Fairmont The Queen Elizabeth Montreal, Quebec

Transcription

3 7 th A n n ua l Me e t i ng
M a y 15 - 1 8 , 2 0 1 6
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Program Information
Registration Form
Schedule of Events
P re-Meeting Workshop
Information
• Invited Session Details
• C ontributed Paper and Poster
Presentations
• H otel & Travel
Reservation Information
Fairmont The Queen Elizabeth
Montreal, Quebec
www.sctweb.org
General Information
SCT Annual Meeting May 15 - 18, 2016
Sustainable Car Travel
The Fairmont properties in the Québec province have
installed electric vehicle charging stations in partnership
with Hydro-Québec’s Electric Circuit. Electric vehicle users
can now drive worry-free, knowing that a public network
of charging stations is available to meet their needs. Our
charging station is located in the indoor parking.
The Society for Clinical Trials, an international community of
professionals from a variety of disciplines involved with the
design, conduct and analysis of clinical trials, invites you
to attend its 37th Annual Meeting, May 15 – 18, 2016, at
Fairmont The Queen Elizabeth in Montreal, Quebec, Canada.
Travel by Air
The closest airport to Fairmont The Queen Elizabeth is the
Montréal-Pierre Elliott-Trudeau International Airport (YUL)
located 14 miles (22 km) from the hotel.
Visas and Entry Requirements
Visit www.travel.state.gov for information regarding visas
and entry requirements for Canada. You may also contact
the nearest U.S. Embassy in your region.
Transportation Options
Fairmont The Queen Elizabeth
900 René-Lévesque West
Montréal, QC H3B 4A5, Canada
+1 514-861-3511
http://www.fairmont.com/queen-elizabeth-montreal/
Taxi
There is a flat rate of $40 CAD to downtown hotels.
Arrangements for a limousine transfer can be arranged with
the hotel concierge upon request.
Subway
The hotel has direct access to the Bonaventure Metro
Station. There is a hotel entrance from the metro station.
Follow signage.
SCT has secured a rate of $229 CAD single/double at
Fairmont The Queen Elizabeth. The SCT rate is available
through April 13, 2016 or until the hotel block is full. After
that, rooms and rates are subject to availability. Visit www.
sctweb.org for hotel information and reservation links.
Train
The hotel is located directly above Central Station, which is
the stop for VIA Rail, Amtrak and several local trains. There
is a hotel entrance from Central Station. Follow the signage.
Hotel Internet Access
SCT has secured free internet in sleeping rooms for SCT
meeting attendees at the Fairmont The Queen Elizabeth,
which also offers wireless internet connectivity in all public
areas such as the main lobby and lounges. Unfortunately,
due to cost constraints, SCT is not able to secure Wi-Fi
Internet access in the general meeting area.
747 Express Bus
Featuring nine stops in each direction, the 747 service operated by the city of Montréal is provided 24 hours a day, 365
days a year, and offers transportation between downtown
Montréal and Montréal-Pierre-Elliott-Trudeau International
Airport. Tickets are purchased at the cost of $10 inside the
terminal before boarding. When returning, a $10 bus fare
is paid aboard the bus (coins only, bills are not accepted).
Tickets provide travelers with a transit pass valid on the
STM bus and metro network for 24 hours. For more information, visit the STM website.
Parking
The hotel parking areas are owned and operated by Indigo:
Valet parking
Entrance on North side of Belmont Street or on Cathcart
Street:
• $29 per night, taxes extra, departure prior to 4:00 p.m.
• In and out privileges
Self-parking
Entrance on South side of Belmont Street
Fees must be paid at the parking pay stations.
Return Meeting and Membership Forms ONLY to:
Society for Clinical Trials, Inc.
100 North 20th Street, Suite 400
Philadelphia, PA 19103
Tel: +1.215.320.3878
Fax: +1.215.564.2175
Email: [email protected]
Website: sctweb.org
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Annual Meeting Registration
Registration
Early Bird registration is available through April 1, 2016.
Registrations received after this date will not qualify for the
reduced registration fee. Please register online to pay by
credit card (Visa, MasterCard, or American Express). SCT
also accepts payments by personal or company check, which
can be made payable to the Society for Clinical Trials, and
mailed to: SCT, 100 N. 20th St. Suite 400, Philadelphia, PA,
19103. All fees are in U.S. Dollars.
Pre-Meeting Workshop Half Day . . . . . . . . . . . $100 each
Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $300
**To see the list, go to the following:
http://www.sctweb.org/docs/membership/SCT 2015 list of
Developing Countries.pdf
Pre-registration closes May 12, 2016. After May 12, attendees can register onsite when the meeting opens at Fairmont
The Queen Elizabeth on May 15.
Registration Fees
Early Bird registration is available through April 1, 2016.
Registrations received after this date will not qualify for the
reduced registration fee. All fees are in U.S. Dollars.
Full Meeting Registration will include access to mid-morning
and afternoon coffee breaks (Monday – Wednesday), luncheons (Monday and Tuesday) and receptions. Arrangements
for special dietary meals must be made in advance by
contacting SCT Headquarters at [email protected] or
+1.215.599.6633.
Pre-Meeting Workshop Registration
For SCT Members
On or Before April 1 (Early Bird Special!):
Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $475
Guests accompanying meeting participants to luncheons
are required to pay a fee of $40 per luncheon. Please notify
SCT Headquarters of any guests before the meeting by contacting [email protected] or +1.215.599.6633.
After April 1:
Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $575
Cancellation Policy
All cancellations must be written and received at the SCT
office by Sunday, May 1, 2016. Annual Meeting cancellations will be refunded less a $100 administrative fee.
Pre-Meeting Workshop Sessions will be refunded less a
$50 administrative fee. After May 1, NO REFUNDS will be
issued. Refunds will be issued 4 - 6 weeks post conference.
Special requests should be directed to the SCT Office at
[email protected] or +1.215.599.6633.
(Reminder: SCT Annual Dues for 2016 must be paid in full in
order to qualify for the Member Registration Fee.)
For Non-Members
On or Before April 1 (Early Bird Special!):
Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $675
Registration Transfers
Registration transfers MUST be in writing and received by
the SCT Business Office by Sunday, May 1, 2016. After this
date, refunds will not be issued for unused registrations.
Transfers cannot be made onsite.
After April 1:
Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $775
*Non-Member Registration at the Non-Member price
includes SCT membership for June – December 31, 2016.
Onsite Registration
Onsite registration is available for the Annual Meeting;
however, your choice of Pre-Meeting Workshops cannot be
guaranteed. After Thursday, May 12, 2016, attendees must
register onsite in Montreal.
For Students
(Proof of Full Time Student Status must be provided with Registration)
Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $150
Student Non-Member Workshop Half Day . . . . . $75 each
Student Non-Member Annual Meeting . . . . . . . $225
37th Annual Meeting Registration Desk Hours
Sunday, May 15
7:00 AM – 7:00 PM
Monday, May 16
7:00 AM – 5:30 PM
Tuesday, May 17
7:00 AM – 5:30 PM
Wednesday, May 18
7:00 AM – 11:00 AM
Accepted proof of student status: Copy of valid student ID
card, letter from institution registrar, letter from department
head, copy of paid tuition bill for current semester.
For Members from Developing Countries**
Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $200
For Non-Members from Developing Countries**
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Schedule of Events
• Workshops are a separate fee from the Meeting. Please register using the SCT meeting registration form. • Attendees may sign up for up to three workshops (AM and PM Half Day Workshops plus an Evening
Workshop).
* Breaks on Monday, Tuesday, Wednesday, as well as lunch on Monday and Tuesday and the Monday evening
reception are included with Annual Meeting Registration. For Sunday workshops, breaks are included but
lunch is not provided.
For workshop descriptions and faculty listing, see page 7
All information subject to change.
