of reported hypoglycemia was 7.9% with ACTOS 15 mg, 15.4% with
ACTOS 30 mg, and 4.8% with placebo.
The incidence of reported hypoglycemia was higher with ACTOS 45 mg compared to
ACTOS 30 mg in both the 24-week add-on to sulfonylurea trial (15.7% vs. 13.4%) and
in the 24-week add-on to insulin trial (47.8% vs. 43.5%).
Three patients in these four trials were hospitalized due to hypoglycemia. All three
patients were receiving ACTOS 30 mg (0.9%) in the 24-week add-on to insulin trial. An
additional 14 patients reported severe hypoglycemia (defined as causing considerable
interference with patient’s usual activities) that did not require hospitalization. These
patients were receiving ACTOS 45 mg in combination with sulfonylurea (n=2) or ACTOS
30 mg or 45 mg in combination with insulin (n=12).
Urinary Bladder Tumors
Tumors were observed in the urinary bladder of male rats in the two-year
carcinogenicity study [see Nonclinical Toxicology (13.1)]. In two 3-year trials in which
ACTOS was compared to placebo or glyburide, there were 16/3656 (0.44%) reports of
bladder cancer in patients taking ACTOS compared to 5/3679 (0.14%) in patients not
taking ACTOS. After excluding patients in whom exposure to study drug was less than
one year at the time of diagnosis of bladder cancer, there were six (0.16%) cases on
ACTOS and two (0.05%) cases on placebo. There are too few events of bladder cancer
to establish causality.
Laboratory Abnormalities
Hematologic Effects
ACTOS may cause decreases in hemoglobin and hematocrit. In placebo-controlled
monotherapy trials, mean hemoglobin values declined by 2% to 4% in patients treated
with ACTOS compared with a mean change in hemoglobin of -1% to +1% in placebotreated patients. These changes primarily occurred within the first 4 to 12 weeks of
therapy and remained relatively constant thereafter. These changes may be related to
increased plasma volume associated with ACTOS therapy and are not likely to be
associated with any clinically significant hematologic effects.
Creatine Phosphokinase
During protocol-specified measurement of serum creatine phosphokinase (CPK) in
ACTOS clinical trials, an isolated elevation in CPK to greater than 10 times the upper
limit of the reference range was noted in nine (0.2%) patients treated with ACTOS
(values of 2150 to 11400 IU/L) and in no comparator-treated patients. Six of these nine
patients continued to receive ACTOS, two patients were noted to have the CPK
elevation on the last day of dosing and one patient discontinued ACTOS due to the
Page 19 of 42
elevation. These elevations resolved without any apparent clinical sequelae. The
relationship of these events to ACTOS therapy is unknown.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of
ACTOS. Because these reactions are reported voluntarily from a population of uncertain
size, it is generally not possible to reliably estimate their frequency or establish a causal
relationship to drug exposure.
•
•
New onset or worsening diabetic macular edema with decreased visual acuity [see
Warnings and Precautions (5.7)].
Fatal and nonfatal hepatic failure [see Warnings and Precautions (5.3)].
Postmarketing reports of congestive heart failure have been reported in patients treated
with ACTOS, both with and without previously known heart disease and both with and
without concomitant insulin administration.
In postmarketing experience, there have been reports of unusually rapid increases in
weight and increases in excess of that generally observed in clinical trials. Patients who
experience such increases should be assessed for fluid accumulation and volumerelated events such as excessive edema and congestive heart failure [see Boxed
Warning and Warnings and Precautions (5.1)].
7
DRUG INTERACTIONS
7.1 Strong CYP2C8 Inhibitors
An inhibitor of CYP2C8 (e.g., gemfibrozil) significantly increases the exposure (area
under the serum concentration-time curve or AUC) and half-life (t½) of pioglitazone.
Therefore, the maximum recommended dose of ACTOS is 15 mg daily if used in
combination with gemfibrozil or other strong CYP2C8 inhibitors [see Dosage and
Administration (2.3) and Clinical Pharmacology (12.3)].
7.2 CYP2C8 Inducers
An inducer of CYP2C8 (e.g., rifampin) may significantly decrease the exposure (AUC)
of pioglitazone. Therefore, if an inducer of CYP2C8 is started or stopped during
treatment with ACTOS, changes in diabetes treatment may be needed based on clinical
response without exceeding the maximum recommended daily dose of 45 mg for
ACTOS [see Clinical Pharmacology (12.3)].
8
8.1
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C.
There are no adequate and well-controlled studies of ACTOS in pregnant women.
Animal studies show increased rates of post-implantation loss, delayed development,
reduced fetal weights, and delayed parturition at doses 10 to 40 times the maximum
recommended human dose. ACTOS should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Clinical Considerations
Abnormal blood glucose concentrations during pregnancy are associated with a higher
incidence of congenital anomalies, as well as increased neonatal morbidity and
Page 20 of 42
mortality. Most experts recommend the use of insulin during pregnancy to maintain
blood glucose concentrations as close to normal as possible for patients with diabetes.
Animal Data
In animal reproductive studies, pregnant rats and rabbits received pioglitazone at doses
up to approximately 17 (rat) and 40 (rabbit) times the maximum recommended human
oral dose (MRHD) based on body surface area (mg/m2); no teratogenicity was
observed. Increases in embryotoxicity (increased postimplantation losses, delayed
development, reduced fetal weights, and delayed parturition) occurred in rats that
received oral doses approximately 10 or more times the MRHD (mg/m2 basis). No
functional or behavioral toxicity was observed in rat offspring. When pregnant rats
received pioglitazone during late gestation and lactation, delayed postnatal
development, attributed to decreased body weight, occurred in rat offspring at oral
maternal doses approximately two or more times the MRHD (mg/m2 basis). In rabbits,
embryotoxicity occurred at oral doses approximately 40 times the MRHD (mg/m2 basis).
8.3 Nursing Mothers
It is not known whether ACTOS is secreted in human milk. Pioglitazone is secreted in
the milk of lactating rats. Because many drugs are excreted in human milk, and
because of the potential for ACTOS to cause serious adverse reactions in nursing
infants, a decision should be made to discontinue nursing or discontinue ACTOS, taking
into account the importance of ACTOS to the mother.
8.4 Pediatric Use
Safety and effectiveness of ACTOS in pediatric patients have not been established.
ACTOS is not recommended for use in pediatric patients based on adverse effects
observed in adults, including fluid retention and congestive heart failure, fractures, and
urinary bladder tumors [see Warnings and Precautions (5.1, 5.4, 5.5 and 5.6)].
8.5 Geriatric Use
A total of 92 patients (15.2%) treated with ACTOS in the three pooled 16- to 26-week
double-blind, placebo-controlled, monotherapy trials were ≥65 years old and two
patients (0.3%) were ≥75 years old. In the two pooled 16- to 24-week add-on to
sulfonylurea trials, 201 patients (18.7%) treated with ACTOS were ≥65 years old and 19
(1.8%) were ≥75 years old. In the two pooled 16- to 24-week add-on to metformin trials,
155 patients (15.5%) treated with ACTOS were ≥65 years old and 19 (1.9%) were ≥75
years old. In the two pooled 16- to 24-week add-on to insulin trials, 272 patients (25.4%)
treated with ACTOS were ≥65 years old and 22 (2.1%) were ≥75 years old.
In PROactive, 1068 patients (41.0%) treated with ACTOS were ≥65 years old and 42
(1.6%) were ≥75 years old.
In pharmacokinetic studies with pioglitazone, no significant differences were observed in
pharmacokinetic parameters between elderly and younger patients [see Clinical
Pharmacology (12.3)].
Although clinical experiences have not identified differences in effectiveness and safety
between the elderly (≥65 years) and younger patients, these conclusions are limited by
small sample sizes for patients ≥75 years old.
Page 21 of 42
10
OVERDOSAGE
During controlled clinical trials, one case of overdose with ACTOS was reported. A male
patient took 120 mg per day for four days, then 180 mg per day for seven days. The
patient denied any clinical symptoms during this period.
In the event of overdosage, appropriate supportive treatment should be initiated
according to the patient’s clinical signs and symptoms.
11
DESCRIPTION
ACTOS tablets are a thiazolidinedione and an agonist for peroxisome proliferatoractivated receptor (PPAR) gamma that contains an oral antidiabetic medication:
pioglitazone.
Pioglitazone [(±)-5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2,4-]
thiazolidinedione monohydrochloride contains one asymmetric carbon, and the
compound is synthesized and used as the racemic mixture. The two enantiomers of
pioglitazone interconvert in vivo. No differences were found in the pharmacologic
activity between the two enantiomers. The structural formula is as shown:
C H3
S
N
O
O
O
NH
•
HCl
Pioglitazone hydrochloride is an odorless white crystalline powder that has a molecular
formula of C19H20N2O3S•HCl and a molecular weight of 392.90 daltons. It is soluble in
N,N-dimethylformamide, slightly soluble in anhydrous ethanol, very slightly soluble in
acetone and acetonitrile, practically insoluble in water, and insoluble in ether.
ACTOS is available as a tablet for oral administration containing 15 mg, 30 mg, or
45 mg of pioglitazone (as the base) formulated with the following excipients: lactose
monohydrate NF, hydroxypropylcellulose NF, carboxymethylcellulose calcium NF, and
magnesium stearate NF.
12
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
ACTOS is a thiazolidinedione that depends on the presence of insulin for its mechanism
of action. ACTOS decreases insulin resistance in the periphery and in the liver resulting
in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
Pioglitazone is not an insulin secretagogue. Pioglitazone is an agonist for peroxisome
proliferator-activated receptor-gamma (PPARγ). PPAR receptors are found in tissues
important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation
of PPARγ nuclear receptors modulates the transcription of a number of insulin
responsive genes involved in the control of glucose and lipid metabolism.
In animal models of diabetes, pioglitazone reduces the hyperglycemia,
hyperinsulinemia, and hypertriglyceridemia characteristic of insulin-resistant states such
as type 2 diabetes. The metabolic changes produced by pioglitazone result in increased
Page 22 of 42
responsiveness of insulin-dependent tissues and are observed in numerous animal
models of insulin resistance.
Because pioglitazone enhances the effects of circulating insulin (by decreasing insulin
resistance), it does not lower blood glucose in animal models that lack endogenous
insulin.
12.2
Pharmacodynamics
Clinical studies demonstrate that ACTOS improves insulin sensitivity in insulin-resistant
patients. ACTOS enhances cellular responsiveness to insulin, increases insulindependent glucose disposal and improves hepatic sensitivity to insulin. In patients with
type 2 diabetes, the decreased insulin resistance produced by ACTOS results in lower
plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c
values. In controlled clinical trials, ACTOS had an additive effect on glycemic control
when used in combination with a sulfonylurea, metformin, or insulin [see Clinical Studies
(14.2)].
Patients with lipid abnormalities were included in clinical trials with ACTOS. Overall,
patients treated with ACTOS had mean decreases in serum triglycerides, mean
increases in HDL cholesterol, and no consistent mean changes in LDL and total
cholesterol. There is no conclusive evidence of macrovascular benefit with ACTOS or
any other antidiabetic medication [see Warnings and Precautions (5.9) and Adverse
Reactions (6.1)].
In a 26-week, placebo-controlled, dose-ranging monotherapy study, mean serum
triglycerides decreased in the 15 mg, 30 mg, and 45 mg ACTOS dose groups compared
to a mean increase in the placebo group. Mean HDL cholesterol increased to a greater
extent in patients treated with ACTOS than in the placebo-treated patients. There were
no consistent differences for LDL and total cholesterol in patients treated with ACTOS
compared to placebo (see Table 14).
Table 14. Lipids in a 26-Week Placebo-Controlled Monotherapy Dose-Ranging Study
Triglycerides (mg/dL)
Baseline (mean)
Placebo
ACTOS
15 mg
Once
Daily
ACTOS
30 mg
Once
Daily
ACTOS
45 mg
Once
Daily
N=79
N=79
N=84
N=77
263
284
261
260
†
4.8%
-9.0%
HDL Cholesterol (mg/dL)
N=79
N=79
N=83
N=77
42
40
41
41
Percent change from baseline (adjusted mean*)
8.1%
14.1%
12.2%
19.1%
LDL Cholesterol (mg/dL)
N=65
N=63
N=74
N=62
139
132
136
127
4.8%
7.2%
5.2%
6.0%
Total Cholesterol (mg/dL)
N=79
N=79
N=84
N=77
Baseline (mean)
†
-9.3%
†
Baseline (mean)
-9.6%
†
†
Page 23 of 42
Baseline (mean)
225
220
223
214
4.4%
4.6%
3.3%
6.4%
*Adjusted for baseline, pooled center, and pooled center by treatment interaction
†p<0.05 versus placebo
In the two other monotherapy studies (16 weeks and 24 weeks) and in combination
therapy studies with sulfonylurea (16 weeks and 24 weeks), metformin (16 weeks and
24 weeks) or insulin (16 weeks and 24 weeks), the results were generally consistent
with the data above.
12.3 Pharmacokinetics
Following once-daily administration of ACTOS, steady-state serum concentrations of
both pioglitazone and its major active metabolites, M-III (keto derivative of pioglitazone)
and M-IV (hydroxyl derivative of pioglitazone), are achieved within seven days. At
steady-state, M-III and M-IV reach serum concentrations equal to or greater than that of
pioglitazone. At steady-state, in both healthy volunteers and patients with type 2
diabetes, pioglitazone comprises approximately 30% to 50% of the peak total
pioglitazone serum concentrations (pioglitazone plus active metabolites) and 20% to
25% of the total AUC.
Cmax, AUC, and trough serum concentrations (Cmin) for pioglitazone and M-III and M-IV,
increased proportionally with administered doses of 15 mg and 30 mg per day.
Absorption
Following oral administration of pioglitazone, Tmax of pioglitazone was within two hours.
Food delays the Tmax to three to four hours but does not alter the extent of absorption
(AUC).
Distribution
The mean apparent volume of distribution (Vd/F) of pioglitazone following single-dose
administration is 0.63 ± 0.41 (mean ± SD) L/kg of body weight. Pioglitazone is
extensively protein bound (>99%) in human serum, principally to serum albumin.
Pioglitazone also binds to other serum proteins, but with lower affinity. M-III and M-IV
are also extensively bound (>98%) to serum albumin.
Metabolism
Pioglitazone is extensively metabolized by hydroxylation and oxidation; the metabolites
also partly convert to glucuronide or sulfate conjugates. Metabolites M-III and M-IV are
the major circulating active metabolites in humans.
In vitro data demonstrate that multiple CYP isoforms are involved in the metabolism of
pioglitazone, which include CYP2C8 and, to a lesser degree, CYP3A4 with additional
contributions from a variety of other isoforms including the mainly extrahepatic CYP1A1.
In vivo study of pioglitazone in combination with gemfibrozil, a strong CYP2C8 inhibitor,
showed that pioglitazone is a CYP2C8 substrate [see Dosage and Administration (2.3)
and Drug Interactions (7)]. Urinary 6ß-hydroxycortisol/cortisol ratios measured in
patients treated with ACTOS showed that pioglitazone is not a strong CYP3A4 enzyme
inducer.
Page 24 of 42
Excretion and Elimination
Following oral administration, approximately 15% to 30% of the pioglitazone dose is
recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is
excreted primarily as metabolites and their conjugates. It is presumed that most of the
oral dose is excreted into the bile either unchanged or as metabolites and eliminated in
the feces.
The mean serum half-life (t1/2) of pioglitazone and its metabolites (M-III and M-IV) range
from three to seven hours and 16 to 24 hours, respectively. Pioglitazone has an
apparent clearance, CL/F, calculated to be five to seven L/hr.
Renal Impairment
The serum elimination half-life of pioglitazone, M-III, and M-IV remains unchanged in
patients with moderate (creatinine clearance [CLcr] 30 to 50 mL/min) and severe (CLcr
<30 mL/min) renal impairment when compared to subjects with normal renal function.
Therefore, no dose adjustment in patients with renal impairment is required.
Hepatic Impairment
Compared with healthy controls, subjects with impaired hepatic function (Child-TurcottePugh Grade B/C) have an approximate 45% reduction in pioglitazone and total
pioglitazone (pioglitazone, M-III, and M-IV) mean Cmax but no change in the mean AUC
values. Therefore, no dose adjustment in patients with hepatic impairment is required.
There are postmarketing reports of liver failure with ACTOS and clinical trials have
generally excluded patients with serum ALT >2.5 times the upper limit of the reference
range. Use caution in patients with liver disease [see Warnings and Precautions (5.3)].
Geriatric Patients
In healthy elderly subjects, Cmax of pioglitazone was not significantly different, but AUC
values were approximately 21% higher than those achieved in younger subjects. The
mean t1/2 of pioglitazone was also prolonged in elderly subjects (about ten hours) as
compared to younger subjects (about seven hours). These changes were not of a
magnitude that would be considered clinically relevant.
Pediatric Patients
Safety and efficacy of pioglitazone in pediatric patients have not been established.
ACTOS is not recommended for use in pediatric patients [see Use in Specific
Populations (8.4)].
Gender
The mean Cmax and AUC values of pioglitazone were increased 20% to 60% in women
compared to men. In controlled clinical trials, HbA1c decreases from baseline were
generally greater for females than for males (average mean difference in HbA1c 0.5%).
Because therapy should be individualized for each patient to achieve glycemic control,
no dose adjustment is recommended based on gender alone.
Ethnicity
Pharmacokinetic data among various ethnic groups are not available.
Page 25 of 42
Drug-Drug Interactions
Table 15. Effect of Pioglitazone Coadministration on Systemic Exposure of Other Drugs
Pioglitazone
Dosage
Regimen
*
(mg)
45 mg
(N = 12)
45 mg
(N = 12)
45 mg daily
for 21 days
(N = 35)
Coadministered Drug
Change
†
in Cmax
Change
†
in AUC
Name and Dose Regimens
‡
Warfarin
Daily loading then maintenance doses
based PT and INR values
Quick's Value = 35 ± 5%
Digoxin
R-Warfarin
↓3%
R-Warfarin
↓2%
S-Warfarin
↓1%
S-Warfarin
↑1%
0.200 mg twice daily (loading dose) then
0.250 mg daily (maintenance dose, 7 days)
Oral Contraceptive
[Ethinyl Estradiol (EE) 0.035 mg plus
Norethindrone (NE) 1 mg] for 21 days
↑15%
EE
NE
↑17%
↓11%
↑3%
EE
NE
↓13%
↓7%
45 mg
(N = 23)
Fexofenadine
60 mg twice daily for 7 days
↑30%
↑37%
45 mg
(N = 14)
Glipizide
5 mg daily for 7 days
↓3%
↓8%
↓3%
↓5%
↓26%
↓26%
↑1%
↓1%
↓13%
↓17%
↓14%
↓23%
↑2%
↑5%
45 mg daily
for 8 days
(N = 16)
Metformin
1000 mg single dose on Day 8
45 mg
(N = 21)
Midazolam
45 mg
(N = 24)
Ranitidine
45 mg daily
for 4 days
(N = 24)
7.5 mg single dose on Day 15
Nifedipine ER
45 mg
(N = 25)
Atorvastatin Ca
45 mg
(N = 22)
Theophylline
*Daily for 7 days unless otherwise noted
†% change (with/without coadministered drug and no change = 0%); symbols of ↑ and ↓ indicate the exposure
increase and decrease, respectively
‡Pioglitazone had no clinically significant effect on prothrombin time
Page 26 of 42
Table 16. Effect of Coadministered Drugs on Pioglitazone Systemic
Exposure
Coadministered Drug and
Dosage Regimen
Dose
Regimen
(mg)*
Pioglitazone
Change
†
in AUC
Change
†
in Cmax
Gemfibrozil 600 mg
twice daily for 2 days
(N = 12)
15 mg
single dose
↑3.2-fold
↑6%
Ketoconazole 200 mg
(N = 28)
45 mg
↑34%
↑14%
Rifampin 600 mg
daily for 5 days
(N = 10)
30 mg
single dose
↓54%
↓5%
Fexofenadine 60 mg
(N = 23)
45 mg
↑1%
0%
Ranitidine 150 mg
(N = 23)
45 mg
↓13%
↓16%
Nifedipine ER 30 mg
daily for 7 days
(N = 23)
45 mg
↑5%
↑4%
Atorvastatin Ca 80 mg
daily for 7 days
(N = 24)
45 mg
↓24%
↓31%
Theophylline 400 mg
(N = 22)
45 mg
↓4%
↓2%
‡
*Daily for 7 days unless otherwise noted
†Mean ratio (with/without coadministered drug and no change = 1-fold) % change
(with/without coadministered drug and no change = 0%); symbols of ↑ and ↓
indicate the exposure increase and decrease, respectively
‡The half-life of pioglitazone increased from 8.3 hours to 22.7 hours in the presence
of gemfibrozil [see Dosage and Administration (2.3) and Drug Interactions (7)]
Page 27 of 42
13
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
A two-year carcinogenicity study was conducted in male and female rats at oral doses
up to 63 mg/kg (approximately 14 times the maximum recommended human oral dose
of 45 mg based on mg/m2). Drug-induced tumors were not observed in any organ
except for the urinary bladder of male rats. Benign and/or malignant transitional cell
neoplasms were observed in male rats at 4 mg/kg/day and above (approximately equal
to the maximum recommended human oral dose based on mg/m2). Urinary calculi with
subsequent irritation and hyperplasia were postulated as the mechanism for bladder
tumors observed in male rats. A two-year mechanistic study in male rats utilizing dietary
acidification to reduce calculi formation was completed in 2009. Dietary acidification
decreased but did not abolish the hyperplastic changes in the bladder. The presence of
calculi exacerbated the hyperplastic response to pioglitazone but was not considered
the primary cause of the hyperplastic changes.