Sunday, May 15, 2016
7:00 AM – 7:00 PM
Registration
Pre-Meeting Workshops
8:00 AM – Noon
Workshop P1
Essentials of
Randomized Clinical
Trials
Part 1:
Clinical Trials Design
and Conduct
1:00 PM – 5:00 PM
Workshop P6
Essentials of
Randomized Clinical
Trials
Part 2:
Basic Concepts in
Statistical Analysis
and Reporting of
Results
7:00 PM – 9:00 PM
Half Day Workshops - Morning
Workshop P2
Clinical Trial
Management in
Multicenter Trails:
Navigating the
Complexities
Workshop P3
Independent
Data Monitoring
Committee Reports:
A Practical Guide
for Reporting
Statisticians
Workshop P4
Platform Trials:
A Vision of the
Future
Workshop P5
Leveraging Online
Technology for
Purposes of
Remote Monitoring
Throughout the
Protocol Lifecycle
Workshop P9
Overview of
Non-Inferiority
Studies
Workshop P10
Modern Approaches
to the Design and
Analysis of PatientReported Outcomes
(PROs)
Half Day Workshops – Afternoon
Workshop P7
Workshop P8
Crafting Clinical Trial
Conducting Valid
Data for Sharing
Trials: The Critical
the Reuse - Moving (and Misunderstood)
from Basic Data
Roles of
Management to
Randomization and
Practicing Data
Complete Follow-Up
Curation
Evening Workshops
Workshop P11
Modern Mediation Analysis in
Randomized Trials
Workshop P12
Protocols in Real Life: Training
Study- Site Staff the GPC Way
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Workshop P13
Cost Effective Analysis
for Clinical Trials
Schedule of Events
Monday, May 16, 2016
7:00 AM – 5:30 PM
Registration
8:00 AM – 5:30 PM
Exhibits
8:00 AM – 8:15 AM
Welcome - SCT President, Wendy R. Parulekar
NCIC Clinical Trials Group. Kingston, ON Canada
8:15 AM – 8:30 AM
Presentation of the Class of 2016 Fellows
9:00 AM – 10:15 AM
Curtis Meinert Lecture – Denis Lacombe, MD, PhD
“European Organization for Research and Treatment of Cancer (EORTC): Vision, Strategic Focus
and Implementation Strategy”
10:15 AM – 10:45 AM
Break: Exhibits/Posters
10:45 AM – 12:15 PM
Invited Sessions I
Invited Session 1
Challenges and
Solutions to the
Coordination and
Conduct of an
Emergency Treatment
Trial
Invited Session 2
Early-Phase Designs for
Contemporary DoseFinding Problems in
Oncology
Invited Session 3
Recommendations
on the Use, Conduct,
and Training of
Data Monitoring
Committees: The
Clinical Trials
Transformation
Initiative’s Data
Monitoring Committee
Project
Invited Session 4
Data and
Biorepositories:
Enhancing
Collaborative Science
Invited Session 5
Missing Data Issues
in Cluster-Randomized
Designs for Pragmatic
Trials: A Practical
Overview
M, TM, E
ST
ST, TM
IS/DM, ST, R
ST
12:15 AM – 1:30 PM Lunch (included with meeting registration)
1:30 PM – 3:00 PM
Contributed Paper Sessions I
CPS 1
CPS 2
CPS 3
Time to Event
Miscellaneous
The Trials and
Analyses in RCTs Statistical Issues in
Tribulations of
RCTs
Study Coordination
ST
ST
CPS 4
Managing Data
Across the Trial
Lifecycle
CPS 5
The Ins and Outs
of Trial Design
IS/DM
M, DM, ST
SC
3:00 PM – 3:30 PM
3:30 PM – 5:00 PM
Invited Sessions II
Invited Session 6
It’s Always Too Early
until Suddenly It’s
Too Late: Designing
Surgical RCTs Relevant
to Patients, Staff, and
Changing Technologies
Invited Session 7
What Happens When
a Trial Is Interrupted?
How to Deal with
Suspension of
Randomization and
Restart Your Trial
Invited Session 8
Courage, Controversy,
and Clinical Trials:
Lessons from the
Ebola Epidemic
M, ST
TM
TM, ST, E
6:30 PM – 8:00 PM
CPS 6
Thomas
Chalmers Student
Scholarship
Presentations
Invited Session 9
Invited Session 10
Design, Conduct
Ethical Challenges in
and Reporting of
Pragmatic Comparative
Pilot and Feasibility
Effectiveness Trials
Studies Carried Out in
Preparation for an RCT
TM, ST
E, M, ST
Reception
*All information/scheduling subject to change.
Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM)
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Schedule of Events
Tuesday, May 17, 2016
7:00 AM – 5:30 PM
Registration
8:00 AM – 5:30 PM
Exhibits
8:00 AM – 9:00 AM
Contributed Paper Sessions II
CPS 7
CPS 8
CPS 9
Statistical Issues Statistical Lessons Coordinating RCTs:
in Non-Inferiority
from Across the
Lessons Learned
Trials
Trial Spectrum
ST
9:00 AM – 10:30 AM
Invited Session 11
Pragmatic Trials
ST
CPS 12
Cluster
Randomized
Trials/CrossProtocol Analyses
IS/DM
M, SC
ST
SC
ST
ST
TM, IS/DM
ST
Invited Session 18
Collaborating with
Patient Advocacy
Groups at the Design
State of Your Clinical
Trial: Why It Is So
Important
Invited Session 19
Use of Mobile Health
Technologies in
Pragmatic Clinical
Trials
Invited Session 20
Innovative Trial
Designs for Precision
Medicine
TM
TM, ST, E
ST
10:30 AM – 11:00 AM
11:00 AM – 12:30 PM
Invited Sessions IV
Invited Session 16
Invited Session 17
Improving Health by Guidance on Specifying
Improving Trials: The
the Target Difference
UK MRC Hubs for Trial (Effect Size) for an RCT
Methodology Research
(HTMR), a Nationwide
Network to Develop
Capacity and Optimize
Trial Design and
Conduct
IS/DM, TM
M, ST
Lunch/SCT Business Meeting (included with meeting registration)
1:45 PM – 2:45 PM
Contributed Paper Sessions III
CPS 13
CPS 14
CPS 15
Systematic
Novel Statistical
Improving
Reviews and Meta
Approaches to
Participant
Analysis
RCTs: stratification,
Involvement in
global outcomes,
RCTs
personalized treatments and mediation
ST, M
CPS 11
Engaging
Communities/
Topic-Specific Trial
Issues
Invited Sessions III
Invited Session 12
Invited Session 13
Invited Session 14
Invited Session 15
Efficient Study Designs Statistical Challenges
Expanding Your
Clinical Trial
in Clinical Research
in Recent Development
Reach: Innovations
Simulations: The When,
of Personalized
and Opportunities for
Where, and What
Medicine -- Through
Remote Participant
Biomarker Subgroup
Visits to Boost
Identification to
Retention and
Companion Diagnostic Enrollment in Research
Device Development
Studies
ST, M, R
12:30 PM – 1:45 PM
CPS 10
Implementation
of Electronic Data
Capture Systems
ST
SC, DM
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CPS 16
Electronic Data
Capture and Data
Visualization
CPS 17
Compliance and
Adherence
CPS 18
Multiplicity in RCTs
IS/DM, R
ST
ST
Schedule of Events
2:45 PM – 3:15 PM
Break/Exhibits/Posters
3:15 PM – 4:45 PM
Invited Sessions V
Invited Session 21
Challenges of
Implementing an
Adaptive Design in
an Academic Network
Setting
Invited Session 22
Streamlining
Clinical Trials: The
Practicalities
Invited Session 23
Statistical Challenges
in Immuno-Oncology
Invited Session 24
Building the Clinical
Trials Enterprise of the
Future
Invited Session 25
Prospective Individual
Participant Data MetaAnalysis
ST, M, TM
ST, TM, R
ST, M
IS/DM, ST, R
ST, M
4:45 PM – 6:00 PM
Trial of the Year - The Learning Early about Peanut Allergy (LEAP) Trial
Wednesday, May 18, 2016
7:00 AM – 11:00 AM
Registration
8:00 AM – 9:00 AM
ounders Lecture - Richard Stephens
F
“Patients as Cancer Research - Walking the Walk in the UK”
9:00 AM – 9:15 AM
Break
9:15 AM – 10:45 AM
Invited Sessions VI
Invited Session 26
The International
Behavioural Trial
Network (IBTN): An
International Effort to
Improve the Rigor and
Impact of Behavioral
Clinical Trials
Invited Session 27
FDA IND Reporting
Rule Compels a New
Dialog among the
DMC, Sponsor, and
FDA
Invited Session 28
Central IRBs:
Implementation,
Effectiveness, and
Optimization
Invited Session 29
Use of Administrative
and Registry Data in
Clinical Trials
Invited Session 30
Crossover Trials: New
Perspectives and
Practical Implications
for an Efficient Design
TM
M, ST
M, ST, R, E
M, R, E, ST
ST, M
10:45 AM – 11:00 AM
Break
11:00 AM – 12:30 PM
Contributed Paper Sessions IV
CPS 19
CPS 20
CPS 21
Statistical
Statistical Issues
Trial Management
Approaches in
in Cancer and
& Study
Stepped Wedge
Adaptive Trials
Coordination
Designs
Across the Trial
Lifecycle
ST
ST
DM, SC
CPS 22
Managing Data in
the 21st Century
CPS 23
Pragmatic Trials/
Stepped Wedge/
Missing Data
CPS 24
Regulatory and
Ethical Issues in
Trials
IS/DM, SC
ST
R, E
*All information/scheduling subject to change.
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Pre-Conference Workshops
May 15, 2016
Half Day Workshops – Morning
Workshop P1
Essentials of Randomized Clinical Trials Part 1 - Clinical Trials Design and Conduct
8:00 AM – Noon
Part 1 (AM) and Part 2 (PM) of the “Essentials of Randomized Clinical Trials” workshop are distinct and can
be taken individually or together. Although Part 1 is not a prerequisite for Part 2, the two workshops are
complementary.
This workshop is an introduction to design and conduct of clinical trials. Statisticians and non-statisticians
working in trial-related jobs wishing a more full understanding of the basic concepts used in modern clinical trials
would benefit from this course. Real-world examples are used to demonstrate essential tenants of clinical trial
methodology.
The following specific topics are covered:
• Rationale for Clinical Trials, Clinical Trial Phases, Equipoise
• Most Common Trial Designs
• Key issues in the design of a RCT
• Ethics, Informed Consent, and Patient Safety
• Choice of Endpoints
• Randomization
• Data Collection, Routine Monitoring and Reporting, and Quality Control
Target Audience: The workshop is intended for those with little previous experience or formal training in
clinical trials as well as those who have some basic clinical trial experience but desire a better fundamental
understanding of the methodological principles and concepts involved in clinical trials.
Goals:
1. To explain in simple English the basic concepts behind clinical trial methodology, with real-world examples
to illustrate these concepts.
2. A
ttendees should be able to describe the essential elements of clinical trials and use this knowledge to
contribute as a researcher and collaborator in the successful conduct of a clinical trial.
Faculty:
Laura Lovato, Wake Forest University
Michele Melia, Jaeb Center for Health Research
Yves Rosenberg, National Heart, Lung, and Blood Institute, NIH
Workshop Organizers: Laura Lovato, Wake Forest University
Paul Wakim, Clinical Center, NIH
Workshop P2
8:00 AM – Noon
Clinical Trial Management in Multicenter Trials: Navigating the Complexities
There are many partners involved in the design and implementation of multicenter clinical trials. These include
the sponsor, participating clinical sites, vendors, regulatory bodies, as well as contract research organizations
or academic coordinating centers. In order to implement trials efficiently and achieve high quality data,
there must be good harmonization of efforts among all partners. These include study start-up, ongoing trial
activities, drug/device and supply management, training and certification, data collection, on-site monitoring,
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May 15, 2016
safety management, regulatory review, and performance monitoring. The first issue to be worked out is who is
responsible for what? Then, are they aware of their responsibilities? Followed by, how do we all help each other
achieve our responsibilities? This workshop will present different techniques and models for communication
utilized in multicenter clinical trial management to promote harmonization. This workshop will also highlight
the complexities of conducting international and genomically-driven trials. Scenarios will be presented such
as building data systems and integrations across multiple systems, enrolling the first subject, adverse event
reporting, monitoring visits, different models for education and training, and preparing a DSMB report. These
will be examined from multiple partners’ perspectives. Tips and tools will be provided to promote harmonization.
Target Audience: Principal Investigators, Study Coordinators, Statisticians, Information Technology Managers,
Project Managers, Data Managers, and Site Monitors.
Goals: To provide the audience with tools and tips to achieve better harmonization of efforts to successfully
implement and conduct from start to finish multicenter clinical trials from all partner perspectives..
Faculty: Marianne Kearney Chase, Massachusetts General Hospital
Leigh Ann Chamberlin, Cincinnati Children’s Hospital
Michelle Mahoney, Mayo Clinic
Shauna Hillman, Mayo Clinic
Workshop Organizers:
Dixie Ecklund, University of Iowa
Sumithra Mandrekar, Mayo Clinic
Workshop P3
8:00 AM – Noon
Independent Data Monitoring Committee Reports:
A Practical Guide for Reporting Statisticians
In many clinical trials, an Independent Data Monitoring Committee (IDMC) is responsible for safeguarding
participant safety and trial integrity. To discharge these responsibilities, the IDMC relies on multiple sources of
information, but none is so important as the IDMC Interim Report, the comprehensive report on emerging trial
data received at regular intervals from a reporting statistician or statistical group.
Providing these reports to IDMCs is a daunting task, and good advice on best reporting practices is hard to find.
Because of the confidential nature of IDMC operations, sponsors and CROs may have a limited understanding
of how IDMCs actually use these reports, and IDMC members themselves frequently find it difficult to articulate
their needs before seeing actual displays of real data. Usually, the burden falls on the reporting statistician to
take an active role in providing the most effective reports to IDMCs.
This workshop will deal with practical issues related to preparing IDMC Interim Reports that best meet the
needs of the IDMC. We have had years of collective experience serving on and reporting to IDMCs. We will use
insights we have gained – and opinions that we have – to discuss what experienced IDMC members look for in
IDMC Interim Reports. We will describe general analytic techniques most applicable to reporting on interim data.
We will demonstrate principles of presentation and organization that facilitate IDMC review (sample tables of
content, merits of small and large reports, executive summaries, etc.). We will look specifically at techniques for
presenting analyses of common types of clinical trial data (e.g., enrollment and disposition, adverse events, and
laboratory measures). Recurring themes will include the essential differences between IDMC Interim Reports and
final Clinical Study Reports; the relative merits of timeliness versus cleanliness in data and analysis; and the
importance of flexibility and adaptability in IDMC reporting to meet IDMC needs as they evolve over the course
of the trial.
Target Audience: The target audience includes statisticians who report to IDMCs, sponsors and CROs who are
responsible for providing data to these reporting statisticians, and members of IDMCs who want to learn what
to expect (and demand!) from IDMC Interim Reports.
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May 15, 2016
Goals: To help participants understand:
• how IDMCs use IDMC Interim Reports and what they expect from a well prepared report
• the differences between IDMC Interim Reports and other trial reports
• the challenges of analyzing interim data and the balance between timeliness and cleanliness
• a typical table of contents for such a report
• organizational techniques that encourage efficient IDMC review
• the role of flexibility in the reporting process
• how Sponsors and CROs can facilitate the reporting statistician’s job of reporting to the IDMC
Faculty: Janet Wittes (Moderator), Statistics Collaborative Inc.
Kevin Buhr, University of Wisconsin - Madison
Janelle Rhorer, Statistics Collaborative Inc.
Matt Downs, Statistics Collaborative Inc.