The relevance to humans of the bladder findings in the male rat cannot be excluded.
A two-year carcinogenicity study was also conducted in male and female mice at oral
doses up to 100 mg/kg/day (approximately 11 times the maximum recommended
human oral dose based on mg/m2). No drug-induced tumors were observed in any
organ.
Pioglitazone hydrochloride was not mutagenic in a battery of genetic toxicology studies,
including the Ames bacterial assay, a mammalian cell forward gene mutation assay
(CHO/HPRT and AS52/XPRT), an in vitro cytogenetics assay using CHL cells, an
unscheduled DNA synthesis assay, and an in vivo micronucleus assay.
No adverse effects upon fertility were observed in male and female rats at oral doses up
to 40 mg/kg pioglitazone hydrochloride daily prior to and throughout mating and
gestation (approximately nine times the maximum recommended human oral dose
based on mg/m2).
13.2 Animal Toxicology and/or Pharmacology
Heart enlargement has been observed in mice (100 mg/kg), rats (4 mg/kg and above)
and dogs (3 mg/kg) treated orally with pioglitazone hydrochloride (approximately 11, 1,
and 2 times the maximum recommended human oral dose for mice, rats, and dogs,
respectively, based on mg/m2). In a one-year rat study, drug-related early death due to
apparent heart dysfunction occurred at an oral dose of 160 mg/kg/day (approximately
35 times the maximum recommended human oral dose based on mg/m2). Heart
enlargement was seen in a 13-week study in monkeys at oral doses of 8.9 mg/kg and
above (approximately four times the maximum recommended human oral dose based
on mg/m2), but not in a 52-week study at oral doses up to 32 mg/kg (approximately 13
times the maximum recommended human oral dose based on mg/m2).
14
CLINICAL STUDIES
14.1 Monotherapy
Three randomized, double-blind, placebo-controlled trials with durations from 16 to 26
weeks were conducted to evaluate the use of ACTOS as monotherapy in patients with
Page 28 of 42
type 2 diabetes. These trials examined ACTOS at doses up to 45 mg or placebo once
daily in a total of 865 patients.
In a 26-week dose-ranging monotherapy trial, 408 patients with type 2 diabetes were
randomized to receive 7.5 mg, 15 mg, 30 mg, or 45 mg of ACTOS, or placebo once
daily. Therapy with any previous antidiabetic agent was discontinued eight weeks prior
to the double-blind period. Treatment with 15 mg, 30 mg, and 45 mg of ACTOS
produced statistically significant improvements in HbA1c and fasting plasma glucose
(FPG) at endpoint compared to placebo (see Figure 1, Table 17).
Figure 1 shows the time course for changes in HbA1c in this 26-week study.
Figure 1.
Mean Change from Baseline for HbA1c in a 26-Week Placebo-Controlled DoseRanging Study (Observed Values)
1.0
0.5
Mean
0.0
-0.5
-1.0
-1.5
-2.0
0
2
4
6
Placebo
10
14
Weeks
15 mg
30 mg
18
22
45 mg
26
Page 29 of 42
Table 17. Glycemic Parameters in a 26-Week Placebo-Controlled Dose-Ranging
Monotherapy Trial
Placebo
ACTOS
15 mg
Once
Daily
ACTOS
30 mg
Once
Daily
ACTOS
45 mg
Once
Daily
HbA1c (%)
N=79
N=79
N=85
N=76
Baseline (mean)
10.4
10.2
10.2
10.3
Change from baseline (adjusted mean*)
0.7
-0.3
-0.3
-0.9
†
†
Total Population
Fasting Plasma Glucose (mg/dL)
Baseline (mean)
Difference from placebo (adjusted mean*)
95% Confidence Interval
†
-1.0
(-1.6, -0.4)
-1.0
(-1.6, -0.4)
-1.6
(-2.2, -1.0)
N=79
N=79
N=84
N=77
268
267
269
276
9
-30
-32
-56
†
-39
(-63, -16)
†
-41
(-64, -18)
†
-65
(-89, -42)
†p≤0.05 vs. placebo
In a 24-week placebo-controlled monotherapy trial, 260 patients with type 2 diabetes
were randomized to one of two forced-titration ACTOS treatment groups or a mocktitration placebo group. Therapy with any previous antidiabetic agent was discontinued
six weeks prior to the double-blind period. In one ACTOS treatment group, patients
received an initial dose of 7.5 mg once daily. After four weeks, the dose was increased
to 15 mg once daily and after another four weeks, the dose was increased to 30 mg
once daily for the remainder of the trial (16 weeks). In the second ACTOS treatment
group, patients received an initial dose of 15 mg once daily and were titrated to 30 mg
once daily and 45 mg once daily in a similar manner. Treatment with ACTOS, as
described, produced statistically significant improvements in HbA1c and FPG at
endpoint compared to placebo (see Table 18).
Page 30 of 42
Table 18. Glycemic Parameters in a 24-Week Placebo-Controlled Forced-Titration
Monotherapy Trial
Placebo
ACTOS
30 mg*
Once Daily
ACTOS
45 mg*
Once Daily
HbA1c (%)
N=83
N=85
N=85
Baseline (mean)
10.8
10.3
10.8
0.9
-0.6
-0.6
Total Population
†
Change from baseline (adjusted mean )
†
‡
Baseline (mean)
†
Change from baseline (adjusted mean )
†
Difference from placebo (adjusted mean )
‡
-1.5
(-2.0, -1.0)
-1.5
(-2.0, -1.0)
N=78
N=82
N=85
279
268
281
18
-44
-50
Difference from placebo (adjusted mean )
‡
-62
(-82, -0.41)
‡
-68
(-88, -0.48)
*Final dose in forced titration
†Adjusted for baseline, pooled center, and pooled center by treatment interaction
‡p≤0.05 vs. placebo
In a 16-week monotherapy trial, 197 patients with type 2 diabetes were randomized to
treatment with 30 mg of ACTOS or placebo once daily. Therapy with any previous
antidiabetic agent was discontinued six weeks prior to the double-blind period.
Treatment with 30 mg of ACTOS produced statistically significant improvements in
HbA1c and FPG at endpoint compared to placebo (see Table 19).
Page 31 of 42
Table 19. Glycemic Parameters in a 16-Week Placebo-Controlled Monotherapy Trial
Placebo
ACTOS 30 mg
Once Daily
HbA1c (%)
N=93
N=100
Baseline (mean)
10.3
10.5
0.8
-0.6
Total Population
†
Baseline (mean)
-1.4
(-1.8, -0.9)
N=91
N=99
270
273
8
-50
†
-58
(-77, -38)
†p≤0.050 vs. placebo
14.2 Combination Therapy
Three 16-week, randomized, double-blind, placebo-controlled clinical trials were
conducted to evaluate the effects of ACTOS (15 mg and/or 30 mg) on glycemic control
in patients with type 2 diabetes who were inadequately controlled (HbA1c ≥8%) despite
current therapy with a sulfonylurea, metformin, or insulin. In addition, three 24-week
randomized, double-blind clinical trials were conducted to evaluate the effects of
ACTOS 30 mg vs. ACTOS 45 mg on glycemic control in patients with type 2 diabetes
who were inadequately controlled (HbA1c ≥8%) despite current therapy with a
sulfonylurea, metformin, or insulin. Previous diabetes treatment may have been
monotherapy or combination therapy.
Add-on to Sulfonylurea Trials
Two clinical trials were conducted with ACTOS in combination with a sulfonylurea. Both
studies included patients with type 2 diabetes on any dose of a sulfonylurea, either
alone or in combination with another antidiabetic agent. All other antidiabetic agents
were withdrawn at least three weeks prior to starting study treatment.
In the first study, 560 patients were randomized to receive 15 mg or 30 mg of ACTOS or
placebo once daily for 16 weeks in addition to their current sulfonylurea regimen.
Treatment with ACTOS as add-on to sulfonylurea produced statistically significant
improvements in HbA1c and FPG at endpoint compared to placebo add-on to
sulfonylurea (see Table 20).
Page 32 of 42
Table 20. Glycemic Parameters in a 16-Week Placebo-Controlled, Add-on to
Sulfonylurea Trial
Placebo
+ Sulfonylurea
ACTOS 15 mg
+ Sulfonylurea
ACTOS 30 mg
+ Sulfonylurea
N=181
N=176
N=182
Baseline (mean)
9.9
10.0
9.9
0.1
-0.8
-1.2
Total Population
HbA1c (%)
Difference from placebo + sulfonylurea
(adjusted mean*)
Baseline (mean)
Difference from placebo +sulfonylurea
(adjusted mean*)
†
†
-0.9
(-1.2, -0.6)
-1.3
(-1.6, -1.0)
N=182
N=179
N=186
236
247
239
6
-34
-52
†
-39
(-52, -27)
†
-58
(-70, -46)
†p≤0.05 vs. placebo + sulfonylurea
In the second trial, 702 patients were randomized to receive 30 mg or 45 mg of ACTOS
once daily for 24 weeks in addition to their current sulfonylurea regimen. The mean
reduction from baseline at Week 24 in HbA1c was 1.6% for the 30 mg dose and 1.7%
for the 45 mg dose (see Table 21). The mean reduction from baseline at Week 24 in
FPG was 52 mg/dL for the 30 mg dose and 56 mg/dL for the 45 mg dose.
The therapeutic effect of ACTOS in combination with sulfonylurea was observed in
patients regardless of the sulfonylurea dose.
Page 33 of 42
Table 21. Glycemic Parameters in a 24-Week Add-on to Sulfonylurea Trial
ACTOS 30 mg
+ Sulfonylurea
ACTOS 45 mg
+ Sulfonylurea
N=340
N=332
Baseline (mean)
9.8
9.9
-1.6
-1.7
Total Population
HbA1c (%)
Difference from 30 mg daily ACTOS
+ sulfonylurea (adjusted mean*) (95% CI)
-0.1
(-0.4, 0.1)
N=338
N=329
Baseline (mean)
214
217
-52
-56
+ sulfonylurea (adjusted mean*) (95% CI)
-5
(-12, 3)
95% CI = 95% confidence interval
Add-on to Metformin Trials
Two clinical trials were conducted with ACTOS in combination with metformin. Both
trials included patients with type 2 diabetes on any dose of metformin, either alone or in
combination with another antidiabetic agent. All other antidiabetic agents were
withdrawn at least three weeks prior to starting study treatment.
In the first trial, 328 patients were randomized to receive either 30 mg of ACTOS or
placebo once daily for 16 weeks in addition to their current metformin regimen.
Treatment with ACTOS as add-on to metformin produced statistically significant
improvements in HbA1c and FPG at endpoint compared to placebo add-on to metformin
(see Table 22).
Page 34 of 42
Table 22. Glycemic Parameters in a 16-Week Placebo-Controlled, Add-on to
Metformin Trial
Placebo
+ Metformin
ACTOS 30 mg
+ Metformin
N=153
N=161
Baseline (mean)
9.8
9.9
0.2
-0.6
Total Population
HbA1c (%)
†
-0.8
(-1.2, -0.5)
Difference from placebo + metformin (adjusted
mean*) 95% Confidence Interval
Baseline (mean)
Difference from placebo + metformin (adjusted
N=157
N=165
260
254
-5
-43
†
-38
(-49, -26)
†p≤0.05 vs. placebo + metformin
In the second trial, 827 patients were randomized to receive either 30 mg or 45 mg of
ACTOS once daily for 24 weeks in addition to their current metformin regimen. The
mean reduction from baseline at Week 24 in HbA1c was 0.8% for the 30 mg dose and
1.0% for the 45 mg dose (see Table 23). The mean reduction from baseline at Week 24
in FPG was 38 mg/dL for the 30 mg dose and 51 mg/dL for the 45 mg dose.
Page 35 of 42
Table 23. Glycemic Parameters in a 24-Week Add-on to Metformin Study
ACTOS 30 mg
+ Metformin
ACTOS 45 mg
+ Metformin
N=400
N=398
9.9
9.8
-0.8
-1.0
Total Population
HbA1c (%)
Baseline (mean)
+ Metformin (adjusted mean*) (95% CI)
-0.2
(-0.5, 0.1)
N=398
N=399
Baseline (mean)
233
232
-38
-51
+ Metformin (adjusted mean*) (95% CI)
†
-12
(-21, -4)
†p≤0.05 vs. 30 mg daily ACTOS + metformin
The therapeutic effect of ACTOS in combination with metformin was observed in
patients regardless of the metformin dose.
Add-on to Insulin Trials
Two clinical trials were conducted with ACTOS in combination with insulin. Both trials
included patients with type 2 diabetes on insulin, either alone or in combination with
another antidiabetic agent. All other antidiabetic agents were withdrawn prior to starting
study treatment. In the first trial, 566 patients were randomized to receive either 15 mg
or 30 mg of ACTOS or placebo once daily for 16 weeks in addition to their insulin
regimen. Treatment with ACTOS as add-on to insulin produced statistically significant
improvements in HbA1c and FPG at endpoint compared to placebo add-on to insulin
(see Table 24). The mean daily insulin dose at baseline in each treatment group was
approximately 70 units. The majority of patients (75% overall, 86% treated with placebo,
77% treated with ACTOS 15 mg, and 61% treated with ACTOS 30 mg) had no change
in their daily insulin dose from baseline to the final study visit. The mean change from
baseline in daily dose of insulin (including patients with no insulin dose modifications)
was -3 units in the patients treated with ACTOS 15 mg, -8 units in the patients treated
with ACTOS 30 mg, and -1 unit in patients treated with placebo.
Page 36 of 42
Table 24. Glycemic Parameters in a 16-Week Placebo-Controlled, Add-on to Insulin Trial
Placebo
+ Insulin
ACTOS 15 mg
+ Insulin
ACTOS 30 mg
+ Insulin
N=177
N=177
N=185
Baseline (mean)
9.8
9.8
9.8
-0.3
-1.0
-1.3
Total Population
HbA1c (%)
†
Baseline (mean)
Difference from placebo + Insulin (adjusted
†
-0.7
(-1.0, -0.5)
-1.0
(-1.3, -0.7)
N=179
N=183
N=184
221
222
229
1
-35
-48
Difference from placebo + Insulin (adjusted
†
-35
(-51, -19)
†
-49
(-65, -33)
†p≤0.05 vs. placebo + insulin
In the second trial, 690 patients receiving a median of 60 units per day of insulin were
randomized to receive either 30 mg or 45 mg of ACTOS once daily for 24 weeks in
addition to their current insulin regimen. The mean reduction from baseline at Week 24
in HbA1c was 1.2% for the 30 mg dose and 1.5% for the 45 mg dose. The mean
reduction from baseline at Week 24 in FPG was 32 mg/dL for the 30 mg dose and
46 mg/dL for the 45 mg dose (see Table 25). The mean daily insulin dose at baseline in
both treatment groups was approximately 70 units. The majority of patients (55%
overall, 58% treated with ACTOS 30 mg, and 52% treated with ACTOS 45 mg) had no
change in their daily insulin dose from baseline to the final study visit. The mean change
from baseline in daily dose of insulin (including patients with no insulin dose
modifications) was -5 units in the patients treated with ACTOS 30 mg and -8 units in the
patients treated with ACTOS 45 mg.
The therapeutic effect of ACTOS in combination with insulin was observed in patients
regardless of the insulin dose.
Page 37 of 42
Table 25. Glycemic Parameters in a 24-Week Add-on to Insulin Trial
ACTOS 30 mg
+ Insulin
ACTOS 45 mg
+ Insulin
N=328
N=328
Baseline (mean)
9.9
9.7
-1.2
-1.5
Total Population
HbA1c (%)
†
+ Insulin (adjusted mean*) (95% CI)
-0.3
(-0.5, -0.1)
N=325
N=327
Baseline (mean)
202
199
-32
-46
†
+ Insulin (adjusted mean*) (95% CI)
-14
(-25, -3)
†p≤0.05 vs. 30 mg daily ACTOS + insulin
16 HOW SUPPLIED/STORAGE AND HANDLING
ACTOS is available in 15 mg, 30 mg, and 45 mg tablets as follows:
15 mg tablet: White to off-white, round, convex, nonscored tablet with “ACTOS” on one
side, and “15” on the other, available in:
NDC 64764-151-04
NDC 64764-151-05
NDC 64764-151-06
Bottles of 30
Bottles of 90
Bottles of 500
30 mg tablet: White to off-white, round, flat, nonscored tablet with “ACTOS” on one side,
and “30” on the other, available in:
NDC 64764-301-14
NDC 64764-301-15
NDC 64764-301-16
Bottles of 30
Bottles of 90
Bottles of 500
45 mg tablet: White to off-white, round, flat, nonscored tablet with “ACTOS” on one side,
and “45” on the other, available in:
NDC 64764-451-24
NDC 64764-451-25
NDC 64764-451-26
Bottles of 30
Bottles of 90
Bottles of 500
Page 38 of 42
Storage
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled
Room Temperature]. Keep container tightly closed, and protect from light, moisture and
humidity.
17
PATIENT COUNSELING INFORMATION
See FDA-Approved Patient Labeling (Medication Guide).
•
•
•
•
•
•
•
It is important to instruct patients to adhere to dietary instructions and to have blood
glucose and glycosylated hemoglobin tested regularly. During periods of stress such
as fever, trauma, infection, or surgery, medication requirements may change and
patients should be reminded to seek medical advice promptly.
Patients who experience an unusually rapid increase in weight or edema or who
develop shortness of breath or other symptoms of heart failure while on ACTOS
should immediately report these symptoms to a physician.
Tell patients to promptly stop taking ACTOS and seek immediate medical advice if
there is unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or dark
urine as these symptoms may be due to hepatotoxicity.
Tell patients to promptly report any sign of macroscopic hematuria or other
symptoms such as dysuria or urinary urgency that develop or increase during
treatment as these may be due to bladder cancer.
Tell patients to take ACTOS once daily. ACTOS can be taken with or without meals.
If a dose is missed on one day, the dose should not be doubled the following day.
When using combination therapy with insulin or other antidiabetic medications, the
risks of hypoglycemia, its symptoms and treatment, and conditions that predispose
to its development should be explained to patients and their family members.
Inform patients that therapy with ACTOS, like other thiazolidinediones, may result in
ovulation in some premenopausal anovulatory women. As a result, these patients
may be at an increased risk for pregnancy while taking ACTOS. Therefore, adequate
contraception should be recommended for all premenopausal women who are
prescribed ACTOS.
Distributed by:
Takeda Pharmaceuticals America, Inc.
Deerfield, IL 60015
ACTOS is a trademark of Takeda Pharmaceutical Company Limited registered with the
U.S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals
America, Inc.
©1999 - 2013 Takeda Pharmaceuticals America, Inc.
ACT003 R20
Page 39 of 42
MEDICATION GUIDE
ACTOS (ak-TŌS)
(pioglitazone) tablets
Read this Medication Guide carefully before you start taking ACTOS and each time
you get a refill. There may be new information. This information does not take the
place of talking with your doctor about your medical condition or your treatment. If
you have any questions about ACTOS, ask your doctor or pharmacist.
What is the most important information I should know about ACTOS?
ACTOS can cause serious side effects, including new or worse heart failure.
• ACTOS can cause your body to keep extra fluid (fluid retention), which leads to
swelling (edema) and weight gain. Extra body fluid can make some heart
problems worse or lead to heart failure. Heart failure means your heart does not
pump blood well enough
• Do not take ACTOS if you have severe heart failure
• If you have heart failure with symptoms (such as shortness of breath or
swelling), even if these symptoms are not severe, ACTOS may not be right for
you
Call your doctor right away if you have any of the following:
• swelling or fluid retention, especially in the ankles or legs
• shortness of breath or trouble breathing, especially when you lie down
• an unusually fast increase in weight
• unusual tiredness
ACTOS can have other serious side effects. See “What are the possible side effects
of ACTOS?”
What is ACTOS?
ACTOS is a prescription medicine used with diet and exercise to improve blood
sugar (glucose) control in adults with type 2 diabetes. ACTOS is a diabetes
medicine called pioglitazone that may be taken alone or with other diabetes
medicines.
It is not known if ACTOS is safe and effective in children under the age of 18.
ACTOS is not recommended for use in children.
ACTOS is not for people with type 1 diabetes.
ACTOS is not for people with diabetic ketoacidosis (increased ketones in your blood
or urine).
Who should not take ACTOS?
See “What is the most important information I should know about ACTOS?”
Do not take ACTOS if you:
• have severe heart failure
• are allergic to any of the ingredients in ACTOS. See the end of this Medication
Guide for a complete list of ingredients in ACTOS
Page 40 of 42
Talk to your doctor before taking ACTOS if you have either of these conditions.
What should I tell my doctor before taking ACTOS?