Jean Rouleau, Montreal Heart Institute
Workshop Organizer:
Kevin Buhr, University of Wisconsin – Madison
Workshop P4
Platform Trials: A Vision of the Future
8:00 AM – Noon
Traditionally, clinical trials have been designed to evaluate a single treatment in a homogeneous group of
patients. However, such trials do not provide the physician with the necessary information to make decisions
regarding the best treatment for an individual patient. To overcome this disconnect between trial design and
personalized patient care, we advocate the use of multi-arm platform trials. Platform trials have master protocols
that evaluate multiple treatments across one or more types of patients. Such designs are especially useful for
exploring heterogeneity and interactions of treatment effects, evaluating combinations of treatments, and for
direct comparisons between competing treatments. The sharing of resources in platform trials possibly between
multiple sponsors can greatly reduce costs and increase statistical efficiency. Adaptive platform designs offer
flexible features such as dropping treatments for futility, declaring one or more treatments superior, or adding
new treatments to be tested during the course of a trial. In an era of personalized medicine, platform trials
provide the innovation needed to efficiently evaluate modern therapies.
Target Audience: Statisticians, clinicians, and researchers involved in clinical trial design. The minimum
requirement is an introductory background in clinical trial design and analysis.
Goals: This workshop will
1. Present the motivation and principles underlying platform trials from a physician’s perspective;
2. Demonstrate statistical efficiencies of platform trials relative to traditional strategies;
3. D
escribe real applications and innovative features of platform trials, e.g. pandemic influenza & brain
cancer (GBM);
4. Show how simulations are used in the design stage to refine prospective master protocols;
5. D
iscuss challenges (statistical, logistical, & regulatory interactions) associated with the implementation of
platform trials.
Faculty: Jason Connor, Berry Consultants
Roger Lewis, Harbor-UCLA Medical Center
Ben Saville, Berry Consultants
Workshop Organizers: Ben Saville, Berry Consultants
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May 15, 2016
Workshop P5
8:00 AM – Noon
Leveraging Online Technology for Purposes of Remote
Monitoring Throughout the Protocol Lifecycle
When you think of monitoring a clinical trial, do you picture a clinical research associate physically traveling
to a research site to initiate or close a study, or to conduct an interim visit? New perspectives on monitoring
emphasize the benefit of more efficient monitoring of data, documents and processes throughout the lifecycle
of a study, and ongoing developments in information technology have expanded the standard repertoire of
monitoring strategies to allow for alternative monitoring approaches.
While traditional on-site monitoring is still valuable and often necessary, many other options are available as
alternatives or supplements for the monitoring of clinical trials. Among these are remote site initiation, remote
consent form monitoring, real-time protocol deviation and Adverse Event monitoring, periodic integrity checks of
data and processes as well as monitoring status reports, and remote site close out visits. These procedures
offer a convenient and affordable way to monitor, allow for more flexibility in scheduling and accessibility (e.g.,
in the case of remote site visits), and enhance the conduct of high-quality studies.
This workshop will outline the range of remote monitoring options, provide general guidelines for designing
remote site visits, and elaborate on a case study for monitoring in a multi-center clinical trial that is part of the
National Institute on Drug Abuse (NIDA) Clinical Trial Network (CTN) studies. This will include hands on exercises
designed to allow attendees to experience the challenges for implementing a real-world remote monitoring plan
integrating a variety of available options and including considerations to participant privacy.
Target Audience: Investigators and Study Coordinators, Clinical Research Associates, Clinical Trial Project
Managers and Training Specialists, Data Managers, Information Technology staff, and other key staff involved in
Clinical Trial implementation or specifically site monitoring in the context of clinical trials.
Goals: The main objective of this workshop is for attendees to learn how to leverage remote monitoring options
as convenient and affordable alternatives or supplements to on-site monitoring solutions. The workshop will
incorporate theoretical principles and active group exercises to review the variety of tools and features available
for use remotely as well as identify the particular sites, studies, conditions and content areas (e.g., data,
processes) that may be most suited for remote monitoring.
Faculty: Donna Brown, Emmes Corporation
Kayla Daniels, Emmes Corporation
Dikla (Dee) Blumberg, Emmes Corporation
Anne Hoen, Emmes Corporation
Ashley Case, Emmes Corporation
Workshop Organizer:
Oscar Moreno, Emmes Corporation
Half Day Workshops – Afternoon
Workshop P6
1:00 PM – 5:00 PM
Essentials of Randomized Clinical Trials –
Part 2 – Basic Concepts in Statistical Analysis and Reporting of Results
Part 1 (AM) and Part 2 (PM) of the “Essentials of Randomized Clinical Trials” workshop are distinct and can
be taken individually or together. Although Part 1 is not a prerequisite for Part 2, the two workshops are
complementary.
This workshop is not an introduction to clinical trials. In fact, it assumes some knowledge of and experience in
clinical trials. Nor is it an introduction to biostatistics. It does not teach how to perform statistical tasks; there
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are no formulas and no proofs. Instead, this workshop explains why these statistical tasks are performed and
what the results mean once the tasks are performed. It focuses on the statistical design and analysis aspects
of a clinical trial and some of the statistical issues encountered when preparing the manuscript for publication.
Statistical issues frequently discussed or requiring collaboration between non-statisticians and the biostatistician
are also addressed.
The following specific topics are covered:
• Intention-To-Treat analysis vs. per protocol
• Overview of hypothesis testing
• Confidence intervals
• Sample size and power
• Data and safety monitoring
• Subgroup analysis
• Reporting results (manuscript preparation)
Target Audience: Non-statisticians with some experience in clinical trials who seek a better understanding of
statistical concepts encountered when conducting a clinical trial.
Goals:
1. To explain in simple English the reasoning and intuition behind basic statistical concepts used in clinical
trials.
2. To improve communication between non-statisticians involved in clinical trials and their biostatisticians.
Faculty: Paul Wakim, Clinical Center, NIH
Workshop Organizers: Laura Lovato, Wake Forest University
Paul Wakim, Clinical Center, NIH
Workshop P7
1:00 PM – 5:00 PM
Crafting Clinical Trial Data for Sharing and Re-use: Moving from
Basic Data Management to Practicing Data Curation
Government agencies, journals, and evolving scientific norms have come to expect and/or require access to data
underlying research activity. Data curation is an ongoing process that can be implemented at points across the
data life cycle. Studies have shown that earlier curation work leads to better documented data and improved use
and re-use. Bringing together experts from the US Inter-university Consortium for Political and Social Research
(ICPSR), a social science data archive, and the NIH-National Heart Lung and Blood Institute (NHLBI) data repository,
accumulated knowledge about data curation and data sharing will be passed along to workshop attendees.
ICPSR is a social and behavioral science data repository established over 50 years ago and makes data
accessible from thousands of research studies including in recent years a number of clinical trial studies. The
NHLBI data repository, established in 2000, shares data collected from approximately 130 studies, more than
90 of which are clinical trials. These kinds of infrastructure developments reflect growing interest in the sharing
of clinical trial data making this workshop a timely, practical activity for many involved in data collection and data
management. There are clear actions that clinical trial teams can take prior to submitting data to a repository to
ensure the usability and safekeeping of valuable data resources. The workshop will cover four main topics: (1)
crafting metadata and data for better use and sharing, (2) evaluating and selecting a repository for your data, and
(3) preparation for and data deposit to a repository and (4) understanding what typically happens after clinical
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trial data are shared (type of investigator who requests data, number of secondary publications produced). This
workshop will also cover the curation of confidential (and/or sensitive) data that cannot by fully DE-identified.
Target Audience: Clinical research investigators, sponsors of clinical research, biostatisticians, data managers,
as well as early career investigators who want to gain hands-on experience with data curation tools.
Goals: Participants in this workshop will learn a variety of data curation steps from a professional data archive
staff that can be implemented into data management workflows as clinical trial data are collected and organized.
Participants should bring a laptop computer to participate fully in this session. Participants will leave with
knowledge and experience of how to review, assess, curate, and promote data collections for long-term access.
Faculty: Amy Pienta, Inter-university Consortium for Political and Social Research (ICPSR),
University of Michigan
Justin Noble, ICPSR, University of Michigan
Sean Cody, National Heart, Lung, and Blood Institute, NIH
Jared Lyle, ICPSR, University of Michigan
Workshop Organizer: Amy Pienta, University of Michigan
Workshop P8
1:00 PM – 5:00 PM
Conducting Valid Trials: The Critical (and Misunderstood)
Roles of Randomization and Complete Follow-Up
The purpose of a randomized clinical trial is to assess whether there is a causal relationship between an
intervention and outcome of interest. While it is commonly believed that the purpose of randomization is to
remove bias in treatment assignments or balance baseline characteristics, we will demonstrate that, in reality,
randomization is the critical design feature that enables us to conclude that observed statistical associations
between interventions and patient responses are causal relationships.
Using easily understood examples, interactive activities and minimal mathematics, we will demonstrate how
randomization is essential to objective assessments of causality, and we will discuss the implications this has
for study design, conduct and analysis. For example, we will explain why the Intention to Treat (ITT) principle is
essential to inference based on randomization and not merely a means to conservatively estimate the “realworld” treatment effect (another popular misconception).
We will address how missing data or incomplete follow-up compromise our ability to draw causal conclusions and
explain why there cannot be a statistical solution to the problem of missing data; the only remedy is to minimize
missingness to the greatest extent possible and to employ sensitivity analyses to try to contain the problem.
As a result, it is critical that clinical coordinators and investigators understand the importance of ensuring that
data are as complete as possible, and it is imperative that studies be designed to ensure that collection of
efficacy, laboratory, adverse event, or other assessments be continued until the planned end of follow-up even
after participants discontinue their treatment.
We will address the impact of non-adherence to assigned treatment on the study results and the conclusions that
may be drawn. Even when subjects are non-adherent to their assigned treatment, the intention-to-treat analysis
still provides valid causal inference regarding the effect of assignment to treatment. While clinical investigators
may have a strong desire to assess the effect of receipt of treatment under conditions of full adherence, we will
show that unless we force subjects to adhere, it is not possible to conduct a trial to measure this effect directly,
and no statistical procedure can recover this effect from a trial without full adherence. In particular, alternatives
to ITT such as “per-protocol” and “as-treated” analyses do not measure this effect. Instead, they merely subvert
the randomization and therefore cannot yield valid causal conclusions.
We will also discuss the role of imbalances in baseline risk factors and why observed (or unobserved) imbalances
do not invalidate trial results. We will consider the role of baseline adjustment in the analysis of trial data and
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the desirability of allocation procedures, such as “minimization” that seek to ensure balance.
Additional topics include: the impact of errors in randomization and other protocol violations; assessments of
safety including the analysis of adverse events; analysis of post randomization subgroups such as survivors or
responders; and implications for the conduct and analysis of non-inferiority trials.
Target audience: Anyone involved in the design or implementation of randomized clinical trials with an interest
in ensuring the quality and integrity of those trials. This includes clinicians, clinic coordinators, statisticians, data
managers, and others. No formal statistical background is required, and both statisticians and clinicians can
expect to benefit.
Goals: To help participants develop a deeper understanding of:
• The rationale and importance of randomization,
• What randomization provides, and what it doesn’t provide,
• The effect missing data has on analysis and the importance of minimizing missingness to the greatest
extent possible,
• The rationale and importance of the ITT analysis and the perils of using non-ITT approaches,
• The implications of randomization for proper study design, conduct, and analysis in a wide range of settings.
Faculty: Thomas Cook, University of Wisconsin, Madison
Kevin Buhr, University of Wisconsin, Madison
T. Charles Casper, University of Utah School of Medicine
Workshop Organizer: Thomas Cook, University of Wisconsin, Madison
Workshop P9
Overview of Non-Inferiority Studies
1:00 PM – 5:00 PM
This workshop gives an overview of many of the issues faced by those designing, running, analysing, presenting
and interpreting studies aimed at showing that a new therapy is ‘no worse than’ (from a practical point of view)
an existing therapy. Such trials are becoming increasingly common and often misused. In March 2010, the FDA
published Draft Guidance in regards to Non-Inferiority Studies; the EMA published guidance in 2006. Frequent
cross-reference to these guidances will be given.
The course will include scientific and regulatory issues, with examples taken from the US and Europe. Examples
of proper implementation and improper application will be given.
The presentations will be at a non-technical level (statistically) but require, as a pre-requisite, a basic level of
understanding of the fundamental principles of clinical trials.
Target Audience: The course is relevant both to statisticians and non-statisticians because the issues to be
covered are more at a conceptual level than a detailed analysis level. It is relevant to those in the pharmaceutical
sector as well as those from government and academia.
Goals: Attendees should understand the purpose and potential benefits of non-inferiority studies and how
they differ from equivalence and superiority studies. Attendees should also understand the extra difficulties
associated with these types of studies, over and above those of superiority studies, including such points as
assay sensitivity, choice of control group, choice of population to study/analyse, choice of endpoint and choice
of non-inferiority margin.
Faculty: Simon Day PhD, Clinical Trials Consulting & Training Limited.
Nicole C. Close PhD, EmpiriStat Inc.
Workshop Organizer: Simon Day PhD, Clinical Trials Consulting & Training Limited.
Nicole C. Close PhD, EmpiriStat Inc.
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May 15, 2016
Workshop P10
1:00 PM – 5:00 PM
Modern Approaches to the Design and Analysis
of Patient-Reported Outcomes (PROs)
This pre-conference workshop provides an introduction to the use and analysis of patient-reported outcomes
(PROs) in clinical trials, integrating up-to-date approaches and examples throughout.
Presentations and discussion will cover approaches for designing and analyzing high-quality studies with PRO
endpoints. A PRO is any report of the patient’s health that comes directly from the patient and may measure a
wide range of outcomes such as symptoms (e.g., pain, fatigue, nausea, etc.), well-being (e.g., physical, mental,
social), quality of life, or treatment satisfaction. PROs are inherently important in this era of patient-centered
healthcare. Specific topics to be addressed include:
• Selection of appropriate tools with introduction of new tools,
• Cross-sectional and longitudinal statistical analysis strategies,
• Considerations for the use of PROs in personalized medicine trials, and
• Current regulatory perspectives on PROs in the drug approval process.
Target Audience: Any clinical trial researcher, statistician, or other staff member who is interested in learning
about PROs in clinical trials. No prior knowledge of PROs is needed. However, this workshop will incorporate
contemporary methods and examples so will be of interest to those with existing intermediate knowledge of
PROs as well.
Goals: Attendees should be able to describe the key elements of designing and analyzing PROs in clinical trials.
Attendees will be given examples and references to assist in integrating modern approaches to PROs in their
own clinical trials.
Faculty: Amylou Dueck, Mayo Clinic
Stephanie Pugh, American College of Radiology
Joseph Unger, Fred Hutchinson Cancer Research Center
Paul Kluetz, US Food and Drug Administration
Workshop Organizer: Amylou Dueck, Mayo Clinic
Evening Workshops
Workshop P11
7:00 PM – 9:00 PM
Mediation Analysis in Randomised Trials
In randomised clinical trials, investigators often aim to assess both whether a particular intervention works (“Does
it work?”), but also what is the underlying treatment mechanism (“How does it work?”). Clinical trial investigators
have a long tradition of designing RCTs to answer the first of these two questions but very little knowledge or
experience of the use of trials to answer the second. Answering the second question, and providing an efficacy
and mechanisms evaluation, requires the use of statistical methods for mediation analysis. This workshop gives
an introduction to these modern mediation analysis methods, specifically in the context of randomised trials. To begin, we will introduce the terminology of causal inference and mediation analysis. We will explain standard
methods for constructing inferences for mediation parameters in the single mediator model, and discuss the
assumptions made by such analyses. These assumptions include restrictions to linear models, no treatment
by mediator interaction, no measurement error in the mediator and no unmeasured confounding between the
mediator and the outcome.
We will then extend the concepts to relax these assumptions. Specifically, we will introduce estimation
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May 15, 2016
approaches for the non-linear case and to allow for a treatment × mediator interactions. We will briefly describe
methods that can deal with measured post-randomisation confounders and unmeasured confounders.