Before you take ACTOS, tell your doctor if you:
• have heart failure
• have type 1 (“juvenile”) diabetes or had diabetic ketoacidosis
• have a type of diabetic eye disease that causes swelling in the back of
the eye (macular edema)
• have liver problems
• have or have had cancer of the bladder
• are pregnant or plan to become pregnant. It is not known if ACTOS will
harm your unborn baby. Talk to your doctor if you are pregnant or plan to
become pregnant about the best way to control your blood glucose levels while
pregnant
• are a premenopausal woman (before the “change of life”) who does not
have periods regularly or at all. ACTOS may increase your chance of
becoming pregnant. Talk to your doctor about birth control choices while taking
ACTOS. Tell your doctor right away if you become pregnant while taking ACTOS
• are breastfeeding or plan to breastfeed. It is not known if ACTOS passes
into your milk and if it can harm your baby. You should not take ACTOS if you
breastfeed your baby. Talk to your doctor about the best way to control your
blood glucose levels while breastfeeding
Tell your doctor about all the medicines you take including prescription and
over the counter medicines, vitamins, and herbal supplements.
ACTOS and some of your other medicines can affect each other. You may need to
have your dose of ACTOS or certain other medicines changed.
Know the medicines you take. Keep a list of your medicines and show it to your
doctor and pharmacist before you start a new medicine. They will tell you if it is
okay to take ACTOS with other medicines.
How should I take ACTOS?
• Take ACTOS exactly as your doctor tells you to take it
• Your doctor may change your dose of ACTOS. Do not change your ACTOS dose
unless your doctor tells you to
• ACTOS may be prescribed alone or with other diabetes medicines. This will
depend on how well your blood sugar is controlled
• Take ACTOS one time each day, with or without food
• If you miss a dose of ACTOS, take your next dose as prescribed unless your
doctor tells you differently. Do not take two doses at one time the next day
• If you take too much ACTOS, call your doctor or go to the nearest hospital
emergency room right away
• If your body is under stress such as from a fever, infection, accident, or surgery
the dose of your diabetes medicines may need to be changed. Call your doctor
right away
Page 41 of 42
•
•
•
•
Stay on your diet and exercise programs and test your blood sugar regularly
while taking ACTOS
Your doctor should do certain blood tests before you start and while you take
ACTOS
Your doctor should also do hemoglobin A1C testing to check how well your blood
sugar is controlled with ACTOS
Your doctor should check your eyes regularly while you take ACTOS
What are the possible side effects of ACTOS?
ACTOS may cause serious side effects including:
• See “What is the most important information I should know about
ACTOS?”
• low blood sugar (hypoglycemia). This can happen if you skip meals, if you
also use another medicine that lowers blood sugar, or if you have certain
medical problems. Lightheadedness, dizziness, shakiness, or hunger may
happen if your blood sugar is too low. Call your doctor if low blood sugar levels
are a problem for you
• liver problems. Call your doctor right away if you have:
o nausea or vomiting
o stomach pain
o unusual or unexplained tiredness
o loss of appetite
o dark urine
o yellowing of your skin or the whites of your eyes
• bladder cancer. There may be an increased chance of having bladder cancer
when you take ACTOS. You should not take ACTOS if you are receiving
treatment for bladder cancer. Tell your doctor right away if you have any of the
following symptoms of bladder cancer:
o blood or a red color in your urine
o an increased need to urinate
o pain while you urinate
• broken bones (fractures). Usually in the hand, upper arm, or foot in women.
Talk to your doctor for advice on how to keep your bones healthy.
• diabetic eye disease with swelling in the back of the eye (macular
edema). Tell your doctor right away if you have any changes in your vision.
Your doctor should check your eyes regularly
• release of an egg from an ovary in a woman (ovulation) leading to
pregnancy. Ovulation may happen when premenopausal women who do not
have regular monthly periods take ACTOS. This can increase your chance of
getting pregnant
The most common side effects of ACTOS include:
o cold-like symptoms (upper respiratory tract infection)
o headache
o sinus infection
Page 42 of 42
o muscle pain
o sore throat
Tell your doctor if you have any side effect that bothers you or that does not go
away. These are not all the side effects of ACTOS. For more information, ask your
doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects
to FDA at 1-800-FDA-1088.
How should I store ACTOS?
• Store ACTOS at 68°F to 77°F (20°C to 25°C). Keep ACTOS in the original
container and protect from light
• Keep the ACTOS bottle tightly closed and keep tablets dry
• Keep ACTOS and all medicines out of the reach of children
General information about the safe and effective use of ACTOS
Medicines are sometimes prescribed for purposes other than those listed in a
Medication Guide. Do not use ACTOS for a condition for which it was not prescribed.
Do not give ACTOS to other people, even if they have the same symptoms you
have. It may harm them.
This Medication Guide summarizes the most important information about ACTOS. If
you would like more information, talk with your doctor. You can ask your doctor or
pharmacist for information about ACTOS that is written for healthcare professionals.
For more information, go to www.actos.com or call 1-877-825-3327.
What are the ingredients in ACTOS?
Active Ingredient: pioglitazone
Inactive Ingredients: lactose monohydrate, hydroxypropylcellulose,
carboxymethylcellulose calcium, and magnesium stearate
This Medication Guide has been approved by the U.S. Food and Drug
Administration.
Distributed by:
Takeda Pharmaceuticals America, Inc.
Deerfield, IL 60015
Revised: November 2013
ACTOS is a trademark of Takeda Pharmaceutical Company Limited registered with
the U.S. Patent and Trademark Office and used under license by Takeda
Pharmaceuticals America, Inc.
©2009 - 2013 Takeda Pharmaceuticals America, Inc.
ACT003 R20
Medical Causation and
Epidemiologic Issues
Bruce R. Parker
Venable LLP
750 E Pratt St Ste 900
Baltimore, MD 21202
(410) 244-7534
[email protected]
Bruce R. Parker is a partner of Venable LLP in Baltimore, where his practice
focuses primarily on product liability and toxic tort litigation, in particular, pharmaceutical and medical device product liability litigation. Mr. Parker is a former member of the board of directors for both DRI and Lawyers for Civil Justice, and is a past
president of Maryland Defense Counsel, Inc., and the IADC.
Medical Causation and Epidemiologic Issues
Table of Contents
Presentation..............................................................................................................................................................121
Medical Causation and Epidemiologic Issues ■ Parker ■ 119
Presentation
Discovery Issues
Kimberly D. Baker
Williams Kastner PLLC
601 Union Street, Suite 4100
Seattle, WA 98101
(206) 628-6606
[email protected]
Kimberly D. Baker is an experienced trial lawyer who represents drug and medical
device companies in litigation, health care providers in litigation and regulatory
matters and defends other types of product liability claims. As a former nurse,
she has combined her clinical experience and knowledge from the ‘bedside’ to
analyzing issues of medical causation, working with expert witnesses and preparing
responses to damage claims. She is a frequent speaker and author of articles on
medical records, preparing corporate witnesses and embracing the differences in
communications and decisions making by men and women. Ms. Baker is a member
of the DRI Drug and Medical Device Steering Committee. She is a member of the
Federation of Defense and Corporate Counsel.
Discovery Issues
Table of Contents
I.Introduction................................................................................................................................................153
II. Why Is Discovery So Important?...............................................................................................................153
III. Standard Written Fact Discovery (Not In An MDL).................................................................................154
IV. MDL Discovery...........................................................................................................................................158
V.Depositions..................................................................................................................................................159
VI. Expert Discovery.........................................................................................................................................160
VII. When Things Don’t Go As Planned...........................................................................................................160
VIII. Litigation Hold............................................................................................................................................161
IX.Sanctions.....................................................................................................................................................165
Discovery Issues ■ Baker ■ 151
Discovery Issues
I.Introduction
Discovery is essential to litigation and a good discovery strategy is indispensable to the successful
defense of a drug or medical device products liability suit.
II. Why Is Discovery So Important?
a) Trial—the obvious answer is that what you don’t find out in discovery, you get surprised with at
trial.
b) Discovery allows the parties to clarify and narrow the issues. Many products liability lawsuits
include claims for defective design, implied and/or express warranties, and failure to warn. It
often ends up that the facts “at issue” relate solely to the failure to warn claim. In addition, the
relevant time period for discovery of documents will typically be defined by the dates of prescription and use of a drug or medical device; frequently, the relevant time period for discovery
of information relating to the drug or device can be limited to events occurring prior to and during the plaintiff ’s use. Discovery helps to get to what’s “at issue:”
c) Trial lawyers cast a wide net. Discovery gives each party with information about the real value of
their cases.
i) What does this have to do with discovery? Plaintiffs’ counsel in mass tort cases work in volume. They may bring a number of cases before evaluating the merits of them in a rush to
beat statutes of limitations or obtain plaintiffs. Many of these cases lack merit. Discovery
will help to weed those cases out.
ii) Discovery forces plaintiffs’ counsel to do work for their cases, and this may constitute the
first “hard look” at the viability of the cases.
d) Case evaluation: Discovery also gives the defense information about its case—the strengths and
weaknesses. Knowledge of the documents in your clients’ files is a key to evaluating the case,
identifying and working with witnesses, and shaping defense themes.
e) Summary judgment: Beyond the “big picture” information about the value of a case and the
strengths and weaknesses of the defense, discovery provides the information that supports
summary judgment motions. Federal courts—where many prescription drug/medical device
product liability suits end up—have a “liberal pleading standard:’ This means that few are dismissed at the pleading stage. Every piece of discovery—interrogatory answers, documents,
requests for admission, depositions, can yield valuable information for a summary judgment
motion. For example:
i) A prescriber may testify at his deposition that the labeling adequately warned him of the
side effect the plaintiff allegedly experienced. The plaintiff in a prescription drug product
liability case cannot prove proximate cause if the prescriber knew of the side effect and prescribed it anyway.
ii) Medical records obtained during discovery can make or break a case.
iii) Requests for admission can be valuable in “locking in” statements by plaintiff, providing
admissible evidence or confirming a lack of essential evidence for purposes of a dispositive
motion.
iv) FDA approvals or other actions upon labeling changes can be significant to a summary
judgment motion based upon federal preemption principles.
III. Standard Written Fact Discovery (Not In An MDL)
1) Introduction: Once initial pleadings have been filed, a discovery schedule is set, often by way of
a case management order. The implementation of a discovery schedule will depend on the court.
The scope and detail of a case management order can vary between state courts, but serious consideration should be given to negotiating a discovery schedule among the parties for presentation to the court, especially if the state court is known to be lax in administering deadlines. In
federal court, Rule 26( f) requires that the parties confer before any discovery proceeds (unless
ordered by the court or agreed to by the parties).
a) State court deadlines to consider:
i) a date for the close of written discovery;
ii) a deadline for depositions of fact witnesses (consider whether this should include
treating physicians, or whether a different deadline should apply to the latter witnesses);
iii) a deadline for the disclosure of experts, and any reports required by state practice
rules; it is strongly recommended that the disclosure be staggered between the witnesses’ with plaintiffs disclosing first;
iv) a deadline by which expert witnesses should be deposed; again, staggered deadlines
should be considered. Ideally, plaintiff ’s experts would be disclosed, reports provided,
and deposed before defendants have to disclose experts. In practice, these deadlines
can become squeezed and defense reports are frequently due before plaintiff ’s experts
are deposed.
b) Federal court: Local rules govern
i) Parties confer, agree to discovery plan (scheduling order);
ii) Scheduling order submitted—provides timing of discovery, dispositive motions, and
addresses issues related to privilege and/or the disclosure of electronically stored
information. The same considerations outlined for state court case management
orders apply here, if not governed by local rule.
2) Federal Rule 26(a), Initial disclosures
a) Information required by Rule 26(a)(1):
i) Names/addresses/telephone numbers of individuals likely to have discoverable information that will be used to support claims or defenses (unless solely for impeachment), and the subjects of information:
(1) I n products liability cases, the subject of the information will often include the
areas identified below in (b )(i);
(2) C
ompany employees should be contacted through you, not directly (provide
name, title, and “c/o” your address);
(3) Identify healthcare providers for the plaintiff (by name, if known).
ii) Copy of, or description by category and location of all documents, electronically
stored information, and tangible things in the possession of the party that may be
used to support claims or defenses, unless used solely for impeachment;
iii) Computation of damages (this is seldom applicable to the defendant, who typically
does not seek damages);
iv) Information about any insurance agreement which may satisfy part or all of a judgment or indemnify or reimburse for payments made to satisfy a judgment.
b) Rule 26( a) requires basic fact gathering with your client before filing Rule 26 disclosures.
Begin to piece together the company’s story, and the major players, before Rule 26 disclosures are due.
i) Interview individuals who know the story behind the drug or medical device, and
identify the documents that will be essential components of the defense and discovery—in a products liability suit this will often involve the following areas:
(1) R
egulatory affairs (IND/NDA, or in the case of a device, the PreMarket
Application(s) (PMA), the 510(k) submission(s), and post-marketing regulatory
files );
(2) Persons responsible for adverse event report processing/submission;
(3) Marketing (marketing and promotional materials during relevant time period);
(4) S ales (for example, identify the sales representatives who detailed the prescribing physician, and determine what materials they used and what “call notes” they
may have generated);
(5) S cientific/Clinical (individuals involved in the development, preclinical, and clinical testing of the drug).
ii) Consider that every individual you identify may be deposed. As you interview someone, think about what kind of witness he or she would make.
3) Interrogatories and Requests for Production:
a) Plaintiff ’s Interrogatories/RFPs to Defendants:
i) It is essential to think about privilege, privacy interests, and trade secrets at this stage:
(1) I n the case of a prescription drug or implantable device, the IND/NDA or PMA,
respectively, is often the first level of a response. These files contain trade secret
information, as well as information related to clinical trials that may raise privacy
issues (e.g. patient names).
(a) S tandard response might be: “Defendant will make responsive documents from
the IND/NDA available for inspection at a mutually convenient time upon
entry of and subject to an appropriate protective order covering all of the documents contained in the IND/NDA:’
(b) Work to get a protective order in effect.
(i) In Autotech Tech. Ltd P’ship v. Automationdirect.com, Inc., 237 F.R.D.
405 (N.D. Ill. 2006), aff ’d, 471 F.3d 745 (7th Cir. 2006), a general product
liability case, the court held that the defendant’s list of customers who had
been sold or solicited to purchase products were confidential trade secrets
and names could be redacted during discovery. The defendant’s motion for
protective order to redact customer information was granted.
(c) R
equests related to clinical trials raise privacy issues as well as trade secret/
proprietary information.
(d) Th
ere may be other regulatory submissions that form the first level of a
response, as well—for example, requests for or correspondence with FDA
regarding labeling changes, especially if the labeling change is significant to a
federal preemption defense.
(2) F ederal regulations prohibit releasing personal identifying information related to
adverse event reports.
(3) E
-discovery: E-discovery places significant, potentially onerous burdens on corporate clients, both in terms of cost and the time demanded of corporate employees. One of the most important considerations is which party will bear the costs
of the discovery method that is selected. This is a significant point for negotiation
and, if necessary, judicial oversight.
(4) R
eview documents being produced for privilege, trade secret, other proprietary
information.
(a) Document what is not being produced in a privilege log;
(b) Redactions: often, the privileged or confidential material in a document can
be redacted, permitting the production of a document that initially was determined not to be subject to discovery; however, redaction can be a burdensome
procedure.
(c) I n Coito v. Superior Court, 54 Cal. 4th 480 (2012), the court held that audio
recorded witness statements taken by investigators hired by the defendant were
entitled to qualified work product protection and may be entitled to absolute
protection if the disclosure would reflect “an attorney’s impressions, conclusions,
opinions, or legal research or theories.”
ii) Think about relevance and burdensomeness of the requests:
(1) P
laintiffs may not be entitled to know about every adverse event report; consider limiting initial production to those that are substantially related in type to
the injury alleged, and which precede the injury or incident at issue (the limitation is based on what would constitute adequate notice to the client of a potential
product issue and is related to the duty to warn).
(a) I n Brown v. Novartis Pharmaceuticals Corp., 2012 U.S. Dist. LEXIS 104985
(E.D.N.C. July 26, 2012), the court addressed whether adverse drug reports
(ADRs) are admissible at trial. To determine whether the ADRs were of probative
value, the court applied the “substantially similar” theory and held that the ADR
must be substantially similar to the matter before the court and the plaintiff ’s
condition to be admissible.
(2) Identify the relevant time period(s) for failure to warn claims, defect claims
(3) T
ypically, files must be produced in the manner in which they are maintained in
the regular course of business, OR a more targeted production can be made, in
which defense counsel selects the responsive documents and produces them in
response to individual requests.
iii) Examples
(1) I n Heraeus Kulzer, GmbH v. Biomet, Inc., 633 F.3d 591 (7th Cir. 2011), a foreign company sought discovery from a U.S. company under 28 U.S.C. 1782 in federal district court. The court acknowledged that the statute allows a foreign party
to make broad discovery requests, but held that courts must be alert for potential
abuses that would subject the U.S. party to unreasonable discovery requests and
increased expense.
b) Defendant’s Interrogatories/Requests For Production to Plaintiffs:
i) Information to obtain:
(1) Who?
(a) P
laintiff ’s essential information—employment history (authorization may be
needed), social security number, prior lawsuits, criminal history, sources of
income (social security authorization may be needed), medical history, family
medical history, insurance information;
(b) F act witnesses—who will plaintiff use at trial, who saw the plaintiff during the
relevant time period;
(c) P
hysicians: prescribing physicians, treating physicians, attending physicians
during hospitalization, family physicians.
(2) What?
(a) Injury alleged:
(i) documentation of injury/medical costs
(ii) did anyone tell plaintiff that injury was caused by drug/device?
(iii) allegations regarding continuing effects of injury
(A) In Offenback v. L.M. Bowman, Inc., 2011 U.S. Dist. LEXIS
66432 (M.D. Pa. June 22, 2011), the court held that the plaintiff ’s
Facebook and MySpace pages could contain discoverable information if the information was relevant to the plaintiff ’s claims that his
injuries limited his physical abilities.
(b) M
edical records (HIPAA authorization needed)—familiarize yourself with
local services or national vendors, as litigation warrants, for obtaining and analyzing medical records;
(c) I nformation about the drug/medical device:
(i) Packaging;
(ii) Product;
(iii) Labeling/package insert;
(iv) Patient information, if applicable;
(v) Successor liability issues.
(A) In the In Re: Darvocet, Darvon and Propoxyphene Products
Liability Litigation, the court dismissed the claims against Endo
Pharmaceuticals Holdings Inc. and Endo Pharmaceuticals Inc.
because the drugs at issue were made by Endo’s newly acquired
subsidiaries. Because the original entity still existed, the court held
there was no successor and thus no successor liability.
(B) In Pichon v. Asbestos, 52 So. 3d 240 (La.App. 4 Cir. 2010),
the court held that the manufacturer that purchased some of its
predecessor’s assets was not a continuation of its predecessor, and
thus not liable for the predecessor’s actions, because continuation
requires a complete asset purchase. The court also considered that
the predecessor was still a viable defendant at the time the suit was
filed.
(3) W
hen? Gather information needed to identify the relevant time period—when
the plaintiff first became aware of the injury; when the drug/device was used;
(4) How much? Breakdown of damages, including loss of income, medical bills, etc.
4) Other discovery tools:
a) Independent medical examinations;
b) Consider whether a request for preservation is needed (e.g. remaining medicine in bottle if
acute reaction is alleged).
c) For medical devices: consider whether inspection and/or testing of device will be undertaken by plaintiff ’s experts, and whether your client may wish to do so (there often are
good reasons not to do so, if plaintiff intends to test).
d) Requests for admission:
i) Use: May provide confirmation of a lack of evidence on a dispositive issue in a case
(“You have no evidence that you purchased the over-the-counter product manufactured by Defendant”);
ii) Example: Venue RFA in factor concentrate cases—useful to establish lack of connection to a jurisdiction (forum non conveniens or venue transfer).
iii) In Colony Ins. Co. v. Harold Kuehn, 2011 U.S. Dist. LEXIS 106884 (D. Nev. Sep. 20,
2011), the defendant denied certain requests for admission based on “not enough
information to admit or deny.” The court imposed a duty of reasonable inquiry on the
defendant to answer the plaintiff ’s requests. If the defendant could not admit or deny a
particular request, the court required the defendant to explain why it could not answer
and also to certify and describe the reasonably inquiry made to obtain the information.
IV. MDL Discovery
1) How is discovery in an MDL different?
a) Written discovery, depositions, and expert discovery are often governed by scheduling
order—the cases may be divided up into “phases:”
b) Documentary discovery may be much more extensive as to both time period and subject
matter deemed to be relevant, but is centralized, done only once rather than on multiple
occasions for multiple different cases in different jurisdictions.
c) Limitations placed on number of fact witness depositions, time for depositions
d) Plaintiff Fact Sheets
i)Plaintiff fact sheets can be inaccurate or incomplete. See, e.g., In re Yasmin and Yaz
(Drospirenone) Marketing, Sales Practices and Products Liability Litigation, 2011 U.S.
Dist. LEXIS 80639 (S.D. Ill. July 25, 2011).
e) Defendant Fact Sheets (rare)
f) The key: familiarize yourself with the court’s Pre-Trial orders.
V.Depositions
1) Plaintiff ’s depositions
a)Goals:
i) Identify additional fact witnesses and physicians
ii) Elicit helpful admissions for breach of express warranty claims, informed consent
iii) Clarify periods of use of drug or device, limit alleged adverse reactions associated
with the drug and/or continuing complaints of injury
iv) Find out if there are documents in the plaintiff ’s possession that are relevant to the
case—e.g. diaries.
2) The “friend” or family deposition (non-medical fact witness)
3) Physician depositions:
a) Identify who should be deposed
i) The prescriber’s deposition may be the single most important deposition you take.
ii)Goals:
(1) Establish that the plaintiff needed the drug/device that it was or was not prescribed for indications listed on label (see off-label use, below).
(2) Establish that physician was aware of the medical literature, kept up on information regarding the drug or device through reading of the literature, conversations
and meetings with colleagues, and was aware of the specific risk alleged through
these sources and his/her own clinical education, training and experience.
(3) Alternatively, in the appropriate case, establish that the physician does not review
or rely on the information contained within the package insert in making individual prescribing decisions—that, instead, he/she makes those decisions based
on his own clinical judgment, training, experience and expertise.
(4) Determine whether there are any issues with respect to client sales representative
contacts; if so, you will need to know which sales representatives were in contact
with the physician, and try to interview them before the physician is deposed so
that there are no surprises. This is especially true if the case involved an off-label
prescription. In that case, you will want to establish through the physician, if you
can, that physicians make decisions with respect to the prescription of drugs and
devices that are based on their own clinical judgment based on individual patient
needs.
b) An important note regarding scheduling depositions—figure out whether state law allows
you to contact the doctor for scheduling and/or other purposes.
c) Know the medical records cold. Outline, chronologize the events to keep them clear and
fresh in your mind.
d) If the testimony from the physician is good, consider asking questions that could later help
identify the physician as an expert—educational background, specialized experience, etc.
4) Other depositions: There may be other people with useful information. If the case involves,
for example, fetal exposure to a medication and the plaintiff claims that the child experiences
learning disabilities as a result of the exposure—depose the child’s teachers.
5)Client depositions: In Toyota Motor Corp. v. Superior Court, 197 Cal. App. 4th 1107 (2011),
the court ordered the trial court to vacate a motion to compel that would require a product
manufacturer to produce five Japanese employees for depositions in California. The court relied
on California’s Code of Civil Procedure, which provides that a nonresident witness cannot be
compelled to appear in California.
VI. Expert Discovery
1) Finding an expert: resources include other lawyers, local academic medical faculties, journal
articles in the relevant area of clinical medicine or science, client referrals from in-house science
and clinical experts
2) Disclosure of experts and expert opinions
a)
In Ingram v. Novartis Pharmaceuticals Corp., ___ F.R.D. ___, (W.D. Okla. Jun. 19, 2012),
the court granted a defense motion to compel expert witness disclosures where the disclosure contained vague language about the expert’s proposed testimony and did not meet the
requirements under Rule 26.
3) The expert report
a)
In Tokai Corp. v. Easton Enterprises, Inc., 632 F.3d 1358 (2011), after the plaintiff submitted
late expert reports, the court entered summary judgment against the plaintiff because it had
failed to justify why it did not comply with the court rules and principles of discovery.
4) Expert depositions
VII. When Things Don’t Go As Planned
1) Motions to compel
a) Meet and confer first
b) When needed (example, failure to produce medical authorization)
i) See Ingram v. Novartis Pharmaceuticals Corp., ___ F.R.D. ___, (W.D. Okla. Jun. 19,
2012), section IV(2)(a).
c) Responding to motions to compel: the need for documentation of resources used, sources
queried for responsive information; documentation of conversations, negotiations with
plaintiff ’s counsel
d) Pay attention to local rules on electronic filing of medical records. If, for example, you need
to attach a medical record to support your motion to compel (or a response to the plaintiffs’
motion to compel), confirm whether medical information needs to be redacted or filed
under seal.
VIII. Litigation Hold
I. What is a Litigation Hold?
a. Litigation hold is a stipulation requiring a company to preserve all data that may relate to a
legal action involving the organization.
II. What Triggers the Litigation Hold?
a. When a client reasonably anticipates litigation the duty to preserve documentation is
invoked.
b. The duty to preserve requires that a party identify, locate, and maintain information and
tangible evidence that is relevant to specific and identifiable litigation.
i. It is not a rule explicitly mentioned in the Federal Rules of Civil Procedure (“FRCP”),
instead it arises from common law.
ii. Preservation obligations may also be acknowledged and enforced because of statutes
or regulations that are deemed to apply under the circumstances at issue. See, e.g., 18
U.S.C. §1519 (Sarbanes-Oxley Act §802).
c. What is reasonable anticipation?
i.When a party should reasonably anticipate litigation is a fact specific inquiry.
1. Clear Examples of litigation being reasonably anticipated:
a. Receipt of a summons.
b. Receipt of a complaint.
c. Receipt of a subpoena.
d. Formal notice that the organization is a target of a governmental investigation.
2. Ambiguous Examples of litigation being reasonably anticipated:
a. Receipt of an insurance claim.
b. Receipt of an opposing party’s preservation notice letter.
c. Receipt of a demand letter.
d. Receipt of a cease and desist letter.
i. D
epending on the facts and the party’s business, these ambiguous
examples may not sufficiently give rise to the question about whether
there is a duty to preserve.
ii. When the situation is ambiguous, a variety of factors could be helpful in determining
if litigation can be reasonably anticipated:
1. The nature and specificity of the complaint or threat.
2. The party making the claim.
3. The business relationship between the accused and accusing parties.
4. Whether the threat is direct, implied, or inferred.
5. Whether the party making the claim is known to be aggressive or litigious.
6. Whether a party who could assert a claim is aware of the claim.
7. Whether the company has learned of similar claims.
8. The experience of the industry, and
9. R
eputable press and/or industry coverage of the issue either directly pertaining
to the client or of complaints brought against someone similarly situated in the
industry.
iii. Whether litigation can be reasonably anticipated should be based on a good faith
and reasonable interpretation of the facts and circumstances as they are known at the
time.
1. A
party that obtains new information, after the initial decision is made, should
reevaluate the situation as soon as practicable. See, e.g., Stevenson v. Union Pacific
RR Co., 354 F.3d 739 (8th Cir. 2004).
iv. Plaintiff ’s Duty
1. B
ecause the plaintiff controls the litigation, reasonable anticipation may occur long
before a lawsuit is filed. Seeking advice of counsel or even discussing a plan to initiate litigation can trigger the duty to preserve electronically stored information
and documents relevant to the impending litigation. Rimkus Consulting Group, Inc.
v. Cammarata, 688 F. Supp. 2d 598, 641 (S.D. Tex. 2010).
v. Defendant’s Duty
1. A
party’s duty to preserve evidence prior to litigation must be founded on more
than just “an equivocal statement of discontent.” Cache La Poudre Feeds, LLC v.
Land O’Lakes, Inc., 244 F.R.D. 614, 622 (D. Colo. 2007). Vague rumors of indefinite
threats do not trigger a duty to preserve.
III. Implementing the Litigation Hold
a. It is generally a best practice to put the litigation hold in writing.
1. Th
e language of the litigation hold is less important. The important factor is if the
organization has a means to comply with its legal obligations, to preserve relevant
information in the event of actual or reasonably anticipated litigation or investigation. Documenting those steps will also be helpful if the organization is called
upon to prove the reasonableness of the decision-making process.
2. I n Chin v. Port Auth. of N.Y. & N.J., 685 F.3d 135 (2d Cir. 2012), the court held a
party’s failure to implement a litigation hold should be one factor in the determination of whether discovery sanctions should be issued. This decision abrogated
Pension Comm. of the Univ. of Montreal Pension Plan v. Banc of Am. Sec., LLC, 685
F. Supp. 2d 456 (S.D.N.Y. 2010) which had held that failure to issue a written litigation hold constituted gross negligence.
b. How much documentation must be preserved?
i. A
fter an organization determines it has a duty to preserve, it should begin to identify information to be preserved.
ii. L itigation holds do not require every shred of paper, email, or electronic document
to be saved.
iii. H
owever, the scope of the litigation hold may depend on—
1. the cost to preserve and potentially restore information;
2. the number of individual custodians involved in the matter;
3. the type of information involved;
4. and whether the hold is on active data, historical data, or future data because
litigation involves future or ongoing business activities.
iv. The general rule is that a party must retain all relevant documents in existence at the time the duty to preserve attaches, and any relevant documents
created thereafter.
1. However, there is a growing recognition of a “proportionality principle.” This
principle essentially requires that the litigation hold policies be proportional to
the case, or potential case.
2. Litigation holds do not apply to inaccessible backup tapes which may continue
to be recycled. Zubalake v. UBS Warbug LLC, 220 F.R.D. 212, 218 (2003).
c. To whom does litigation hold apply?
i. M
anagement, legal, IT, records management personnel, and even consultants and
vendors should be trained on the organization’s litigation hold policies, practices,
ad their responsibilities.
ii. L itigation holds apply to all sources of information within the party’s possession,
control, and custody that are likely to contain unique, relevant information.
iii. L itigation holds apply to things organization has physical control over such as file
cabinets, emails on company servers, thumb drives, company laptops, company
phones and PDAs.
iv. L itigation holds apply to things organization has contractual control over such as
outsourced service providers, storage facilities operators, and application service
providers.
v. I f the information is held outside of the United States, you must also be mindful of
foreign discovery laws that could conflict with U.S. discovery laws.
d. Legal Counsel’s Role
i. T
raditional role is counsel must inform the client of its duty to preserve potentially
relevant documents in the client’s custody or control and of the possible consequences of failing to do so.
ii. O
ther decisions have held that counsel also owes an independent duty to actively
supervise a party’s compliance with the duty to preserve. Counsel may be required
to issue a litigation hold at the outset of litigation or when litigation is reasonably
anticipated.
e. Legal Hold Notice to Employees/Parties
ii. I f an employee or agent learns of the hold, is that knowledge imputed broadly to
organization as a whole?
1. The answer depends on the nature of the knowledge, the potential litigation, and
the agent.
2. General Rule: an agent’s knowledge is imputed to the corporation where the
agent is acting within the scope of his authority and where his knowledge
relates to matter within the scope of that authority.
ii. A
company’s litigation hold policy should also include information about how to
communicate and train individuals within the organization on how to follow the
policy.
1. E.g. creating an internal company hotline number to allow employees to ask
questions and express concerns about the litigation hold.
iii. O
rganization should promptly send out the litigation hold notice and regular
reminders. Effective litigation hold notices and reminders should—
1. describe the matter at issue,
2. provide specific examples of the types of information at issue,
3. identify potential sources of information,
4. inform recipients of their legal obligations to preserve information,
5. and include reference to the potential consequences to the individual and the
organization of noncompliance.
6. It should be in a form, which may include email, written hard copy or, in some
cases, oral notice, depending on the circumstances.
7. The notice should also inform recipients whom they should contact if they have
questions or need additional information.
8. Again, each case must be evaluated based on its own individual facts and a preservation notice adapted to conform to the facts and circumstances unique to
that case.
f. Monitoring the hold
i. O
rganizations should develop ways to regularly monitor a litigation hold to ensure
compliance.
ii. Th
is may be accomplished by—
1. Distributing periodic reminders of the litigation hold,
2. Requiring employee confirmations,
3. Issuing litigation hold update notices i.e. any changes in scope of the hold,
4. Issuing updates about the litigation itself.
a. It is not sufficient to notify all employees of the litigation hold and
expect that the party will then retain and produce all relevant information. However, not every employee will require hands-on supervision from
an attorney but attorney oversight of the process, including the ability to
review, sample, or spot-check the collection efforts is important.
g. Release of the Hold
i. Upon the termination of the matter, the litigation hold should include procedures for
how the preserved documentation should be released.
ii. Release procedures may include a process for conducting a custodian and data crosscheck so the organization can determine whether the information to be released is
subject to any other ongoing preservation obligations.
IX.Sanctions
a. While Rule 37(e) of the FRCP states that absent exceptional circumstances, a court may not
impose sanctions under these rules on a party for failing to provide electronically stored information lost as a result of the routine, good-faith operation of an electronic information systems,
in enforcing the duty to preserve through spoliation sanctions, courts primarily rely upon their
inherent powers.
b. Discovery sanctions can:
i. include orders which direct that certain facts be taken as established;
ii. prohibit the disobedient party from supporting or opposing certain claims or from introducing certain matters into evidence;
iii. strike pleadings in whole or in part; dismiss the action in whole or in part;
iv. render a default judgment against the disobedient party;
v. impose monetary fines on the lawyers and/or clients;
vi. give adverse jury instructions; or exclude evidence if the court later concludes relevant evidence was destroyed in bad faith.
1.Board of Regents of the University of Nebraska v. BASF Corp., 2007 WL 3342423 (D.
Neb., Nov. 5, 2007), the court recommended that plaintiff ’s counsel be required to
produce affidavits showing efforts to preserve electronic information going forward,
pay defendant’s attorney fees regarding sanctions motion, immediately impose a litigation hold on all electronic information of clients to prevent further destruction of
evidence, and halt further progress in the case until these sanctions had been met,
among other sanctions.
2.In VOOM HD Holdings LLC v. EchoStar Satellite L.L.C., 93 A.D.3d 33, 939 N.Y.S.2d
321(2012), the court found that sanctions for adverse inferences were proper when
the defendant purposely deleted emails months after the litigation began. The defendant had previously been criticized for its substandard retention policies in different
case. See Broccoli v. EchoStar Communications Corp., 229 F.R.D 506 (D. Md. 2005).
3.In Victor Stanley, Inc. v. Creative Pipe, Inc., 269 F.R.D. 497 (D. Md. 2010), the court
ordered that a default judgment be granted against the defendant on the plaintiff ’s
primary claim because the plaintiff had deleted electronically stored information
(ESI) after the lawsuit was filed, attempted to permanently erase deleted ESI, and
failed to preserve an external hard drive containing key information.
4.In Knickerbocker v. Corinthian Colls., 298 F.R.D. 670 (W.D. Wash. 2014), the court
awarded the plaintiffs’ costs and attorney fees incurred due to the defendant’s spoliation of evidence. The court also imposed a monetary fine against the defendant and
levied a fine on defendant’s counsel. The defendant had failed to implement a litigation hold and ultimately deleted emails that were material to the employee’s EEOC
claim.
5.In Realnetworks, Inc. v. DVD Copy Control Ass’n, 264 F.R.D. 517 (N.D. Cal. 2009),
the court imposed monetary sanctions, awarded the plaintiff reasonable attorneys’
fees, and drew an adverse inference because the defendant destroyed notebooks that
belonged to a project manager. The notebooks were believed to contain information
about programs that were implicated in license agreement dispute.
6.In Innis Arden Golf Club v. Pitney Bowes, Inc., 257 F.R.D. 334 (D. Conn. 2009), the
litigation involved a CERCLA action to recover cleanup costs, motions for sanctions
against a golf club for spoliation of evidence were granted and evidence was excluded
because club breached duty to preserve sampling evidence and associated data, there
was no reason offered why it was not feasible for soil samples to be stored in laboratory, and consequences of loss of evidence were significant.
7.In Swofford v. Eslinger, 671 F. Supp. 2d 1274 (M.D. Fla. 2009), the court imposed monetary sanctions on in-house counsel for failing to preserve evidence and also destroying evidence.
Potential Pitfalls of FRCP 30(b) (6) and
30(b) (1) in Drug & Device Litigation
N. Karen Deming
Troutman Sanders LLP
600 Peachtree Street, Suite 5200
Atlanta, GA 30308-2216
(404) 885-3124
[email protected]
N. Karen “Kay” Deming is a partner in the Atlanta office of Troutman Sanders LLP.
Ms. Deming has over 35 years of experience as a litigating attorney specializing in
the defense of complex product liability actions involving personal injury claims,
many of which concern specialized and technical areas of science and medicine.
Her practice has required the development of knowledge and fluency in medical,
epidemiological, and other scientific disciplines, as well as contacts with numerous
reputable experts in these scientific fields. Ms. Deming has served as national
counsel for one of the world’s largest pharmaceutical companies regarding various
of their products, and has also served on national trial teams for other of her
pharmaceutical clients. These cases have required special admission to practice in
various state and federal courts in jurisdictions outside Georgia, including Alabama,
California, Florida, Illinois, Kansas, Kentucky, Minnesota, Mississippi, Nebraska,
New Jersey, New York, Nevada, North Carolina, Tennessee, Texas, Virginia, and
West Virginia. Ms. Deming is a member of DRI, where she serves on the Drug
and Medical Device Steering Committee, a fellow in the American College of Trial
Lawyers, and has been recognized as a leading lawyer in litigation by Chambers
USA, as well as Best Lawyers in America. Ms. Deming has been named to Georgia
Trend magazine’s Legal Elite in personal injury (2004-2005, 2008-2011). She has also
been selected as a Super Lawyer in Civil Litigation by Law & Politics and Atlanta
Magazine (2004-2012); recognized in as a leading corporate counsel in Super
Lawyers Corporate Counsel Edition (2010); Selected as a Top 100 Georgia Super
Lawyer by Law & Politics and Atlanta Magazine (2010); selected as a Top 50 Female
Georgia Super Lawyer by Law & Politics and Atlanta Magazine. (2005-2006, 20092012).
The author wishes to thank LeeAnn McCurry, former partner at Troutman Sanders
LLP, and Lennon Haas, a Troutman Sanders associate for their contributions to this
paper.
Table of Contents
I. Requirements and Potential Pitfalls of the 30(b)(6) Deposition.............................................................171
A. Analysis of the 30(b)(6) Notice..........................................................................................................172
1. The 30(b)(6) Notice Must Designate the Proposed Areas of Inquiry With
Reasonable Particularity.............................................................................................................172
2. Limitations On the Designated Areas of Inquiry Pursuant To Rule 30(b)(6).........................172
B. Selecting and Preparing the Appropriate Corporate Representative...............................................175
1. Who Is the Appropriate Corporate Representative?..................................................................175
2. Preparing For the 30(6)(6) Deposition.......................................................................................176
C. The Slippery Slope—Protecting Work Product From Discovery While Adequately
Investigating and Preparing the 30(B)(6) Witness............................................................................178
1. Application of Rule 30(b)(6) To Documents Normally Protected By the
Attorney-Client and/or Work Product Privileges......................................................................179
2. Compilations of Non-Privileged Documents Selected By Corporate
Counsel For the Purpose of Preparing the 30(b)(6) Witness....................................................179
II. The 30(b)(1) Deponent...............................................................................................................................180
A. Putting FRCP 30(b)(1) In Context.....................................................................................................180
B. Deposition of A Top Executive Or “Apex” Depositions.....................................................................181
1. Authority For Limiting Apex Depositions.................................................................................181
2. Strategy For Limiting APEX Depositions...................................................................................183
III.Conclusion...................................................................................................................................................185
Endnotes....................................................................................................................................................................186
Potential Pitfalls of FRCP 30(b) (6) and 30(b) (1) in Drug & Device Litigation ■ Deming ■ 169
Rules 30(b)(6) and 30(b)(1) of the Federal Rules of Civil Procedure have long provided civil litigants
the ability to notice the deposition of a corporate defendant, partnership, association, or government agency,
as well as specific corporate witnesses. These rules are powerful discovery tools, which can be effectively utilized and can cripple a meritorious defense if counsel do not understand the very precarious position they
present to their clients.
Rule 30(b)(6) imposes an obligation upon such a party to investigate designated areas of inquiry and
to educate and proffer an appropriate representative whose testimony will thereafter bind that entity. Various
publications and positions urged in more than a few cases have sought to utilize this Rule as a means both to
foist the cost of discovery onto the business entity, more often than not the corporate defendant in the context
of products liability litigation, as well as to invade areas normally protected by the attorney-client privilege
and/or work product doctrine. Properly noticed and executed 30(b)(6) depositions can provide a plaintiff with
significant advantages, and at least one commentator has urged its use as the primary method of discovery,
replacing “... wasteful and inefficient preliminary interrogatories that plague most lawsuits” See Cymrot, Mark
A., “The Forgotten Rule”, Litigation, Vol. 18, No. 3, p. 6, 7 Spring 1993 (hereinafter referred to as “Cymrot”).
Mr. Cymrot posited that
Rule 30(b)(6) has the further advantage of cutting off many of the usual refuges for the weak or
trapped witness. “I do not know” and “I do not remember” are not adequate answers under Rule
30(b)(6).
Cymrot at 7.
The following discussion will seek to discuss the very precarious nature of Rule 30(b)(6) to the corporate defendant. The topics covered include (1) obligations of the corporation once a Rule 30(b)(6) deposition notice is filed; (2) measures necessary for adequate preparation of a Rule 30(b)(6) deponent and potential
dangers associated with preparing a corporate representative for a 30(b)(6) deposition; and (3) available measures to protect the corporation from abusive, overly broad and burdensome 30(b)(6) designations. Also, discussed is the use of Rule 30(b)(1) to seek depositions of specific corporate representatives, more specifically,
corporate officers often referred to as “apex” depositions and how to defend against such notices.
I. Requirements and Potential Pitfalls of the 30(b)(6) Deposition
Given the current litigation climate, counsel for a corporate party should anticipate and prepare
for a potential 30(b)(6) deposition from the inception of the lawsuit so as not to be caught short when the
deposition is ultimately sought. In anticipating such discovery, one must first be familiar with the specific
requirements of Rule 30(b)(6) as well as its limitations. Upon actually receiving a 30(b)(6) notice, counsel
for the corporate party should employ a three-step plan for addressing and meeting the Rule 30(b)(6) requisites: (1) analyze carefully the 30(b)(6) notice to ensure it complies with the requirements of Rule 30(b)
(6), is not overly broad or burdensome and is not being sought for an improper purpose; (2) after ensuring
the notice is proper, select, designate and prepare adequately the corporate designee; and (3) at all times
ensure that attorney-client and work product privileges are maintained and protected. Each step is discussed more fully.