The statistical methods touched on in this course will include structural equation modelling and conducting
mediation analysis by fitting parametric regression models. We will illustrate these using trials of complex
interventions in mental health, and highlight where participants can find out further information. We will discuss
how these methods are currently implemented in statistical software including Stata, R, SPSS and SAS.
Target Audience: Practitioners (clinical trial statisticians and trial clinicians) interested in learning more about
mediation analysis. The course is not aimed at the specialist causal inference audience. Technical details will
be kept to a minimum, and only a basic knowledge of statistics (equivalent to linear regression) is required. No
prior knowledge of any statistical software package is assumed.
Goals:
1. P
rovide an introduction to the terminology of causal inference and mediation analysis, describing both its
potential and outlining the major difficulties.
2. Provide an introduction to contemporary statistical methods for mediation analysis.
3. Illustrate mediation analysis on real examples of trials of complex interventions.
4. Demonstrate how these statistical methods can be implemented within standard statistical software.
Faculty: Richard Emsley, Senior Lecturer in Biostatistics, Centre for Biostatistics, Institute of
Population Health, The University of Manchester, UK
Sabine Landau, Professor of Biostatistics, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, UK
Workshop Organizer:
Richard Emsley, Institute of Population Health, The University of Manchester, UK
Workshop P12
7:00 PM – 9:00 PM
Protocols in Real Life: Training Study-Site Staff the GCP Way
This pre-conference workshop will explore the challenge of qualifying, and training, study-site staff for the
operation of a multisite clinical trial.
Presentations and discussions will cover issues related to the vetting, qualifying, and training of study-site staff
both before, and during, a clinical trial and provide examples used by the Coordinating Centers for an NIH-funded
Network (NeuroNEXT). Specific topics to be addressed will include:
• GCP guidelines related to training
• Standard Operating Procedures (SOPs) related to training
• Tools used to vet the qualifications of both site and staff
• Curriculum and tools used for Investigator Meetings and ongoing training which are applicable to networks
and individuals. We will briefly discuss:
- Template agendas
- The major elements of training; e.g., protocol training, outcomes training, electronic data capture
training, interactive web response system training, drug accountability training
-M
ethods and tools used to train varied personnel with varying time constraints; e.g., clinical study
site PIs and coordinators, outcomes evaluators, pharmacists, lab personnel, ancillary site staff, and
dedicated data entry personnel
- When to re-train?
- Documentation of training
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- The role of existing certifications for compliance and outcome measures
- Training sites to prepare for monitoring
Target Audience: Principal investigators, study coordinators, pharmacists, data managers, and information
technology personnel.
Goals: To explore the full range of study operations-related training methods one can employ for study initiation,
and as-needed. Materials and tools will be presented as the methods used over the lifetime of a study.
Faculty: Trevis Huff, Data Manager, Clinical Trials Statistical and Data Management Center
(CTSDMC), University of Iowa
Richard Peters, Information Technology Manager, CTSDMC, University of Iowa
Michael Bosch, Lead Data Coordination Center Coordinator for NeuroNEXT, CTSDMC,
University of Iowa
Brenda Thornell, Senior Project Manager, Clinical Coordination Center for NeuroNEXT,
Massachusetts General Hospital
Workshop Organizer: Michael Bosch, University of Iowa
Brenda Thornell, Massachusetts General Hospital
Workshop P13
7:00 PM – 9:00 PM
Cost Effective Analysis for Clinical Trials
Cost-effectiveness analysis is of growing importance internationally and nationally. A number of countries make
national formulary coverage decisions by use of such analyses. Nationally, value-based insurance plans use
it to identify what’s of value; some government departments, such as the US Department of Veterans Affairs,
consider it in formulary decisions.
When appropriately designed and analyzed, one source of clinical and economic data for estimating costeffectiveness is randomized controlled trials. This course will review issues in the design of such evaluations
(e.g., what data should be collected? what is the appropriate sample size? how naturalistic should the study
design be?). The workshop will address the applicability of various statistical models (for example, Ordinary
Least Square Models, Generalized Linear Models, Generalized Estimating Equations, etc.,) that are commonly
used for the analysis of cost (and preference score) data. The workshop will also address the analysis and
reporting of sampling uncertainty for cost-effectiveness analysis (acceptability curves, confidence intervals for
cost-effectiveness ratios and net benefits, and value of information).
Target Audience: Individuals interested in designing and analyzing economic evaluations in clinical trials.
Goals: After attending the workshop the participants will be able to
• identify the economic outcomes data that should be collected during the trial,
• determine the sample size required for/power of the cost-effectiveness analysis,
• understand the strengths and weaknesses of alternative methods for analyzing data on costs and qualityadjusted life years, and
• understand methods for reporting sampling uncertainty for cost-effectiveness analysis (acceptability curves,
confidence intervals for cost-effectiveness ratios and net monetary benefit, and value of information).
Faculty:
Jalpa Doshi, Department of Medicine, University of Pennsylvania
Henry Glick, Departments of Medicine and Health Care Management, University of
Pennsylvania
Workshop Organizer:
Kousick Biswas, Cooperative Studies Program, US Department of Veterans Affairs
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All information subject to change
7:00 AM – 5:30 PM
Registration
8:00 AM – 5:30 PM
Exhibits
8:30 AM – 9:00 AM
Welcome - SCT President, Wendy Parulekar
NCIC Clinical Trials Group, Kingston, Ontario, Canada
Presentation of the Class of 2016 Fellows
9:00 AM – 10:15 AM
urtis Meinert Lecture – Denis Lacombe
C
“European Organization for research and Treatment of Cancer (ROC); Vision, Strategic
Focus and Implementation Strategy”
10:15 AM – 10:45 AM
10:45 AM – 12:15 PM
Invited Sessions Time Slot I
10:45 AM – 12:15 PM
Invited Session 1: Challenges and Solutions to the Coordination and Conduct of an
Emergency Treatment Trial M, ST
The Established Status Epilepticus Treatment Trial (ESETT) is a randomized, adaptive, comparative effectiveness
trial of three second-line therapies for the treatment of benzodiazepine-refractory status epilepticus in children
and adults. This trial is conducted in an emergency setting with a short therapeutic window and meets the criteria for exception from informed consent. These operational challenges have created special requirements for
the coordination and conduct of the trial including management of exception from informed consent activities,
management of study drug inventory, and randomization, treatment, and data collection in the emergency room
setting.
This session starts with an overview of the ESETT study design by Jordan Elm, including details on the challenges
encountered with the response-adaptive randomization and age stratification requirements of the study. Next,
Catherine Dillion will review the challenges associated with the coordination of study drug distribution and tracking, as well as implementation of emergency unblinding procedures.
Deneil Harney will address exception from informed consent requirements and the management and results of
community consultation and public disclosure activities for ESETT. Finally, Robert Silbergleit will discuss the challenges associated with implementation of a large emergency trial involving large numbers of treating emergency
department physicians and study team members across the trial network. He will provide specific solutions to
implementation challenges including protocol assist devices, use next boxes, and training.
Speakers:
Chair/Organizer:
Jordan Elm, Medical University of South Carolina
Catherine Dillon, Medical University of South Carolina
Deneil Harney, University of Michigan
Robert Silbergleit, University of Michigan
10:45 AM – 12:15 PM Invited Session 2: Early-Phase Designs for Contemporary Dose-Finding Problems in
Oncology ST
The current explosion of new targeted and immunotherapeutic agents for cancer treatment has challenged statisticians to reconsider early-phase designs developed for cytotoxic agents. The goal of determining the maximum
tolerated dose (MTD) is no longer desirable because novel agents are characterized by a reduced toxicity profile, to the point of being essentially safe within the therapeutic dose range. Moreover, for targeted agents, the
relationship between target effect and toxicity might not be linear, implying that the most efficacious dose might
be below the MTD. Under these circumstances, dose selection should not be based solely on toxicity but also
examine both toxicity and activity.