A. Analysis of the 30(b)(6) Notice
1.The 30(b)(6) Notice Must Designate the Proposed Areas of Inquiry
With Reasonable Particularity
Rule 30(b)(6)1 imposes upon the examining party the duty of designating “the areas of inquiry with
reasonable particularity...” United States v. Taylor, 166 F.R.D. 356, 360 (M.D.N.C. 1996). Clearly, when a 30(b)(6)
notice fails to describe the subject matter of the proposed examination, it is defective. See Murphy v. Kmart Corp.,
255 F.R.D. 497, 506 (D.S.D 2009). Similarly, when a notice is so broad as to be practically “limitless,” a notice may
be quashed for insufficiently identifying the examination areas sought. See Gen. Foods Corp. v. Computer Election
Sys., Inc., 211 U.S.P.Q. 49 (S.D.N.Y. 1980) (where Rule 30(b)(6) subpoena required non-party to produce competent witnesses and pertinent documents in response to 143 questions, and to recall “every fact, conception,
intention, understanding, belief and sense impression,” with respect to various patents, court would quash deposition notice as “entirely too broad and burdensome”); Skladzien v. St. Francis Reg’l Med. Ctr., No. 95-1518-MLB,
1996 U.S. Dist. LEXIS 20621, at *2 (D. Kan. Dec. 19, 1996) (request that defendant provide testimony, pursuant to
30(b)(6) notice, regarding any statement of fact set forth in the amended complaint that had been denied by corporation, did not provide with reasonable particularity the matters on which examination was requested; plaintiff was required to list specifically all subject matters for which a 30(b)(6) designation was sought). Courts have
generally found Rule 30(b)(6) designations between these two extremes to be sufficiently particularized.2
Accordingly, upon receipt of a 30(b)(6) notice, counsel for a corporate party must consider whether
the designated areas of inquiry are sufficiently particularized. If the request is practically “limitless” or if, in
order to prepare the corporate witness to respond fully to one or more designations, the deponent’s counsel
would be required to “marshal all of its factual proof,” the notice arguably lacks sufficient particularity, thus
entitling the corporate deponent to the protection of a Rule 26 protective order. In re Indep. Serv. Orgs. Antitrust Litig., 168 F.R.D. 651, 654 (D. Kan. 1996) (quoting United States v. Dist. Council of N.Y.C., No. 90 Civ.
5722, 1992 U.S. Dist. LEXIS 12307 (S.D.N.Y. Aug. 18, 1992)); see also Reed v. Bennett, 193 F.R.D. 689, 692 (D.
Kan. 2000); Skladzien, 1996 U.S. Dist. LEXIS 20621, at *1 (notice calling for designation of witness to testify as
to “any statement of fact set forth in the Amended Complaint” denied by the defendant, did not identify with
reasonable particularity the proposed areas of inquiry).3
2.Limitations On the Designated Areas of Inquiry Pursuant To Rule 30(b)
(6)
Because Rule 30(b)(6) contains no express restriction on the scope of a proper corporate deposition,
some proponents have claimed that the areas of inquiry that may be designated in a 30(b)(6) notice are very
broad, “limited only by Rule 23(b)’s requirement that information be ‘reasonably calculated to lead to the discovery of admissible evidence.” Cymrot at 6. See also Massey at 87-88. However, there are limitations to just
how far Rule 30(b)(6) may be used.
a.Availability of Reasonable and Less Burdensome Means of Discovery
The limits that courts are willing to impose on the 30(b)(6) deposition will vary depending on the
particular jurisdiction. Indeed, it appears that courts will consider on a case-by-case basis whether a given
subject matter may be explored through a 30(b)(6) deposition, or is better suited to other discovery devices.
The analysis often will depend on how subtle or complex the evidentiary and legal bases underlying a party’s contentions are. See Taylor, 166 F.R.D. at 362 n. 7 (M.D.N.C. 1996); McCormick-Morgan, Inc. v. Teledyne
Indus., 134 F.R.D. 275, 287 (N.D. Cal. 1991), rev’d in part on other grounds, 765 F. Supp. 611 (N.D. Cal. 1991).
For example, in In re Independent Service Organizations, the plaintiff (CCS) served Xerox with a 30(b)(6)
notice requesting testimony about facts supporting numerous paragraphs in Xerox’s Answer and Counterclaim. Upon motion, the court granted Xerox a protective order, stating:
Although we have no quarrel with CCS’s contention that it has a right to discover the facts upon
which Xerox will rely for its defense and counterclaims, CCS’s attempt to discover those facts
through a Rule 30(b)(6) deposition is overbroad, inefficient, and unreasonable. It also implicates serious privilege concerns.... Even under the present-day liberal discovery rules, Xerox is
not required to have counsel “marshal all of its factual proof ” and prepare a witness to be able to
testify on a given defense or counterclaim. We find the reasoning of the court in United States v.
District Council of New York City, No. 90 Civ. 5722 (CSH), 1992 WL 208284, at *15 (S.D.N.Y. Aug.
18, 1992), particularly apropos:
“To provide the information defendants seek would in effect require the Government to marshal
all of its factual proof and then provide it to [the 30(b)(6) designate] so that she could respond to
what are essentially a form of contention interrogatories. Aside from any issues of privilege, this
would be highly inefficient and burdensome, rather than the most direct manner of securing relevant information....”
168 F.R.D. at 654; see also In re Enron Creditors’ Recovery, No. 01-16034, 2007 WL 2680427, at *3 (Bankr.
S.D.N.Y. Sept. 6, 2007) (finding contention interrogatories more appropriate than 30(b)(6) deposition for
inquiry into the defendants’ “conclusions, opinions, and legal theory”); In re Tex. E. Transmission Corp. PCB
Contamination Ins. Coverage Litig., MDL No. 764, 1990 U.S. Dist. LEXIS 2443, *7-8 (E.D. Pa. Mar. 6, 1990) (use
of interrogatories, rather than 30(b)(6) deposition, was more appropriate mechanism for inquiring into opinions and/ or contentions that relate to facts or the application of law to facts in the context of defendant’s affirmative defenses).
Conversely, however, in Resolution Trust Corp. v. Sands, the defendants served an exceedingly broad
30(b)(6) notice upon the RTC seeking testimony as to the various bases of the RTC’s claims.4 151 F.R.D. 616,
620 (N.D. Tex. 1993). The RTC sought a protective order, contending that the topics of inquiry were oppressive and that less burdensome means were available to defendants to obtain such information. The court
concluded, however, that because the designated topics sought only the “factual basis” for the RTC’s claims,
and would not mandate the production of expert testimony, the RTC would be required to designate a representative to provide testimony on the areas of testimony noticed by defendants. Id. at 620; see also Ierardi v.
Lorillard, Inc., No. 90-7049, 1991 U.S. Dist. LEXIS 11887, *7 - 8 (E.D. Pa. Aug. 23, 1991) (defendant would be
required to produce 30(b)(6) witness to testify as to whether and when it developed knowledge of harmful
effects of asbestos and whether it ever warned the public about such effects).
Accordingly, if faced with an exceedingly broad 30(b)(6) notice, counsel should (1) evaluate the specific subjects designated; (2) determine whether a 30(b)(6) deposition is the most appropriate device by which
to discover the requested information; and (3) contemplate for purposes of supporting a motion for protective order, more reasonable, less burdensome and equally efficient alternatives to the 30(b)(6) deposition
proposed.5 In appropriate cases, courts have ordered that a party utilize other means of discovery in lieu of a
30(b)(6) deposition. See In re Enron Creditors’ Recovery, 2007 WL 2680427, at *3; PCB Contamination Insurance Coverage Litigation, 1990 U.S. Dist. LEXIS 2443, at *8; Taylor, 166 F.R.D. at 363 n. 7 ; McCormick-Morgan,
Inc., 134 F.R.D. at 286. But see Ierardi, 1991 U.S. Dist. LEXIS 11887 .6
b.Rule 30(b)(6) Deposition Sought For Improper Purposes
When it appears that information sought pursuant to a 30(b)(6) deposition is duplicative or proffered
as a means of harassment, or when an adequate response would require expert testimony, protection under
Rule 26 may be available. See, e.g., Schwarzkopf Techs. Corp. v. Ingersoll Cutting Tool Co., 142 F.R.D. 420 (D.
Del. 1992); Gen. Foods Corp. v. Computer Election Sys., Inc., 211 U.S.P.Q. 49 (S.D.N.Y. 1980); Sands, 151 F.R.D.
at 620.
Counsel should scrutinize the designated areas of inquiry in light of discovery previously made to
determine if Rule 30(b)(6) is being used for any improper purpose, such as an attempt to discover counsel’s
trial and discovery strategies. For instance, in American National Red Cross v. Travelers Indemnity Co., the
court supported the defendant’s refusal to respond to certain questions during its 30(b)(6) deposition regarding the “facts and documents which [defendant] contends support its affirmative defenses.” 896 F. Supp. 8,
13 (D.D.C. 1995). Prior to the 30(b)(6) deposition, the parties had exchanged over 200,000 pages of documents, deposed dozens of witnesses and exchanged hundreds of interrogatories over the course of discovery.
Finding that the defendant’s counsel had “spent much of their time culling through hundreds of thousands of
pages of documents, transcripts, and interrogatory responses, in an effort to select and compile the facts and
documents relevant to each separate affirmative defense,” the court concluded that the deposition inquiries
“intruded upon protected work product; in effect, what [plaintiff] was requesting was insight into [defendant’s] defense plan.” Id. at 13-14.
Similarly, in Coleman v. General Electric Co., the plaintiff filed 30(b)(6) notices seeking information
regarding the defendant’s search efforts to find documents and information responsive to the plaintiff ’s discovery requests, as well as the designation of witnesses to testify about certain employment circumstances.
No. 94-cv-4740, 1995 U.S. Dist. LEXIS 8186, at *5-6 (E.D. Pa. June 8, 1995). In granting the defendant’s motion
for protective order, the court concluded that:
[t]he problem in this case is distinguishing between questions which go to a deponent’s knowledge of the facts, and those which seek the discovery of the theory of the defense or which
invade the privacy of the trial preparation process... [citation omitted]. Questions about in-house
counsel’s view of the case, facts which counsel considers significant, or any specific questions to
be asked about the investigation or search efforts to locate documents all fall under the category
of questions about “mental impressions.”
Id. See also EEOC v. Am. Int’l Grp, No. 93 Civ. 6390, 1994 U.S. Dist. LEXIS 9815, at *8 (S.D.N.Y. July 18, 1994)
(30(b)(6) deposition inquires regarding EEOC’ s view of the relevant facts “can only be designed to explore
the EEOC’s determinations of how it intends to order its proof,” denying defendant’s motion to compel); SEC
v. Morelli, 143 F.R.D. 42, 47 (S.D.N.Y. 1992) (where it was undisputed that “all relevant, non-privileged evidence” had been produced by plaintiff, defendant’s 30(b)(6) notice, seeking specific information regarding
inside information allegedly received and disseminated by defendant, could only have been for purpose of
ascertaining “how the SEC intends to marshall [sic] the facts, documents and testimony in its possession and
to discover the inferences that plaintiff believes properly can be drawn from the evidence it has accumulated,”
granting SEC’s motion for protective order); United States v. Pepper’s Steel & Alloys, Inc., 132 F.R.D. 695, 699
(S.D. Fla. 1990) (plaintiffs questions during 30(b)(6) deposition seeking defendant’s interpretation of Florida
law “falls squarely within the opinion work product doctrine... Revealing a party’s interpretation of law presents a real nonspeculative risk of revealing the thoughts of [defendant’s] counsel as well as the deponent”).
Hence, when the areas of inquiry designated in a 30(b)(6) notice seek discovery relating to (1) subtle
or complex evidentiary contentions that may be difficult for a layman to understand or articulate, (2) the legal
basis for a claim or defense, or (3) counsel’s trial strategy, an application for a protective order should be made
either to narrow the scope of the 30(b)(6) notice or to have the examining party seek such discovery through
other, more appropriate means such as contention interrogatories.
B. Selecting and Preparing the Appropriate Corporate Representative
1.Who Is the Appropriate Corporate Representative?
a.The Corporation Must Make A Good-Faith Effort To Designate
Individuals With Knowledge of the Matters Sought To Be Discovered
Once the scope of the 30(b)(6) deposition has been adequately defined, the corporation must designate a representative who “has the authority to speak on behalf of the corporation with respect to the areas
within the notice of deposition.” Estate of Thompson v. Kawasaki Heavy Indus., Inc., 291 F.R.D. 297, 303 (N.D.
Iowa 2013). In designating a representative for the 30(b)(6) deposition, the corporate deponent is not limited to producing a single representative to testify on its behalf. Phillips v. Mfrs. Hanover Trust Co., No. 92 Civ.
8527, 1994 U.S. Dist. LEXIS 3748, at *15-16 (S.D.N.Y. Mar. 29, 1994). Rather, it may designate “such number
of persons as will satisfy the request.” Taylor, 166 F.R.D. at 356.
Significantly, the party seeking the deposition cannot demand or specify that a particular officer,
director or employee of the corporate defendant be designated to testify pursuant to a 30(b)(6) notice.7 See,
e.g., Operative Plasterers’ & Cement Masons’ Int’l Ass’n v. Benjamin, 144 F.R.D. 87 (N.D. Ind. 1992). Rather, the
corporate defendant has the right to determine which employees will speak on its behalf. See Fed. R. Civ. P.
30(b)(6) (“The named organization must . . . designate one or more officers, directors, or managing agents . .
. to testify on its behalf.”); James C. Winton, Corporate Representative Depositions Revisited, 65 Baylor L. Rev.
938, 967 (2013).
This right of designation, however, does not appear to be unlimited. Rather, in making its designations, the corporation “must make a conscientious good-faith endeavor to designate the persons having knowledge of the matters sought by [the discovering party].” FDIC v. Butcher, 116 F.R.D. 196, 199 (E.D.
Tenn. 1986), aff ’d, 116 F.R.D. 203 (E.D. Tenn. 1987). Courts have therefore frowned upon corporate parties
who designate individuals having no independent familiarity with the topics on which they are proffered. For
instance, in Butcher, the FDIC designated certain individuals to provide testimony regarding claimed losses
for which it sought to hold defendants liable. Rather than designating the primary investigators, however, the
FDIC chose representatives who it conceded were not expected to be trial witnesses and who had not participated in the FDIC’s investigation of the defendants’ allegedly wrongful conduct. These individuals were
provided with certain materials to review relating to the investigation prior to being offered as 30(b)(6) representatives. The proposed representatives were not, however, provided with a “six-part memorandum:’ which
had been prepared by the primary investigators and which the district court had ruled was protected from
disclosure. Id.
The court concluded that the FDIC’s designation of these individuals was inadequate and ordered the
FDIC to “redesignate Rule 30(b)(6) witnesses to answer questions regarding the 13 areas described in defendants’
Amended Notice of Depositions.” Id. at 202. In ordering the redesignation, the court chastised the FDIC for
trying to “reinvent the wheel” by having examiners other than the ones who have already compiled the six-part memoranda look over the same work papers and related documents and testify
about them... [when] the simplest, most economical thing to do would be to provide the defendants with the factual statements in the six-part memoranda and offer the examiner whose name
appears on the six-part memorandum for discovery if there are questions which need to be
asked.
Id. at 201. See also Resolution Trust Corp. v. S. Union Co., 985 F.2d 196, 197-98 (5th Cir. 1993) (where RTC possessed documents clearly identifying Jones as having personal knowledge of the subject of the deposition and
failed to produce those documents or designate Jones until after it had designated other, less knowledgeable,
witnesses, RTC did not “make a meaningful effort to acquit its duty to designate an appropriate witness,” making award of fees and costs under Rule 37(d) appropriate).
b.The Corporation May Be Required To Designate Non-Employees As
30(b)(6) Witnesses
While a corporation clearly has the option of designating a former employee who consents to testify in
response to a 30(b)(6) notice, see Kiryas Joel Local Dev. Corp. v. Ins. Co. of N. Am., No. 90 Civ. 4970, 1991 U.S. Dist.
LEXIS 3407, at *6 (S.D.N.Y. Mar. 21, 1991), it also appears that courts have occasionally required that an individual other than a current corporate employee be designated and produced pursuant to a 30(b)(6) notice.
For instance, in Sierra Rutile Ltd. v. Katz, plaintiff sought to depose the corporate defendants through
a 30(b)(6) notice. No. 90 Civ. 4913, 1995 U.S. Dist. LEXIS 118 (S.D.N.Y. Jan. 11, 1995). The defendants, however, were dormant and inactive entities, having no current officers with knowledge of the transactions at
issue. In response to the plaintiff ’s motion, the court ordered under the circumstances of that litigation that a
director of a majority shareholder of one defendant’s parent company, be designated as the defendants’ managing agent for purposes of the 30(b)(6) deposition. Id. at *23. See also In the Matter of the Arbitration between
P.R. Mar. Shipping Auth. and Star Lines, Ltd., No. 79 Civ. 2659 (Slip Op.) (S.D.N.Y. June 10, 1980) (court
ordered that a former employee be designated as a “managing agent” for purposes of a 30(b)(6) notice where
the corporate deponent had no officers, directors, agents or employees). But see Lapenna, 110 F.R.D. at 23
(where corporate defendant identified retired employee as the person responsible for animal and laboratory
testing of Depo-Medrol, it was not required to produce him pursuant to Rule 30(b)(6)).
To the extent a former employee has specific, relevant knowledge, or is more knowledgeable in a
given area than any current employee, the corporation should consider whether it would be beneficial to have
that individual designated as a corporate representative (with the concomitant ability, and duty, to prepare
that individual to testify). Once proffered as a 30(b)(6) witness, however, the former employee’s testimony will
be binding on the corporation.
2.Preparing For the 30(6)(6) Deposition
a.The Corporation’s Duty To Gather Information “Reasonably
Available”
The designated corporate representatives must be prepared to testify “as to matters known or reasonably available to the organization.” Fed. R. Civ. P. 30(b)(6). Because the representative’s duty is to testify as to
the corporations knowledge, the corporation has the “duty to gather reasonably available information...create
a spokesperson and educate him or her in order to comply with the Rule 30(b)(6) subpoena.” Elbein at 368. A
Rule 30(b)(6) deposition is not limited to what a particular representative or the corporation knows at the time
of the notice; nor is it limited to “discovery of facts clearly known to the corporation which could not otherwise
be obtained.” Mitsui & Co. (U.S.A.). Inc. v. P. R. Water Res. Auth., 93 F.R.D. 62, 65 (D.P.R. 1981). Rather, it encompasses the information that is known to the corporate deponent “after due inquiry.” Id. at 66 (emphasis added).
See also Biax Corp. v. Nvidia Corp., No. 09-cv-01257, 2010 WL 4038728, at *3 (D. Col. Oct. 14, 2010).8
b.The Corporate Witness Must Be Prepared To Provide Complete and
Binding Answers To the Designated Areas of Inquiry
After the corporation has gathered “reasonably available” information responsive to the 30(b)(6)
notice, counsel must prepare the designated witnesses “so that they may give complete, knowledgeable and
binding answers on behalf of the corporation.” Marker v. Union Fidelity Life Ins. Co., 125 F.R.D. 121, 126
(M.D.N.C. 1989); see also Taylor, 166 F.R.D. at 360-61.
Some courts consider a party’s failure to prepare a corporate deponent properly for a 30(b)(6) deposition to be “tantamount to a failure to appear” rendering the corporation subject to sanctions under Rule 37(d).
Taylor, 166 F.R.D. at 362.9 See also Pioneer Drive, LLC v. Nissan Diesel Am., Inc., 262 F.R.D. 552, 559 (D. Mont.
2009) (holding that “[w]hile a physical body was present [at 30(b)(6) deposition], no person who satisfied the
legal requirements of Rule 30(b)(6) was produced”); Barron v. Caterpillar. Inc., 168 F.R.D. 175, 177 (E.D. Pa.
1996) (“[W]hen the corporate designee lacks knowledge over the pertinent subject matter, courts find that the
corporation has failed to make any appearance at the deposition.”).
But is a 30(b)(6) witness “unprepared” simply because he or she may not be able to respond to one or
more of the questions posed by the examining party? One commentator has concluded that the answer to this
question is an unequivocal yes. See Cymrot at 7 (duty to investigate and prepare corporate designee’s renders
“I do not know” and “I do not remember” inadequate answers under Rule 30(b)(6)). While not all courts have
imposed such an absolute rule, some cases suggest that “I do not know” or “I do not remember” may, in fact,
be an insufficient response under Rule 30(b)(6). For instance, in Marker v. Union Fidelity Life Insurance Co.,
the plaintiff noticed the defendant’s 30(b)(6) deposition and specifically designated that a person knowledgeable about “claims processing and claims records, and... general file keeping, storage and retrieval systems of
defendant” should be produced. 125 F.R.D. 121 (M.D.N.C. 1989). The corporate representative provided, however, was unable to respond to specific questions concerning the retrieval of computerized data. Id. at 123. The
court, granting the plaintiffs motion to compel additional 30(b)(6) testimony, stated:
Even if defendant in good faith thought that the claims director would satisfy the deposition
notice, it had a duty to substitute another person once the deficiency of its Rule 30(b)(6) designation became apparent. . . .
Id. at 126 (emphasis added). Other courts have similarly found a “duty to substitute” when a 30(b)(6) designee
is unable to respond fully to an examining party’s questions. See In re Air Crash Disaster at Detroit Metro. Airport, 130 F.R.D. 627, 631 (E.D. Mich. 1989) (finding that if designee was unable to “provide detailed testimony
regarding the flight schedule exhibit, then Northwest must produce an individual who is competent to discuss
the contents of the document.”); Dravo Corp. v. Liberty Mut. Ins. Co., 164 F.R.D. 70, 75 (D. Neb. 1995) (stating
that if corporate designee’s testimony is deficient, “corporation is obligated to provide a substitute”).10
c.Examination of Corporate Designees On Matters Other Than the
Topics For Which They Have Been Proffered Under 30(b)(6)
Courts have disagreed as to whether a 30(b)(6) designee can be examined on topics beyond those
listed in the deposition notice or for which he or she was proffered. In Falchenberg v. NY State Dep’t of Educ.,
the district court held that if a party opts to employ the procedures of Rule 30(b)(6) to depose a representative of a corporation, that party must confine the examination to the matters stated with reasonable particularity which are contained in the notice of deposition. 567 F.Supp. 2d 513, 521 (S.D.N.Y. 2008). Questions and
answers exceeding the scope of the 30(b) (6) notice will not bind the corporation, but are merely treated as the
answers of the individual deponent. If a Rule 30(b)(6) deponent does not know the answer to questions outside the scope of the matters described in the notice, “then that is the examining party’s problem.” Id. See also
Paparelli v. Prudential Ins. Co., 108 F.R.D. 727 (D. Mass. 1985).11
Many courts, however, have reached the opposite result. In King v. Pratt & Whitney, the district court
concluded that
Rule 30(b)(6) should not be read to confer some special privilege on a corporate deponent
responding to this type of notice. Clearly, Plaintiff could simply re-notice a deponent under the
regular notice provisions and ask him the same questions that were objected to. However, Plaintiff should not be forced to jump through that extra hoop absent some compelling reason.
161 F.R.D. 475, 476 (S.D. Fla. 1995), aff ’d, 213 F.3d 647 (11th Cir. 2000).
The King court therefore ruled that when an examining party asks questions outside of the topics described in the 30(b)(6) notice, “the general deposition rules govern, i.e. Rule 26(b)(1)), so that relevant
questions may be asked and no special protection is conferred...” and, to the extent the corporate representative lacks knowledge regarding topics beyond those designated in the notice, “then that is the examining
party’s problem.” Id. See also Barron, 168 F.R.D. at 178 (where plaintiffs questioned designated corporate representative on topics beyond those specified in their 30(b)(6) notice and complained that corporate representative’s deposition testimony was inadequate, on motion to compel, plaintiff would be allowed to conduct
additional written discovery, but could only seek information that was within the purview of the topics listed
in their 30(b)(6) notice).
C. The Slippery Slope—Protecting Work Product From Discovery While
Adequately Investigating and Preparing the 30(B)(6) Witness
Recognizing the corporate defendant’s duty to gather information and prepare the 30(b)(6) corporate designee, some plaintiffs’ counsel may seek to use Rule 30(b)(6) to discover the corporate defendant’s trial
strategy and work product. A zealous advocate may even seek to discover under the auspices of Rule 30(b)(6)
information otherwise shrouded by attorney-client privilege. As one commentator has noted:
if counsel chooses to educate the witness, she must by necessity risk revealing knowledge of
and strategy about the case. The spokesperson’s testimony will necessarily reflect what counsel
believes to be important. Counsel’s analysis of the importance of facts, however, has always been
considered privileged. The revelation is therefore an infringement of traditional work product
protection.
Elbein at 370. Without question, for the examining party, “nothing could be more useful (even if excluded at
trial) than the opposing counsel’s trial strategy.” Id. at 372. See Cymrot at 8.
Attorneys’ work product, of course, is normally not discoverable in the absence of a showing “that
the party seeking discovery has substantial need of the materials in the preparation of the party’s case and
that the party is unable without undue hardship to obtain the substantial equivalent of the materials by other
means.” Fed. R. Civ. P. 26(b)(3). This privilege can be undercut, however, when the examining party is permitted to discover the materials used in preparing the 30(b)(6) witness. Specifically, Federal Rule of Evidence 612
permits the discovery of preparatory materials if, prior to testifying, the “witness uses a writing to refresh his
memory for the purpose of testifying” and “the court in its discretion determines it is necessary in the interest of justice.”12 Because the purpose underlying Rule 612 is “to provide a basis for cross-examination of testimony suggested by the documents,” the examining party will often contend that it affords the absolute right
to discover documents reviewed by a 30(b)(6) witness in preparing to give testimony. Bank Hapoalim, B.M. v.
Am. Home Assurance Co., No. 92 Civ. 3561, 1994 U.S. Dist. LEXIS 4091, at *16 (S.D.N.Y. Apr. 6, 1994).
Courts, however, have recognized the obvious “potential for conflict [that] exists between Rule 612,
which favors disclosure of materials used to refresh a witness’ recollection, and the work-product privilege.”
Redvanly v. Nynex Corp., 152 F.R.D. 460, 470 (S.D.N.Y. 1993) (quoting In re Joint E. and S. Dist. Asbestos
Litig., 119 F.R.D. 4, 5 (E.D.N.Y & S.D.N.Y. 1988)). Hence, courts confronted by this conflict have often opted
to consider requests for discovery preparation materials “on a case-by-case basis by balancing the competing interests in the need for full disclosure and the need to protect the integrity of the adversary system protected by the work-product rule.”Id. First, in order for preparatory materials to be discovered, courts require
the requesting party to show that the documents “had an impact on the testimony” of the deponent. Bank
Hapoalim, 1994 U.S. Dist. LEXIS 4091, at *8-9. If so, the court:
should weigh (1) any attempt at improper use of the work product doctrine to exceed the limits
of preparation on the one hand and concealment on the other, (2) the degree to which the documents in question are composed of factual material rather than an attorney’s legal analysis, and
(3) whether the disclosure demand “constitutes a fishing expedition.”
Id.
1.Application of Rule 30(b)(6) To Documents Normally Protected By the
Attorney-Client and/or Work Product Privileges
One must keep in mind that if documents protected by the attorney-client privilege or work product
doctrine are used in preparing a 30(b)(6) witness for deposition, the privileges may be deemed waived, subjecting the privileged documents to discovery. See Reed v Advocate Health Care, No. 06 C 3337, 2008 WL
162760, *1 (N.D. Ill. 2008) (citing James Julian, Inc. v. Raytheon Co., 93 F.R.D. 138, 145 (D. Del. 1982)); Wheeling-Pittsburg Steel Corp. v. Underwriters Labs. Inc., 81 F.R.D. 8, 9 (N.D. Ill. 1978) (where documents protected
by attorney-client privilege were reviewed by deponent prior to deposition, privilege was waived); Bank
Hapoalim, 1994 U.S. Dist. LEXIS 4091, at *20-21 (attorney-client privilege waived as to documents reviewed
by deponent in preparing for his deposition). Courts have justified such discovery finding that,
it is disquieting to posit that a party’s lawyer may ‘aid’ a witness with items of work product and
then prevent totally the access that might reveal and counteract the effects of such assistance...
with the anticipation that these efforts should remain forever unknowable and undiscoverable.
Redvanly, 152 F.R.D. at 470 (quoting Berkey Photo, Inc. v. Eastman Kodak Co., 74 F.R.D. 613, 616 (S.D.N.Y
1977)). See also Wheeling-Pittsburg Steel Corp., 81 F.R.D. at 10.
Extreme care should therefore be taken when determining which, if any, documents should be
reviewed by the 30(b)(6) corporate designee. To the extent the witness reviews materials that have been withheld from production due to privilege, counsel should be prepared to produce those documents to the examining party. Even if the witness does not review privileged documents, however, counsel must ensure that the
witness is educated as to any relevant, non-privileged facts contained in such documents. See FDIC v. Butcher,
116 F.R.D. 196 (E.D. Tenn. 1986) (counsel, in preparing 30(b)(6) witness, refused to permit witness to review
privileged memoranda for fear its production would be required by Rule 612; but because factual contentions
contained in memoranda were clearly discoverable, court ordered FDIC to redesignate 30(b)(6) witnesses and
educate them as to all discoverable matters).
2.Compilations of Non-Privileged Documents Selected By Corporate
Counsel For the Purpose of Preparing the 30(b)(6) Witness
A closer question is presented when a witness is provided a selection of non-privileged documents
compiled by the attorney for the purpose of deposition preparation. Most courts agree that “the selection and
compilation of documents by counsel... in preparation for pretrial discovery falls within the highly-protected
category of opinion work product” Sporck v. Peil, 759 F.2d 312, 316 (3d Cir.) cert. denied, 474 U.S. 903 (1985).
See also In re Allen, 106 F.3d 582, 608 (4th Cir. 1997). Indeed, in cases “involving extensive document discov-
ery, the process of selection and distillation is often more critical than pure legal research.” James Julian, Inc.,
93 F.R.D. at 144. Some courts have concluded that
[p]roper application of Rule 612 should never implicate an attorney’s selection, in preparation
for a witness’ deposition, of a group of documents that he believes critical to a case. Instead,
identification of such documents under Rule 612 should only result from opposing counsel’s own
selection of relevant areas of questioning, and from the witness’ subsequent admission that his
answers to those specific areas of questioning were informed by documents he had reviewed.
In such a case, deposing counsel would discover the documents through his own wit, and not
through the wit of his adversary.
Sporck, 759 F.2d at 318-19 (emphasis added and footnote omitted). See also Omaha Pub. Power Dist. v. Foster
Wheeler Corp., 109 F.R.D. 615, 617 (D. Neb. 1986) (examining party may question witness as to which, if any,
documents informed his testimony).
II. The 30(b)(1) Deponent
A. Putting FRCP 30(b)(1) In Context
In addition to Rule 30(b)(6), plaintiffs may seek to depose corporations through specifically named
officers, directors or managing agents pursuant to Rule 30(b)(1).13 Bd. of Trs. of Leland Stanford Junior Univ.
v. Tyco Int’l, Ltd., 253 F.R.D. 524, 525 (C.D. Cal. 2008) (citing GTE Products Corp. v. Gee, 115 F.R.D. 67, 68 (D.
Mass. 1987)). “At such a deposition, the testimony is of the corporation and if the corporation is a party, the
testimony may be used at trial by an adverse party for any purpose.” Gee, 115 F.R.D. at 68. Significantly, in
contrast to Rule 30(b)(6), Rule 30(b)(1) does not require that the subject matter of the noticed deposition be
disclosed. Operative Plasterers’ & Cement Masons’ Int’l Ass’n v. Benjamin, 144 F.R.D. 87, 90 (N.D. Ind. 1992).
Although nothing in Rule 30(b)(1) specifically obligates a corporate party to produce its officers,
directors or managing agents pursuant to a deposition notice, where specifically named in the 30(b)(1) notice,
courts generally agree that an appearance subpoena is unnecessary to compel the attendance of such witnesses. Stone v. Morton Int’l. Inc., No 96-NC-006, 1997 U.S. Dist. LEXIS 2077, at *17 (D. Utah Feb. 24, 1997).
See also 9A Charles Allan Wright & Arthur R. Miller et al., Federal Practice & Procedure §2460 (3d ed. 2010)
(“A subpoena under Federal Rule 45 is unnecessary to take the deposition of a party or of an officer, director,
or managing agent of a party.”). However, a corporate employee or agent who does not qualify as an officer,
director or managing agent is not subject to deposition by notice; rather, the examining party must procure
his or her attendance by subpoena pursuant to Rule 45. United States v. Afram Lines (USA), Ltd., 159 F.R.D.
408, 413 (S.D.N.Y. 1994); Gee, 115 F.R.D. at 69. Nor is the testimony of subordinate corporate employees binding on the corporation. United States v. Taylor, 166 F.R.D. 356, 361 (M.D.N.C. 1996) (testimony by “mere corporate employee” is not considered that of the corporation).
Courts have struggled in determining whether a designated corporate employee is a “managing
agent” such that his or her testimony will be binding on the corporation. See Massey at 83-84. Generally, the
examining party has the burden of establishing the status of a designated corporate employee, and whether
an employee can be deemed a managing agent of the corporation is a “fact-sensitive” inquiry, “to be answered
pragmatically on an ad hoc basis.” Afram Lines, 159 F.R.D. at 413 (quoting 8 Wright & Miller §2103). Such an
inquiry is dependent upon several factors:
“1) whether the individual is invested with general powers allowing him to exercise judgment
and discretion in corporate matters; 2) whether the individual can be relied upon to give testi180 ■ Defending Drug and Medical Device Litigation: A Primer for Young Lawyers ■ September 2014
mony, at his employer’s request, in response to the demands of the examining party; 3) whether
any person or persons are employed by the corporate employer in positions of higher authority than the individual designated in the area regarding which the information is sought by the
examination; 4) the general responsibilities of the individual ‘respecting the matters involved in
the litigation, [citation omitted]; and 5) whether the individual can be expected to identify with
the interests of the corporation.”
Afram Lines, 159 F.R.D. at 413 (quoting Sugarhill Records Ltd. v. Motown Record Corp., 105 F.R.D. 166, 170
(S.D.N.Y. 1985)); see Terry v. Modern Woodmen of Am., 57 F.R.D. 141, 143 (W.D. Mo. 1972) (questioned on
other grounds) (where proposed deponent was in complete charge of the negotiation and sale of insurance
contracts at issue and had the duties and powers of an insurance supervisor, he was “managing agent” for
purposes of testimony regarding manner in which he obtained approval to sell insurance contracts to base
personnel); Tomingas v. Douglas Aircraft Co., 45 F.R.D. 94, 96-97 (S.D.N.Y. 1968) (where proposed deponents
were sent by defendant to assist in investigation of airplane crash, were the only employees of defendant to be
present at investigation, were in complete charge of identifying minute pieces of wreckage, and had an identity of interest with their employer, employees would be considered managing agents for purposes of giving
testimony regarding accident investigation). Although courts typically look to all factors, identification with
interests of the employer often predominates. See 8A Wright & Miller §2103 (2010).
Where an employee’s deposition is noticed, individually, and not on behalf of the corporation, the
employee’s “status with the corporation” is a proper area of inquiry, and if, during the course of the deposition,
sufficient evidence is produced to establish that the employee is a managing agent of his or her employer, then
that deposition testimony maybe used against the corporation as provided in Rule 32(a)(2), just as if the examining party had noticed the deposition of the corporation through that individual. See Gee, 115 F.R.D. at 69.
While protective orders prohibiting a deposition entirely are not favored, Conti v. Am. Axle and Mfg.,
Inc., 326 F. App’x 900, 908-09 (6th Cir. 2009) (citing Salter v. Upjohn Co., 593 F.2d 649, 651 (5th Cir. 1979)), at
least one court has concluded that it may be appropriate to require the examining party to invoke Rule 30(b)
(6) first, prior to deposing individual corporate representatives via 30(b)(1). See Stone v. Morton Int’l, Inc., 170
F.R.D. 498, 504 (D. Utah 1997) (precluding plaintiff from deposing defendant’s officer without first showing
compliance with Rule 30(b)(6) or other discovery methods and reasonable exhaustion of the relevant subject
matter through those means). Where the designated corporate employee has direct involvement or personal
knowledge relating to the litigation, however, it is unlikely that the examining party will be required to utilize Rule 30(b)(6) or any other discovery method prior to noticing his or her deposition. See Mercantum (U.S.)
Corp. v. Chilean Line. Inc., No. 90 Civ. 1103, 1991 U.S. Dist. LEXIS 10093 (S.D.N.Y. July 23, 1991).
B. Deposition of A Top Executive Or “Apex” Depositions
1.Authority For Limiting Apex Depositions
When a plaintiff notices the deposition of the defendant’s chief executive officer or other top executive, defense counsel is forced into an immediate strategic decision: is the case too insignificant or the noticed
deponent too far removed from the facts of the case for the deposition to proceed, or could the executive tell a
story beneficial to the defense that could discourage plaintiff ’s counsel and bring the case to a quicker conclusion? Important considerations in deciding whether to proceed with the deposition of a top executive include
the inability to prepare the executive properly due to his or her busy schedule, subjecting the executive to
potential harassment, and causing detriment to the client’s business by monopolizing the executive’s time.
In light of these considerations, in-house counsel may conclude that the inconvenience to the executive and
to the corporation outweighs any benefits that could be obtained from the deposition. Once that decision is
made, defense counsel is confronted with the issue of how to respond to the deposition notice or subpoena.
First, counsel for the corporation should always attempt to confer with opposing counsel regarding
a top executive’s deposition. It is possible that opposing counsel will agree to a less intrusive method of discovery, or agree to depose some lower-level employees prior to deposing the top executive. If, however, such
counsel will not agree, the corporation’s counsel will need to seek intervention of the court pursuant to Federal
Rule 26.
In Abarca v. Merck & Co., the court noted that “[v]irtually every court that has addressed deposition
notices directed at an official at the highest level or ‘apex’ of corporate management has observed that such
discovery creates a tremendous potential for abuse or harassment.” No. 1:07-cv-0388, 2009 U.S. Dist. LEXIS
71300, at *22 (E.D. Cal. July 31, 2009) (citations omitted) (emphasis added). Accordingly, “[w]hen a party
seeks the deposition of a high-level executive (a so-called “apex” deposition), the court may exercise its discretion under the federal rules to limit discovery.” Groupion, LLC v. Groupon, Inc., No. 11-0870 MEJ, 2012 U.S.
Dist. LEXIS 12684, at *5 (N.D. Cal. Feb. 2, 2012). See also Naylor Farms, Inc. v. Anadarko OGC Co., No. 11-cv01528, 2011 U.S. Dist. LEXIS 68940 (D. Colo. June 27, 2011) (“Under what has become known as the “apex
doctrine the Court may protect a high level corporate executive....”).
Federal Rule 26(b)( 1) establishes the framework for discovery and provides that “[p]arties may
obtain discovery regarding any non-privileged matter that is relevant to any party’s claim or defense....” The
breadth of Rule 26(b)(1) is narrowed by 26(b)(2), which states,
[o]n Motion or on its own, the Court must limit the frequency or extent of use of the discovery
otherwise allowed by these rules... if it determines that (i) the discovery sought is unreasonably
cumulative or duplicative, or can be obtained from some other source that is more convenient,
less burdensome or less expensive; (ii) the party seeking discovery has had ample time to obtain
the information by discovery in the action; or (iii) the burden or expense of the proposed discovery outweighs its likely benefit, considering... the importance of the proposed discovery in
resolving the issues.
The Advisory Committee’s Note states that “[t]he [1993] Revisions to 26(b)(2) [were] intended to
impose additional restrictions on the scope and extent of discovery.” Rule 26(b)(2) gives a court “greater discretion in structuring or limiting discovery and thus defendants have a greater chance of succeeding in opposing the deposition of a corporate executive officer” Richard W. Davis, “Difficult Task: Defending Defendant’s
President/CEO at Deposition or Trial” DRI Trial Techniques Seminar. The appropriate procedural mechanism for seeking the relief enumerated in 26(b)(2) is a protective order, which a court may enter when “justice requires to protect a party or person from annoyance, embarrassment, oppression, or undue burden or
expense.” Fed. R. Civ. P. 26(c).
The Michigan Court of Appeals recently described the “apex rule” as acting not to shield high ranking officers, but to sequence discovery and encourage using less burdensome methods. Alberto v. Toyota Motor
Corp., 289 Mich. App. 328 (2010). See also State ex rel. Mass. Mut. Life Ins. Co. v. Sanders, 724 S.E.2d 353 (W.
Va. 2012). This interpretation presents an alternative understanding of the protections provided by Rule 26(b)
(2), which narrows the scope of discovery, in that courts may begin to focus less reliably on “protect[ing] a
party or person from annoyance, embarrassment, oppression, or undue burden or expense” when entering or
denying protective orders for executives. Fed. R. Civ. P. 26(c).
Rather than seeking to unburden a corporate officer, the court’s language suggests that the key interest in denying an executive deposition is maintaining efficient discovery. As a strategy, counsel for the cor182 ■ Defending Drug and Medical Device Litigation: A Primer for Young Lawyers ■ September 2014
poration should consider characterizing opposition to an executive deposition as an attempt to streamline
the discovery process instead of as an attempt to limit the plaintiff ’s discovery. J. Richard Moore and Paul V.
Lagarde, Handling the Apex Deposition Request, FDCC Quarterly, Volume 57, Number 2, Winter 2007, 153.
Counsel should also avoid focusing the response on how important the executive is or how inconvenient a
deposition would be for the executive, as these details may not capture a judge’s sympathies. Id. at 158.
2.Strategy For Limiting APEX Depositions
Depending on the jurisdictions, four primary arguments exist for barring or limiting the scope of an
executive’s deposition:
• the executive’s lack of personal, unique or superior knowledge about the facts of the case;
• the availability of less intrusive or alternative discovery methods to obtain the same information;
• the duplicative nature of the executive’s testimony with discovery already obtained in the case;
and
• improper motives of the plaintiff for noticing the deposition.
Charles F. Press and Erika C. Collins, “How To Avoid, Control, Or Limit Depositions Of Top Executives.”