Recent Phase I trials for single-agent or combination therapy have focused on detecting signals of antitumor
activity, pharmacokinetic/pharmacodynamics (PK/PD) relationships, or on assessing the feasibility and utility of
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biological correlative assays. Progress has been made, yet there is still much confusion about which biological
endpoints to incorporate, and how, to determine the optimal dose and/or schedule of new drugs for Phase II
trials.
Cody Chiuzan will discuss the challenges of early-phase development for targeted- immunotherapy agents and
review the most recent designs proposed for testing these novel therapies. Nolan Wages will describe the
implementation of an adaptive early-phase method for identifying the optimal combination of two oral targeted
inhibitors in an ongoing study. Results of simulation studies demonstrate this method’s ability to effectively recommend optimal combinations in a high percentage of trials with manageable sample sizes.
Arzu Onar-Thomas will focus on special considerations for pediatric populations, particularly regarding dosing
issues and adaptations to the CRM used effectively in a series of multi-institutional Phase I trials conducted by
the Pediatric Brain Tumor Consortium over the past fifteen years. Emily Dressler will conclude with strategies for
identifying the next dose to treat, given the need to balance toxicity and efficacy considerations, in addition to
changing paradigms regarding monotonic dose-toxicity assumptions.
Speakers:
Chair/Organizer:
Cody Chiuzan, Columbia University
Nolan Wages, University of Virginia
Arzu Onar-Thomas, St. Jude Children’s Research Hospital
Emily Dressler, University of Kentucky
Emily Dressler, University of Kentucky
10:45 AM – 12:15 PM Invited Session 3: Recommendations on the Use, Conduct, and Training of Data
Monitoring Committees: The Clinical Trials Transformation Initiative’s Data
Monitoring Committee Project ST, TM
The Clinical Trials Transformation Initiative Data Monitoring Committees Project aims to (1) describe the current
landscape of DMC use and conduct, (2) clarify the purpose of and rationale for using a DMC, (3) identify best
practices for independent DMC conduct, (4) describe effective communication practices between independent
DMCs and trial stakeholders during all phases of DMC activity, and (5) identify strategies for preparing a robust
pool of DMC members. As part of this effort, the project team conducted a survey to assess current use and
conduct of DMCs and training practices for DMC members and then convened focus groups to gain in-depth
understanding of needs and best practices related to DMC use.
Survey and focus group findings were presented at the 2015 SCT Annual Meeting. Subsequently, findings from
these activities were presented to and discussed among a multi-stakeholder group of experts in DMC issues at
an expert meeting. Based on data gathered via these evidence-gathering activities and feedback from discussion
at the expert meeting, the project team has developed recommendations intended to improve the quality and
efficiency of DMCs.
Presenters will introduce the issue, provide a brief project overview, briefly review project findings, and present—
for the first time publicly—new recommendations covering:
1. Role of the DMC, including issues related to DMC access to blinded data and independence.
2. DMC composition, including issues related to conflict of interest and use of patient advocates in DMCs.
3. C
ommunication related to the DMC, including communication between the DMC, trial sponsor, statistical
analysis center, IRBs, and regulatory bodies.
4. DMC charter, including a sample table of contents and points for consideration.
5. T raining of DMC members and statistical analysis center statisticians, including suggested training formats
and apprenticeship opportunities.
Additional tools will also be presented related to specific responsibilities of the DMC.
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Speakers:
Chair:
Organizer:
Karim Calis, FDA/CDR, NIH/NICHD
Raymond Bain, Merck Research Laboratories
Jane Perlmutter, Patient Advocate
Dave DeMets, University of Wisconsin
Annemarie Forrest, Clinical Trials Transformation Initiative
10:45 AM – 12:15 PM Invited Session 4: Data and Biorepositories: Enhancing
Collaborative Science IS/DM, ST, R
Responsibilities for submission to repositories are often held by the data coordinating center in a multicenter
study. Those responsibilities are increasingly complex and resource intense. The utility of the clinical data, biological samples, genetic sequences, and other information is a function of the rigor with which the submissions
are collected, curated, de-identified, stored, and disseminated. Speakers in this session discuss their experiences with repositories.
The first presentation considers the NIH perspective, describing BioLINCC, NHLBI’s biospecimen and data repository. The next four speakers will share examples of challenges and possible solutions encountered during the
archive process. A discussant will summarize the presentations with thoughts for meeting repository requirements in the future.
Speakers:
Discussant:
Chair:
Organizer:
Elizabeth Wagner, NIH/NHLBI
Valerie L Durkalski-Mauldin, Medical University of South Carolina
Suzanne Firrell, George Washington University
Katherine Kirkwood, Mount Sinai Hospital
Sharon Lawlor, University of Pittsburgh
Mei Lu, Henry Ford Health Systems
Shaun Treweek, University of Aberdeen, UK
Kathleen Jablonski and Mary Foulkes, George Washington University
10:45 AM – 12:15 PM Invited Session 5: Missing Data Issues in Cluster-Randomized Designs for
Pragmatic Trials: A Practical Overview M, IS, DM, R
An ever-increasing number of clinical trials are being implemented in a pragmatic setting, at times employing
multilevel interventions randomized to natural clusters or groups of individuals, with outcomes measured at each
level. As with all clinical studies, missing data are an unavoidable feature. Handling this is further complicated
within cluster-randomized designs, to the extent that missing data methods developed for individually randomized
trials require customized adaptations.
While research methodologists have proposed ways to mitigate the impact of missing data for over a decade, the
use of these designs still lags behind this literature, as evidenced by recent systematic reviews. It is not clear
whether investigators involved in recent studies appreciate that their estimates often would only be unbiased
under the rather restrictive assumption that data are missing completely at random. Investigators’ lag in adopting the most appropriate methods for their data may simply reflect convenience: default implementations and
options accessible in commercial software often entail more restrictive assumptions.
This session provides a practical overview of these issues and offers approaches to navigate their potential
pitfalls. Topics to be covered include:
• Comparison of population-averaged and cluster-specific models for the analysis of cluster randomized trials
with missing binary outcomes.
• Analysis of cluster-randomized trials with missing dichotomous outcomes: empirical and simulation results.
• Bayesian methods for modeling non-ignorably missing data in cluster-randomized trials with binary outcomes.
• Inverse-probability-weighted semi-parametric estimation of treatment effect in cluster randomized trials with
missing data.
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• A pattern-mixture model approach for handling missing outcome data in cluster-randomized trials.
David Murray will comment on the presentations and direct discussion with an eye to highlighting implementable
solutions for those engaged in cluster-randomized designs of pragmatic trials that require multilevel modeling.
Speakers:
Chair/Discussant:
Organizer:
Lehana Thabane, McMaster University, Canada
Jinhui Ma, University of Ottawa, Canada
Catherine Crespi, University of California at Los Angeles
Mélanie Prague, Harvard University
Mallorie Fiero, University of Arizona
David Murray, NIH/Office of Disease Prevention
Kenneth Wilkins, NIH/NIDDK
12:15 PM – 1:30 PM Lunch
1:30 PM – 3:00 PM
Contributed Paper Session Time Slot I
CPS 1: Time to Event Analyses in RCTs ST
CPS 2: Miscellaneous Statistical Issues in RCTs ST
CPS 3: The Trials and Tribulations of Study Coordination SC
CPS 4: Managing Data Across the Trial Lifecycle IS/DM
CPS 5: The Ins and Outs of Trial Design M, DM, ST
CPS 6: Thomas Chalmers Student Scholarship Presentations
3:00 PM – 3:30 PM
3:30 PM – 5:00 PM
Invited Sessions Time Slot II
3:30 PM – 5:00 PM
Invited Session 6: It’s Always Too Early Until Suddenly It’s Too Late: Designing
Surgical RCTs Relevant to Patients, Staff, and Changing Technologies M, ST
Multicenter randomized controlled trials (RCTs) in surgery require enormous investment and effort. Challenges
specifically relate to the inclusion of evolving and novel innovations and surgeon skill and expertise. There also is
a need to ensure that interventions are acceptable to patients, surgeons, and other clinical staff. These issues
have hampered the progress of RCTs in surgery, with some never starting and others requiring expensive extensions. Completed and reported trials have been received with disbelief and failed to change practice because
of claims that results would have been different if the interventions had been done by experts using novel techniques or tools. To increase the validity and impact of RCTs in surgery, there is a need to consider these issues
and to develop methods to allow changing technologies and skills to be included in trial design.