Defense Counsel Journal, Vol. 63, No. 2, p. 214 (April 1996).
a.Lack of Personal, Unique or Superior Knowledge
The most common ground for limiting or barring a deposition is that the executive lacks any personal knowledge about the facts of the case. See Lewelling v. Farmers Ins. of Columbus, Inc., 879 F.2d 212,
218 (6th Cir. 1989) (upholding district court’s grant of protective order to bar plaintiff from deposing defendant’s chief executive officer who lacked knowledge of any relevant facts); Conti, 326 F. App’x at 905 (reversing
grant of protective order because record demonstrated CEO had personal knowledge of discoverable matters); Thomas v. IBM, 48 F.3d 478, 482 (10th Cir. 1995) (upholding district court’s grant of protective order on
grounds that, inter alia, defendant’s president submitted an affidavit that he lacked personal knowledge of the
facts of plaintiff ’s case). The executive’s lack of knowledge should be demonstrated to the court with an affidavit from the executive. Colonial Capital Co. v. Gen. Motors Corp., 29 F.R.D. 514, 518 (D. Conn. 1961).14
In some jurisdictions, courts require not only that an executive have personal knowledge regarding
circumstances for which he or she is being deposed, but also that the executive’s knowledge be superior to,
or unique from, that of more accessible potential deponents. Reif v. CNA, 248 F.R.D. 448, 451 (E.D. Pa.2008)
(recognizing and accepting other courts’ rulings disallowing depositions of “corporate executives because the
executives lacked superior or unique personal knowledge”); Baine v. Gen. Motors Corp., 141 F.R.D. 332 (M.D.
Ala. 1991).
Specifically, the court in Baine noted:
When a party seeks to depose high-level decisionmakers who are removed from the daily subjects of the litigation, the party must first demonstrate that the would-be deponent has unique
personal knowledge of the matter in issue. Moreover, the unique personal knowledge must be
truly unique, a deposition may not be allowed where the information could be had through
interrogatories, deposition of a designated spokesperson, or deposition testimony of other persons.
141 F.R.D. at 334 (finding that plaintiffs had not demonstrated the executive’s “superior or unique personal
knowledge”). See also, Apple Inc. v. Samsung Elecs. Co., 282 F.R.D. 259 (N.D. Cal. 2012) (either denying or
severely limiting the depositions of several major executives, finding that courts consider whether the depoPotential Pitfalls of FRCP 30(b) (6) and 30(b) (1) in Drug & Device Litigation ■ Deming ■ 183
nent has unique first-hand, non-repetitive knowledge of the facts at issue in the case and whether parties have
exhausted other less intrusive discovery methods); Guzman v. News Corp., No. 09 Civ. 9323, 2012 U.S. Dist.
LEXIS 91031 (S.D.N.Y. June 29, 2012) (finding that an executive, even as a direct supervisor, does not necessarily have “unique knowledge” and should therefore not be deposed). But see Conti, 326 F. App’x at 905 (finding that an executive could be deposed because he had personal knowledge, with no discussion of whether
there were other, non-executive, potential deponents with the information); Carr v. Double T Diner, 272 F.R.D.
431 (D. Md. 2010) (allowing an executive deposition because the executive “may have relevant knowledge”
with no consideration of whether the knowledge is unique or superior to that of other potential deponents).
b.Public Statements
When particular, potential litigation is anticipated, the corporate client must anticipate the likelihood
in today’s climate that an “APEX” deposition will be sought. Thus, it must weigh carefully the pros and cons of
an APEX witness making public statements about the subject matter of the litigation as such statements can
be used to rebut any argument that such witness has no personal or unique knowledge about the subject matter of the litigation.
While many courts recognize that being the public face of a corporation requires making statements
that may not be representative of an executive’s personal knowledge, other courts have used an executive’s public
statements to support a deposition request. In Doble v. Mega Life & Health Ins. Co., the court found that an executive’s public statements were part of his job as the public face of the company, and did not represent personal participation in relevant events. No. C 09-1611 CRB, 2010 U.S. Dist. LEXIS 56190 (N.D. Cal. May 18, 2010). See also
Naylor Farms, Inc. v. Anadarko OGC Co., No. 11-cv-01528, 2011 WL 2535067, at *4 (D. Col. June 27, 2011). Additionally, the Doble court rejected the argument that the executive’s ceremonial signature on certain documents
and generalized motivational admonitions were representative of any unique knowledge. Id. at *5.
Alternatively, granting a motion to compel an executive deposition, the court in In re TVA Ash Spill
Cases found that an executive’s public statements could be used as evidence of his specialized knowledge in
determining whether a deposition was appropriate. 2010 WL 2757176, at *1 (E.D. Tenn. July 13, 2010). The
court found that the executive’s testimony to a congressional committee on the plant ash disaster at issue,
along with a declaration admitting generalized knowledge of TVA operations, were sufficient evidence to
allow the executive to be deposed. Id. Executives regularly make public statements regarding their organizations, but they should remain guarded with respect to the content of those statements because plaintiffs’
attorneys may seek to argue that an executive’s public statements are evidence of the executive’s personal
knowledge, thereby making the executive available for deposition.
c.Alternatives to APEX Depositions
While lack of personal knowledge, as well as the other above-enumerated grounds are viable bases
for opposing the deposition of a top executive, “[i]t is very unusual for a court to prohibit the taking of a deposition altogether and absent extraordinary circumstances, such an order would likely be in error.” Salter v.
Upjohn, 593 F.2d 649, 651 (5th Cir. 1979). Thus, corporate counsel should always present the court with alternatives to prohibiting entirely a requested deposition. Reasonable alternatives may include an order that the
executive first be served written interrogatories to determine if the information can be provided in written
form. Coleman v. Gen. Elec. Co., No. 94-cv-4740, 1995 U.S. Dist. LEXIS 8186, *9 (E.D. Pa. June 8, 1995). The
court can also require that the plaintiff depose lower level executives or other employees to determine if the
same information is available without deposing the top executive. The court can always control the schedule of depositions, and can require plaintiff to take other depositions of persons with knowledge before the
executive. Salter, 593 F.2d at 650. If the deposition is to occur, the court can limit the length of the deposition.
Dynapower Sys. Corp. v. Ross, 1966 WL 86614 (S.D.N.Y. Oct. 31, 1966). The court can also limit the subject
matter and the areas of inquiry. Tri-Star Pictures, Inc. v. Unger, No. 88 Civ. 9129, 1997 U.S. Dist. LEXIS 2458, at
*25 (S.D.N.Y. Mar. 6, 1997) (citing Werthheim Schroder & Co., Inc. v. Avon Prods. Inc., 91 Civ. 2287, 1995 U.S.
Dist. LEXIS 79, (S.D.N.Y. Jan. 9, 1995)).
It is incumbent upon counsel opposing the deposition to develop a defense strategy reasonably calculated to protect the interests of the executive and the corporation while recognizing that the party seeking the
deposition is probably entitled to the discovery in some form. If a good faith conference with plaintiff ’s counsel affords no relief, counsel should apply for a protective order with a motion that sets forth reasonable alternatives to the requested discovery.
III.Conclusion
In the absence of proper preparation and precautions, the 30(b)(6) deposition presents a potential,
significant hazard for a corporation. Deposing parties often attempt to shift the cost of discovery to a corporation by noticing a 30(b)(6) deposition, designating areas of inquiry covering all aspects of the litigation, in
an attempt to force the corporation to investigate both the claims and defenses in the action, and to report the
results of such investigation in the course of the corporation’s deposition. The answers provided by the corporate designees will be binding on the corporation. Therefore, counsel for the corporate party must be able to
identify these tactics and take appropriate action in order to prepare and defend a 30(b)(6) deposition properly. Counsel must also be cognizant of obligations to investigate the designated areas of inquiry and to educate the corporate designee to testify as to these subjects. This process should begin well before a 30(b)(6)
notice is received. Indeed, from the very beginning of any litigation involving a corporation, counsel should
begin the tasks of (1) investigating the claims and defenses, not just from current employees, but from all
sources that might be considered “reasonably available” and (2) identifying corporate employees with relevant
knowledge who may be utilized as a 30(b)(6) witness. In complex cases, preparation of corporate witnesses
likely should begin before the notice of deposition is received.
Upon receipt of a 30(b)(6) notice, counsel must make a determination as to whether a protective
order should be sought. In the absence of a protective order, a corporate designee is obligated to respond to
questions on the areas of inquiry for which he or she is proffered. Where the designated areas of inquiry lack
sufficient particularity, would require counsel to “marshal all of its factual proof ” in order to prepare a witness
adequately to testify, or seeks discovery that is either improper or is better suited for other discovery devices,
counsel must seek a protective order.
Finally, counsel must be cognizant that, once the process of investigation and witness preparation
has begun, he or she is teetering on a “slippery slope” that may allow discovery of one’s work product. Hence,
in preparing and educating a corporate witness, as required by Rule 30(b)(6), counsel must be vigilant in protecting otherwise privileged information.
As to attempts to depose “APEX” corporate witnesses, resisting such depositions will likely be more
successful if the motion is characterized as an effort to streamline discovery instead of as a way to prevent an
executive from being inconvenienced. Executives should make public statements with caution to avoid creating the impression that they possess unique personal knowledge, which would open them up to deposition.
Affidavits attesting to lack of knowledge should explicitly and unequivocally state that the executive lacks
knowledge, otherwise they may be deemed insufficient. Finally, corporate counsel should emphasize that the
knowledge requirement to depose an executive is more than simply “personal knowledge but is “superior or
unique knowledge;”
BIBLIOGRAPHY
(not necessarily definitive)
In preparing this paper, the author has referred to the following articles and cases. While not exhaustive, they provide additional pertinent information regarding discovery directed to the corporate defendant.
ARTICLES:
Campbell, James M., Corporate Responses To Massive Discovery Demands, DRI Seminar Materials
“Products Liability” (February 1996).
Cymrot, Mark A., The Forgotten Rule, 18 Litigation No. 3, p. 6 (Spring 1992).
Davis, Richard W., Difficult Task: Defending Defendant’s President/CEO at Deposition or Trial, Dill
Trial Techniques Seminar.
Elbein, Bradley M., How Rule 30(b)(6) Became A Trojan Horse: A Proposal For A Change, FICC
Quarterly 365 (Spring 1996).
Harkins, P.N., Ill, How To Mount An Effective Defense Of Company Employee Depositions, 58
Defense Counsel Journal No. 2, p. 153 (April 1991).
Herlihy, Thomas M., Some Further Thoughts On Preparing Company Witnesses For Depositions, Dill
Life & Health News p. 5 (May 1993).
Massey, M. Minnette, Depositions of Corporations: Problems and Solutions - Fed. R. Civ. P. 30(b)(6),
1986 Ariz. St. L. J. 81(1986).
Preuss, Charles F. and Collins, Erika C., How To Avoid, Control Or Limit Depositions Of Top Executives, Defense Counsel Journal, Vol. 63, No. 2, p. 213 (April 1996).
Schoemaker, Donald K., Document Collection, Review, and Production, For The Defense, p. 9 (January 1995).
Winton, James C., Corporate Representative Depositions Revisited, 65 Baylor L. Rev. 938 (2013).
Endnotes
1
This Rule currently provides that:
In its notice or subpoena, a party may name as the deponent a public or private corporation, a partnership, an association, a governmental agency, or other entity and must describe with reasonable particularity the matters for examination.
The named organization must then designate one or more officers, directors, or managing agents, or designate other persons who consent to testify on its behalf; and it may set out the matters on which each person designated, will testify....
The persons designated must testify about information known or reasonably available to the organization....
Fed. R. Civ. P. 30(b)(6).
Jacobs Vehicle Equip. Co. v. Pac. Diesel Brake Co., No. 96-MC-128, 1996 U.S. Dist. LEXIS 17776, at *6-7 (E.D. Pa. Nov.
27, 1996) (where 30(b) (6) notice would require non-party to identify documents responsive to 40 separate requests
and provide testimony on 8 broad topics of inquiry, notice was “not lacking in particularity” although the areas of
inquiry may have been overbroad); Graco Children’s Prods. v. Century Prods. Co. No. CIV. A. 93-6710, 1996 U.S. Dist.
LEXIS 10356, at *96-97 (E.D. Pa. July 23, 1996) (Rule 30(b)(6) notice was sufficiently particularized which requested
(1) testimony regarding steps taken by defendant in obtaining counsel’s opinions respecting patents, documents and
things supplied by defendant to counsel in making evaluation of infringement, (2) communications with counsel
regarding preparation of counsel’s opinion regarding infringement, and (3) reliance on counsel’s opinion); Marker
v. Union Fidelity Life Ins. Co., 125 F.R.D. 121, 125-26 (M.D.N.C. 1989) (plaintiff ’s 30(b)(6) request for person knowledgeable about defendant’s claims processing and claims records, general file keeping, storage and retrieval systems
2
was specific and understandable); Mitsui & Co. (U.S.A.). Inc. v. P. R. Water Res. Auth., 93 F.R.D. 62, 66 (D.P.R. 1981)
(notice was sufficiently particularized which generally informed defendant of matters about which inquiry would be
made during 30(b)(6) deposition); Scovill Mfg. Co. v. Sunbeam Corp., 61 F.R.D. 598, 603-04 (D. Del. 1973).
3
Lockheed Martin Corp. v. L-3 Comms. Corp., No. 6:05-cv-1580, 2007 U.S. Dist. LEXIS 52658 (M.D. Fla. July 22, 2007).
While some courts have granted protective orders with respect to Rule 30(b)(6) deposition notices asking a corporate party to produce a representative to testify about facts underlying causes of action asserted in a case, other courts
have permitted the Rule 30(b)(6) depositions to proceed. The resolution depends on the facts and procedural status
of the case. This court ultimately ordered that the defendant produce corporate representatives prepared to testify
regarding the facts called for in the deposition notice.
4
The notice at issue sought testimony as to (1) the bases for the RTC’s claims that the defendants were negligent,
grossly negligent or breached their fiduciary duties; (2) the source, usage, and content of the prudent underwriting
standards and guidelines referred to in the RTC’s complaint; and (3) the damages claimed by the RTC, including the
causes and calculation thereof.
5
Contrary to some commentators’ claims, the 30(b)(6) deposition was never meant to replace other discovery devices;
rather, it was enacted as “an additional, supplementary and complimentary [sic] deposition process designed to aid in
the efficient discovery of facts.” Mitsui & Co. (U.S.A.), Inc. v. P. R. Water Res. Auth., 93 F.R.D. 62, 65 (D.P.R. 1981). See
also Advisory Committee’s Explanatory Statement Concerning Amendments of the Discovery Rules, 48 F.R.D. 487,
515 (1970) (stating that the procedure outlined by Rule 30(b)(6) was intended to “supplement[] the existing practice
whereby the examining party designates the corporate official to be deposed...[and] should be viewed as an added
facility for discovery, one which may be advantageous to both sides as well as an improvement in the deposition process”).
6
The foregoing cases address the propriety of “contention interrogatories” in lieu of a 30(b)(6) deposition. To the extent
the areas of inquiry in a notice of deposition can be analogized to “contention” interrogatories, an argument for a protective order can be made particularly when such information is sought early in the litigation, before significant discovery has taken place or the defendant has had an opportunity to articulate and develop fully the theories of its case.
There “is considerable support for deferring contention interrogatories until the end of the discovery period. . . . The
party serving contention interrogatories bears the burden of proving how an earlier response assists the goals of discovery....” B. Braun Med. v. Abbott Lab., 155 F.R.D. 525, 527 (E.D. Pa. 1994); see also In re Convergent Techs. Sec. Litig.,
108 F.R.D. 328, 335-36 (N.D. Cal. 1985) (contention interrogatories better used “near the completion of discovery
and after utilization of other discovery devices”); but see In re. Douglas Asphalt Co., No. 09-51272, 2010 Bankr. LEXIS
2069 (Bankr. S.D. Ga. June 10, 2010) (where Defendant objected to certain topics in the notice of a 30(b)(6) deposition on the basis that contention interrogatories were more appropriate than a 30(b)(6) deposition, the court held that
the manner of discovery served by plaintiffs was for the plaintiffs to decide, noting that while the court may alter the
manner of discovery as it deems appropriate pursuant to Rule 26(c)(1)(C), the defendant did not show good cause for
the court to prescribe a discovery method other than the one the plaintiffs selected); see also Protective Nat’l Ins. Co.
v. Commonwealth Ins. Co., 137 F.R.D. 267 (D. Neb. 1989) (holding that a Rule 30(b)(6) deposition, and not contention
interrogatories, were more appropriate where the 30(b)(6) designee had expertise to answer questions.)
7
As discussed at p.1-27, infra, however, specific corporate representatives can be designated to testify on behalf of the
corporation through Rule 30(b)(1) and, if such representatives qualify as officers, directors or managing agents, their
testimony will be binding on the corporation.
8
Some courts have expansively interpreted and commentators have urged an expansive interpretation of what information is considered “reasonably available” to a corporation. See In re Indep. Serv. Orgs. Antitrust Litig., 168 F.R.D.
651, 653 (D. Kan. 1996) (defendant’s 30(b)(6) deposition of plaintiff regarding alleged redactions of serial numbers
from photocopied software demonstrated that plaintiff had not “exhaustively investigated the alleged redactions” and
that the deponent had not contacted a number of individuals who had information about the redactions; court concluded that “Xerox is entitled to a more thorough investigation and attempt to comply than it appears [deponent] has
made to date”) (emphasis added). Cymrot at 7 (“[A] deponent must search its own files, interview its own witnesses,
and produce binding answers at a deposition.”); Massey at 94 (corporation may be required to acquire information
from former employee who is knowledgeable about matters sought to be discovered under the “reasonably available”
language of 30(b)(6)); In re Anthracite Coal Antitrust Litig., 82 F.R.D. 364, 368-69 (M.D. Pa. 1979).
9
Rule 37(d) provides, in pertinent part: “If a party or an officer, director, or managing agent of a party or a person designated under Rule 30(b)(6) or 30(a) to testify on behalf of a party fails (1) to appear before the officer who is to take the
deposition ... the court in which the action is pending on motion may make such orders in regard to the failure as are
just,” including ordering that certain facts be taken as established, refusing to allow the disobedient party from supporting or opposing a designated claim or defense or prohibiting the party from introducing certain evidence at trial, or striking out pleadings, staying the proceedings, or rendering judgment by default against the disobedient party.
Not all courts, however, have espoused such an absolute view. See Phillips v. Manufacturers Hanover Trust Co., No. 92
Civ. 8527, 1994 U.S. Dist. LEXIS 3748, at *13 (S.D.N.Y. Mar. 29, 1994) (where 30(b)(6) deposition notice sought testimony about the “employment of consultants, employees and temps,” defendant would not be sanctioned for proffering
deponent who lacked specific factual information; deposition notice was very general and plaintiff could have tailored
notice more narrowly or submitted an additional notice aimed at particular subjects); EEOC v. Am. Int’l Grp., Inc., No.
93 Civ. 6390, 1994 U.S. Dist. LEXIS 9815, at *8-9 (S.D.N.Y. July 18, 1994) (fact that corporate representative for 30(b)
(6) deposition was unable to answer certain questions did not render him inappropriate designee: “Rule 30(b)(6) is
not designed to be a memory contest. It is not reasonable to expect any individual to remember every fact in [plaintiff ’s] investigative file”); Zappia Middle E. Constr. Co. v. Emirate of Abu Dhabi, No. 94 Civ. 1942, 1995 U.S. Dist. LEXIS
17187, at *26-27 (S.D.N.Y. Nov. 17, 1995) (in order to impose sanctions for failure to provide adequately prepared
30(b)(6) witness, “inadequacies in a deponent’s testimony must be egregious and not merely lacking in desired specificity in discrete areas”). But see Wilson v. Lakner, 228 F.R.D. 524 (D. Md. 2005) (depending on the nature and extent
of obfuscation by a Rule 30(b)(6) deponent, non-responsive testimony given by the deponent (e.g. “I don’t know”)
may be deemed binding on the corporation so as to prohibit it from offering contrary evidence at trial. Even to the
extent that contradictory evidence might be permitted at trial, the Court could both permit cross-examination of any
witness who contradicted the sworn testimony of the 30(b)(6) witness or witnesses and order the witness to testify
further why in good faith opposing counsel was not apprised of the amendments prior to trial). See also Wachovia
Sec., LLC v. Nola, LLC, 248 F.R.D. 544 (N.D. Ill. 2008) (Rule 30(b) (6) does not allow a corporation to designate a corporate representative, then throw up its hands when the designee refuses to participate and claim it has done its part.
On the contrary, implicit in designating a Rule 30(b)(6) representative who is not an employee or managing agent, is
that the witness will be able and willing to answer questions relating to the information sought.)
10
The district court in Paparelli based its holding on three grounds. First, it concluded that, because the purpose of Rule
30(b)(6) was to afford the examining party the ability to obtain deposition testimony on the designated subject matters,
it made no sense for a party to designate its proposed topics of inquiry, have the corporate defendant provide a knowledgeable individual on that subject, and then question the representative “about matters totally different from the ones
listed in the notice.” Paparelli, 108 F.R.D. at 730. Second, the district court determined that one of the goals of Rule 30(b)
(6), having a corporate designee prepared to answer question on certain subject matters, would be thwarted if the designee could be examined on topics wholly unrelated to those on which he is prepared to testify. Id. at 730. Finally, the court
concluded that the requirement that the notice list the matters upon which examination is requested “with reasonable
particularity” would be meaningless if the deponent could be examined on relevant, but undesignated, topics. Id.
11
Rule 612 is applicable to depositions pursuant to Rule 30(c). See Redvanly v. Nynex Corp., 152 F.R.D. 460, 470, n.5
(S.D.N.Y. 1993).
12
13
Rule 30(b)(1) provides in pertinent part:
A party who wants to depose a person by oral questions must give reasonable written notice to every other party. The
notice must state . . . if known, the deponent’s name and address. If the name is unknown, the notice must provide a
general description sufficient to identify the person or the particular class or group to which the person belongs
14
When drafting an affidavit supporting any claim that the affiant lacks personal knowledge, some courts have felt that
anything short of an unequivocal statement regarding the executive’s knowledge can be considered insufficient to
grant a protective order. Haber v. ASN 50th St., LLC, 272 F.R.D. 377, 383 (S.D.N.Y. 2011) (refusing to issue a protective
order where corporation failed to submit affidavits attesting to an executives lack of knowledge); Horsewood v. Kids
“R” Us, No. 97-2441-GTV, 1998 U.S. Dist. LEXIS 13108 (D. Kan. Aug. 13, 1998) (finding that an affidavit which asserts
the executive is too busy to participate in a deposition is insufficient to, issue a protective order); but see Amherst
Leasing Corp. v. Emhart Corp., 65 F.R.D. 121, 122 (D. Conn. 1974) (finding that executives should establish lack of personal knowledge in a deposition rather than through an affidavit).
Daubert—Practical Approach
to Understanding Daubert and
Challenging Expert Opinions
Mary Nold Larimore
Ice Miller LLP
One American Square, Suite 2900
Indianapolis, IN 46282
(317) 236-2407
(317) 592-4688 [fax]
[email protected]
Mary Nold Larimore joined Ice Miller in 1980 wherein her primary practice
concentration is in litigation, focusing on product liability litigation, the defense of
pharmaceutical and drug and device manufacturers, chemical companies, toxic tort
litigation, commercial litigation, and general liability litigation. Mary Larimore has
served as national, regional and local counsel in drug, device and chemical exposure
litigation, as well as expert witness counsel. She regularly addresses scientific,
epidemiologic and complex medical issues in multijurisdictional litigation. Mary
Larimore was the first woman from the state of Indiana to be inducted as a Fellow
in the American College of Trial Lawyers. She recently testified before the Federal
Rules Advisory Committee on the proposed changes to the federal rules relating to
discovery. She served as Chair of the Supreme Court Committee on Rules of Practice
and Procedure. She was appointed to the Indiana Supreme Court Committee on
Character and Fitness for the State Board of Law Examiners. She is a member of
the National Center for State Courts (recently appointed to the Lawyers Executive
Committee), Lawyers for Civil Justice, the International Association of Defense
Counsel; and Defense Research Institute.
Daubert—Practical Approach to Understanding
Daubert and Challenging Expert Opinions
Table of Contents
I. Scope of Daubert.........................................................................................................................................193
II.Post-Daubert Supreme Court Decisions....................................................................................................194
III. Practice Pointers.........................................................................................................................................194
IV.
Weisgram v. Marley, 528 U.S. 440 (2000)..................................................................................................194
V.
Daubert Criteria..........................................................................................................................................194
VI. Cross-Examination of Plaintiff ’s Expert Under Daubert.........................................................................196
VII.Preparation..................................................................................................................................................196
VIII. Analyze Progression of Expert’s Opinion..................................................................................................197
IX. Preparing for Daubert Challenge...............................................................................................................197
X. Give Expert a Quiz......................................................................................................................................197
XI. Professional Medical Societies...................................................................................................................197
XII. Investigate the Basis of Expert’s Opinion..................................................................................................198
XIII. Medical Testimony: Treating Physicians...................................................................................................198
XIV. Limit Expertise............................................................................................................................................199
XV. Treating Physicians.....................................................................................................................................199
XVI. Focus Early on Daubert Questions............................................................................................................199
Daubert—Practical Approach to Understanding Daubert and Challenging... ■ Larimore ■ 191
Daubert—Practical Approach to Understanding
Daubert and Challenging Expert Opinions
I. Scope of Daubert
A.Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993).
1. The Court as a “gatekeeper” on admissibility of expert testimony.
2. Preventing the jury from having to listen to and evaluate “junk science.”
3. Tool for achieving summary judgment.
4. Tool for challenging class certification.
B.Daubert Criteria.
1. Whether a theory or technique has been tested.
2. Whether a theory or technique was subjected to peer review and publication.
3. What is the potential rate of error?
4. General acceptance of the theory in the scientific community.
a) Some courts give empirical testing – greater weight.
C. Additional Criteria articulated in post-Daubert decisions.
1. Existence and maintenance of standards controlling the technique’s operation.
2. Relationship of the technique to methods which have been established to be reliable.
3. Qualifications of the expert witness testifying based on the methodology.
4. Non-judicial uses to which the method has been put.
In re: TMI Litigation Cases Consolidated II, 911 F. Supp. 775 (M.D. Pa. 1996) affirmed.
D. Is the Expert Opinion Truly Well Grounded in Scientific Knowledge?
1. Scientific – “implies a grounding in the methods and procedures of science.”
2. Knowledge – “connotes more than subjective belief or unsupported speculation.”
Muzzey v. Kerr-McGee Chemical Corp., 921 F. Supp. 508, 511 (N.D. Ill. 1996)
E. Federal Rule 702. Testimony by Experts.
1. “If scientific, technical, or other specialized knowledge will assist the trier of fact to understand the evidence or to determine a fact in issue, a witness qualified as an expert by
knowledge, skill, experience, training, or education, may testify thereto in the form of an
opinion or otherwise, if (1) the testimony is based upon sufficient facts or data, (2) the testimony is the product of reliable principles and methods, and (3) the witness has applied
the principles and methods reliably to the facts of the case.” Amended, effective Dec. 1,
2000.
2. Amendment to Rule 702 reflects Daubert, and its progeny.
3. Advisory Notes to Rule 702 are “required reading.”
4.DRI Daubert Online.
5. Recommended reading includes Reference Manual on Scientific Evidence, Federal Judicial
Center, 1994.
II.Post-Daubert Supreme Court Decisions
A.General Electric v. Joiner, 522 U.S. 136, 146 (1997). The appellate standard of review of Daubert
decisions is abuse of discretion.
1. Animal studies were so dissimilar to the facts in the case it was not an abuse of discretion
to reject experts’ reliance on them.
2. Epidemiology studies not sufficient basis for experts’ opinion when the data in the study
does not support the opinion.
3. “Conclusions and methodology are not entirely distinct from one another.”
4. “[T]here is simply too great an analytical gap between the data and the opinion proffered.”
B.Kumho Tires Ltd. v. Carmichael, 526 U.S. 137 (1999).
1.
Daubert applies “not only to testimony based on ‘scientific’ knowledge, but also to testimony based on ‘technical’ and ‘other specialized’ knowledge.”
2. Courts can apply other “more specific factors” than the four identified in Daubert.
3.
Daubert list of factors “was meant to be helpful, not definitive.”
4.
Daubert’s questions can help to evaluate the reliability even of experience-based testimony.
III. Practice Pointers
A. Evaluate whether the subject of the testimony properly falls under 702(a) or 702(b) before your
expert prepares a report or provides testimony.
B. Does the testimony fall into an established scientific discipline?
C. Can you point to scientific studies on the subject?
D. Is the testimony more a matter of observation or one on which scientific principles are necessary?
IV.Weisgram v. Marley, 528 U.S. 440 (2000)
A. District court denied Daubert motions to exclude evidence pre-trial and during trial.
B. Appellate court rejected plaintiffs’ experts’ testimony under Daubert.
C. No abuse of discretion when 8th circuit directed entry of judgment for defendant, rather than
remanding for new trial.
V.
Daubert Criteria
A. In evaluating whether the method and basis for opinion are scientifically reliable, address two
issues:
1.
General causation – whether the product can cause the injury.
2.
Specific causation – whether the product did cause the injury.
Muzzey v. Kerr-McGee Chemical Corp., 921 F. Supp. 508, 511 (N.D. Ill. 1996).
B.Qualifications:
1. An expert’s qualifications alone are insufficient to satisfy the reliability requirement. Grimes
v. Hoffman LaRoche, Inc., 911 F. Supp. 775 (M.D. Pa. 1996).
2. One court noted that argument that Daubert requires particular academic “credentials for
an expert witness is radically unsound.” Turf Racing Prods., Inc. v. American Suzuki Motor
Corp., 223 F.3d 585, 591 (7th Cir. 2000).
3. “Determinations on admissibility should not supplant the adversarial process; ‘shaky’
expert testimony may be admissible, assailable by its opponents’ thorough cross-examination.” Gayton v. McCoy, 593 F.3d 610, 616 (7th Cir. 2010).
4. “Experience is the predominant, if not the sole, basis for a great deal of reliable expert testimony.” United States v. Conn, 297 F.3d 548, 556 (7th Cir. 2000).
C. Recent case law addressing qualifications:
1.
Huss v. Gayden, 571 F.3d 442 (5th Cir. 2009). Plaintiffs were successful in a Daubert challenge on admissibility of defense expert’s opinion in a medical malpractice case. On appeal,
the Court held that the defense expert was qualified to testify on general causation and specific causation.
“[T]he most important question is not whether one party’s expert is more qualified than
the other’s, but rather, whether an expert’s testimony is reliable.”
2.
Cruz-Vazquez v. Mennonite General Hospital, Inc., 613 F. Supp. 2d 202 (D. Puerto Rico
2009). Plaintiff ’s expert testimony in a medical malpractice case was successfully excluded
under Daubert because the expert did not currently practice medicine and was not qualified.
“The Court finds that a substantial risk of bias arises when a party proposes to use an
expert who focuses on work in legal cases, rather than on active medical practice.”
3.
Barabin v. Albany International Corp., 2009 WL2578967 (W.D. Wash. 2009). Industrial
hygienist excluded based on deficiencies in his credentials. He received a Ph.D. by mail
nine months after acceptance to the university, and the undergrad program was not accredited in the state.
4.
Wielgus v. Ryobi Technologies, 2012 WL 2921450 (N.D. Ill. 2012). The Court ruled that
expert’s testimony (of saw-stop blades, proffering opinion that injuries would have been
minor had the technology been adopted) passed the Daubert test on the sole basis of
expert’s experience coupled with review of other similar accidents.
5.
Nunez v. BNSF Railway Co., 2012 WL 2874059 (C.D. Ill. 2012). The court barred the
expert’s testimony where during the deposition, expert demonstrated lack of knowledge of
applicable rules, applied the rules without factual support, disregarded objective facts, and
cited insufficient evidence to support his conclusion in his report.
D. Precision: “Broad generalizations are far more difficult to corroborate than precise statements
and have little explanatory power.” In re: TMI Litigation Cases Consolidated II, 911 F. Supp. 775
(M.D. Pa. 1996) affirmed.
E. Logical Consistency: “A valid hypothesis cannot be self-contradictory. It is evident that a
hypothesis that contradicts itself is logically ill-formed and cannot be tested.” In re: TMI
Litigation Cases Consolidated II, 911 F. Supp. 775 (M.D. Pa. 1996) affirmed.
F. Consistency with Accepted Theories: “A hypothesis that is not consistent with accepted theories
should be viewed with great caution.” In re: TMI Litigation Cases Consolidated II, 911 F. Supp.
775 (M.D. Pa. 1996) affirmed.
VI. Cross-Examination of Plaintiff’s Expert Under Daubert
A. General Approach:
1. Define objective in advance.
2. Objectives will differ based on type of expert.
a) Is it a repetitive expert?
b) Is it a legitimate, credentialed expert that is out on a limb in this case?
c) Is it a treating physician who is giving a causation opinion without a scientific base?
B. Type of expert will often dictate the approach.
VII.Preparation
A. Work with own expert.
B. Is the theory tested?
1. Has it been peer reviewed?
2. Is it generally accepted in the scientific community?
C. Identify (and attack) all factual assumptions on which opinion is based.
D.C.V./Education/Training.
1. Formal education in the field.
2. Employment experience in field outside of litigation.
3. Previously been qualified or disqualified as an expert in field.
E. Tests performed in the case.
1. Are they appropriate tests?
2. Was technique scientifically sound?
3. Were results interpreted using sound methodology?
F. Is methodology generally accepted in field?
G. Scope of expert’s factual investigation.
1. There are no short cuts.
2. You have to learn the underlying science.
a) Be humble.
b) Ask questions.
H. May involve many different disciplines.
1.Medicine.
2.Epidemiology.
3.Biostatistics.
4.Engineering.
5.Toxicology.
VIII. Analyze Progression of Expert’s Opinion
A. What did they have in front of them at time of report?
B. What did they have in front of them at a later time?
Practice tip: Consider having your own expert prepare a report that is a “critique” of plaintiff ’s
expert’s report/scientific methodology. This report will help both you and the court analyze the
expert’s proffered opinion.
C. Are portions of expert testimony and reports admissible while other portions of expert
testimony and reports are inadmissible?
Portions of an expert report were excluded because they were beyond the scope of expertise.
Other portions were excluded because they “sound dangerously close to being a legal
conclusion.” Viking Yacht Company v. Composites One LLC, 613 F. Supp. 2d 637 (2009)
IX. Preparing for Daubert Challenge
A. Evaluate C.V.
1. Establish no publications on specific drug, device at issue.
2. Establish no independent research into drug/device before consulted by plaintiff ’s attorney.
3. Establish lack of experience in prescribing drug or implanting device.
4. Establish lack of experience with competitive products.
5. One approach is to ask the plaintiff ’s expert to identify the competitive products used to
treat illness.
a) If the expert doesn’t know, it establishes lack of expertise.
b) If the expert does know, ask them about safety/efficacy issues with regard to those
products – often unable to discuss because focused exclusively on product in lawsuit.
X. Give Expert a Quiz
A. Define terms.
B. Describe molecular structure.
C. Ask them established criteria for diagnosis.
D. Ask them about normal/anticipated levels of test results.
E. May help establish general knowledge is so lacking their opinion cannot be scientifically reliable.
F. Familiar with position of established scientific bodies with regard to the issue.
1. If familiar, do they agree?
2. Did they participate?
3. Have regulatory/scientific bodies sought their participation?
XI. Professional Medical Societies
A. Distinguish between credentialed bodies and organizations where write a check and join.
B. Research organizations and who is a member – who is on board.
C. Research “community” within which they practice.
D. Experts may try to achieve “peer review” criteria by creating their own “peer groups” outside
established field.
XII. Investigate the Basis of Expert’s Opinion
A. Is it objective facts or subjective report of plaintiff?
B. Establish all literature reviewed.
C. Establish all records reviewed.
D. Establish all reports reviewed.
E. If they add information at a later time, looks like searching for data to support a pre-ordained
conclusion.
“Coming to a firm conclusion first and then doing research to support it is the antithesis of the
scientific method.” Claar v. Burlington Northern R.R. Co., 29 F.3d 499, 502-03 (9th Cir. 1994).
F. Establish what they didn’t look at.
G. Attack methodology if it is not complete.
H. Establish which conclusions in literature adopted.
I. Which ones did they ignore?
J. What was basis for rejecting sound peer reviewed studies?
Practice tip: Identify every time they use an article to support their position, yet the authors used
the same data to reach a different conclusion.
K. Find out about previous testimony.
XIII. Medical Testimony: Treating Physicians
A. Reviewed all of plaintiff ’s medical records.
B. Obtain agreement that medical history is important to diagnosis and treatment.
C. Distinguish between objective tests and subjective complaints.
D. Very few tests are pathognomic.
E. Identify symptoms that are common in population.
F. Identify myriad of alternative diagnoses in absence of exposure/ingestion of a product.
G. Did they study peer reviewed literature?
H. Standard scientific practice – traditional medical assessment techniques.
I. Did they perform true differential diagnosis?
J. Did they rule out other possible causes? How?
K. Are they relying on temporal relationship?
L. Temporal relationship inadequate under Daubert as sole basis for cause and effect.
M. Ervin v. Johnson & Johnson
1. Treating physician had no reliable basis for expert opinion on causation.
a) No epidemiological data.
b) No scientifically physiological explanation.
“The mere existence of a temporal relationship between taking a medication and the onset
of symptoms does not show a sufficient causal relationship.” Ervin v. Johnson & Johnson,
492 F.3d 901 (7th Cir. 2007).
XIV. Limit Expertise
A. In beginning of deposition, an expert is more likely to admit to areas which do not have
expertise.
B. Go through relevant disciplines and ask whether they believe expert in these areas.
1. If say yes to everything, undermines them with court.
2. If say no, limit themselves.
C. Identify areas of reports that go beyond expertise of the witness.
XV. Treating Physicians
A. Define concepts/terms.
B. Pick an area in field and quiz them.
C. Distinguish between areas where legitimate controversy in field v. areas where no divergence of
views.
D. Identify people at their institution who are experts.
E. When they have questions, who do they go to?
F. Who would get referrals at their institution? Not them.
G. Identify major researchers in field.
H. Identify leading authors or texts.
I. Ask them last time they studied the issue.
J. Has the issue ever been a research interest?
1.When?
2. Independent research?
3. Reviewed research of others?
XVI. Focus Early on Daubert Questions
A.Research Daubert case law applicable to your facts.
B. Develop strategy to attack opinions in deposition.
C. “Begin with the end in mind.” - Stephen Covey
Some Perspectives From Our Clients
Stacey Dixon Calahan
Takeda Pharmaceuticals USA, Inc.
Deerfield,IL
Stacey Dixon Calahan is Assistant General Counsel at Takeda Pharmaceuticals
USA, Inc. in Deerfield, IL. Ms. Calahan is responsible for a wide variety of litigation
and pre-litigation matters for the company, including commercial, product liability,
employment and patent litigation and government investigations. Before joining
Takeda, she was Corporate Counsel at Baxter International Inc. She also practiced
litigation at Lord, Bissell & Brook LLP Chicago, IL.
Table of Contents
I. Understand the Client’s Objectives............................................................................................................205
II. Understand the Client’s Expectations Regarding Communications.......................................................205
III. Timely Communications............................................................................................................................205
IV. Provide Thoughtful and Practical Advice..................................................................................................205
V. Aim To Simplify the Complex....................................................................................................................205
VI. Do What You Say You Are Going To Do....................................................................................................205
VII. Honest Communications............................................................................................................................206
VIII.Budgets........................................................................................................................................................206
IX. Be a Partner.................................................................................................................................................206
X. Seek Feedback.............................................................................................................................................206
Some Perspectives From Our Clients ■ Calahan ■ 203
I. Understand the Client’s Objectives
A. You need to understand client’s goals for each new matter.
B. You should work with inside counsel to develop strategy to achieve the client’s goals.
C. Communicate constantly with inside counsel on strategy and goals, since both may change
throughout life of the matter.
II. Understand the Client’s Expectations Regarding Communications
A. You should understand who from a team will communicate with inside counsel and when.
B. Before you reach out directly to the business people, talk to inside counsel first. Many times
inside counsel wants to be involved in the interview.
C. When input is needed from a client, understand the lead time the client needs to review materials
III. Timely Communications
A. Never belatedly communicate major events. There should never be any surprises. If an unexpected event arises, it should be immediately communicated to the client.
B. You should proactively update client on routine matters – such as the outcome of hearings, and
significant communications with opposing counsel. Never wait for inside counsel to ask you
what happened.
IV. Provide Thoughtful and Practical Advice
A. If you are communicating unexpected news, be prepared to discuss the next steps to address the
new developments.
B. You should never just disclose the risks of a particular course of action and tell a client “it cannot
be done.” Think of alternatives that can be employed for the client to achieve the goal. Once you
understand the client’s goals, you need to work with the client to achieve those goals
V. Aim To Simplify the Complex
A. Be prepared to give an “elevator speech” about the matter – what is the essence of the dispute?
B. Avoid long emails/voicemails at all costs. Try to distill the information to the most important
elements.
VI. Do What You Say You Are Going To Do
A. If a client asks you to call them, return their phone call. Always be responsive to inquiries.
B. Don’t wait for the client to call you to find out the status of a project that is over-due. If you need
more time make sure you communicate this early.
Some Perspectives From Our Clients ■ Calahan ■ 205
VII. Honest Communications
A. If you wouldn’t want to hire a colleague at your law firm, don’t recommend that inside counsel
hire your colleague.
B. If a mistake is made, be upfront and talk about how you plan to fix the mistake.
C. If it is your responsibility to review bills, make sure the bills are in compliance with the client’s
billing guidelines, and be prepared to discuss the details of the bills.
VIII. Budgets
A. Inside counsel needs dependable budgets. Work with inside counsel on assumptions and keep
the budget realistic.
B. More and more companies are looking at alternative fee arrangements. Be open to these arrangements.
C. Make sure to keep scope of work aligned with budget. If unexpected circumstances arise that
might impact budget, communicate with client
D. If personnel need to be added to the matter, communicate with client first before adding them to
a matter.
E. Outside counsel needs to actively manage all fees (local counsel, experts, vendors, etc)
IX. Be a Partner
A. Offer to have members of the firm come in on various topics/developments in the law (even
areas that don’t relate to the work being done)
B. Educate not only in-house counsel but business folks from time to time.
X. Seek Feedback
A. After major events/hearings have concluded, ask the client for some honest feedback about your
performance.
B. After the matter is closed, ask for an honest assessment of your work and your firm’s work.

Defending Drug and Medical Device Litigation: A Primer for

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