In the UK, several initiatives are under way to address these issues. Multidisciplinary collaborations between
trialists, methodologists, and surgeons have been developed to optimize pretrial work and full trials. This session
will provide an overview of these initiatives and consider key issues with illustrated examples.
The first part will consider how surgical innovations may be included in ongoing trials and pilot work to ensure that
the research question is up-to-date and relevant. This will be illustrated by two examples: recent modification of
a two-group trial to a three-group trial in bariatric surgery (the By-Band-Sleeve Study) and use of mixed-methods
pilot work to inform the design of an RCT (the Bluebelle Study).
The second part will focus on how to design RCTs to incorporate innovation, surgeon preference, and expertise.
Examples include an optional expertise paired design that allows surgeons with and without preferences to participate (the Topkat Trial) and a definitive RCT with a nested IDEAL Phase IIB study (the ROMIO Trial). The IDEAL
framework described how novel surgical interventions may be evaluated, and this example is one of the first of
its kind.
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Speakers:
Discussant: Chair: 3:30 PM – 5:00 PM
David Beard, University of Oxford, UK
Natalie Blencowe, University of Bristol, UK
Jane Blazeby, University of Bristol, UK
Jenny Donovan, University of Bristol, UK
Leila Rooshenas, University of Bristol, UK
Barney Reeves, University of Bristol, UK
Invited Session 7: What Happens When a Trial Is Interrupted? How to Deal with
Suspension of Randomization and Restart Your Trial TM
There is now a fairly mature literature on early termination of studies for planned reasons. However, a study
may also be put on hold while a specific issue or issues are investigated, with the prospect that the trial can
resume if the problem is satisfactorily resolved. Several factors can cause a clinical trial to be suspended, the
most common being a safety concern, a perceived shift in the risk/benefit balance (or other ethical concerns),
or external factors such as the continued availability of funding or consumables. The catalyst for the trial suspension may even be from a changing interpretation and advice on national treatment guidelines, which may have
political dimensions and involve intense media scrutiny. Such considerations triggered the temporary suspension
in 2014-15 of two surgical trials that looked at surgical interventions for urinary incontinence and prolapse and
were publicly funded by the UK NIHR Health Technology Assessment Programme.
This session will discuss the challenges and solutions related to suspending and restarting a study, based on
the experiences in these and other trials. Rather than a statistical view, this session is about the practicalities
of how to manage such an unscheduled major interruption and maximize the chance of a successful restart.
The first talk will describe how a trial team identifies the issue, assesses the risks and necessary actions, and
then moves to create an initial action plan, communicating with all relevant stakeholders and establishing likely
resource needs and timelines.
The second talk will be about implementing such an action plan and the need for flexibility in adapting to what
can be challenging and rapidly evolving circumstances and demands. The third talk will focus on restarting the
trial, with emphasis on speed and accuracy, and also reassurance and any retraining or education needed, for
example, on protocol changes. The fourth talk will be a summary reflection on what has been learned and offer
suggestions on how trialists can be more prepared in advance for such events.
Speakers: Alison McDonald, University of Aberdeen, UK
Lynda Constable, University of Aberdeen, UK
Tracey Davidson, University of Aberdeen, UK
Mary Foulkes, George Washington University
Chair: John Norrie, University of Aberdeen, UK
Organizer: Lynda Constable, University of Aberdeen, UK
3:30 PM – 5:00 PM
Invited Session 8: Courage, Controversy, and Clinical Trials: Lessons from the
Ebola Epidemic TM, ST, E
As West Africa begins to recover from the devastating Ebola epidemic of 2014-2015, this session offers a look
back at the major studies conducted during the epidemic and discusses the lessons that can be learned about
improving the scientific research community’s response to emerging infectious diseases.
The three main talks will focus on the ethical, methodological, and humanitarian issues of conducting research
during the Ebola epidemic:
• James Neaton will give an overview of PREVAIL I, a double-blind, placebo-controlled, Phase II/III trial that
compared two Ebola vaccines and was conducted in Liberia. He will highlight the difficulties in running such
a trial and the lessons learned, including that simple procedures for randomization and blinding can be
implemented in difficult field conditions. As the only double-blind, placebo-controlled RCT for Ebola vaccines
conducted in West Africa, PREVAIL I provided valuable evidence about vaccine safety and immunogenicity.
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(The waning epidemic resulted in too few events to assess clinical efficacy.)
• Adam Levine will focus on the disconnect and the interplay between the humanitarian mission and the clinical research agenda that occur during an emerging disease epidemic. Much of this disconnect is potentially
due to cultural differences between academic institutions and humanitarian organizations. However, with few
high-quality research studies to guide humanitarian healthcare practice, the differences in culture need to be
overcome to improve both clinical research and humanitarian care, particularly during epidemics.
• Ross Upshur will outline the ethical questions raised about the value and feasibility of clinical research in
the midst of a serious public health emergency. Differences between humanitarian and regulatory worldviews
opened up a discussion on study design. Now that most of the trials have been closed, we can review how
this discussion has changed and what we have learned.
Lori Dodd will summarize the three presentations and facilitate a group discussion between the presenters and
the audience.
Speakers:
Discussant: Chair:
Organizer:
James Neaton, University of Minnesota
Adam Levine, Brown University
Ross Upshur, University of Toronto, Canada
Lori Dodd, NIH/NIAID
Julian Wolfson, University of Minnesota
Erin Gabriel, NIH/NIAID
3:30 PM – 5:00 PMInvited Session 9: Design, Conduct, and Reporting of Pilot and Feasibility Studies
Carried Out in Preparation for a RCT TM, ST
Trials carried out in a health-care setting typically involve complex interventions that require considerable planning if they are to be implemented successfully. Complex interventions are conventionally made up of several
interacting components and present special problems related to their sensitivity to the local context and the
logistics of applying experimental methods in a health-care setting. The UK Medical Research Council’s guidance document on complex interventions emphasizes the importance of thorough groundwork in designing and
evaluating complex interventions and stresses the importance of contextualizing and conceptualizing the problem
at the development stage.
Pilot and feasibility studies can be an essential part of trial preparation. Recent papers have shown a dearth of
pilot studies in the literature that state they are specifically in preparation for a randomized controlled trial, and
that give a clear list of key objectives relating to the pilot phase. Feasibility and pilot studies are conducted to
assess the feasibility and integrity of the study protocol, but the differences between the two are not clear-cut.
This session will provide an overview of the objectives of feasibility and pilot studies, considering issues of study
design and analysis, with useful examples and references. The rationale for the development of CONSORT extension guidelines for pilot trials will be outlined, and Pilot and Feasibility Studies, a new BioMed central journal
arising from this work, will be introduced.
Speakers:
Discussant: Chair/Organizer:
Gillian Lancaster, Lancaster University, UK
Mike Campbell, University of Sheffield, UK
Sandra Eldridge, Queen Mary University of London, UK
Lehana Thabane, McMasters University, Canada
Gillian Lancaster, Lancaster University, UK
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3:30 PM – 5:00 PMInvited Session 10: Ethical Challenges in Pragmatic Comparative Effectiveness
Trials E, ST, M
Standard-of-care randomized controlled trials (RCTs) test the comparative effectiveness of two or more interventions used routinely in medical practice and provide information critical to health-care delivery. However, these
trials raise ethical issues that challenge researchers, research ethics committees, regulators, and sponsors as
they seek to responsibly fulfill their respective roles. In this session, we will address the importance of comparative effectiveness trials as a tool to help patients and practitioners identify more effective treatments and
improve quality, while recognizing the need to control the costs of care.
We will introduce FLUID as a case study of a cluster crossover trial that seeks to compare the impact of two
resuscitation fluids routinely used in emergency departments and intensive care units on patient mortality and
hospital readmissions. We will address the interplay between ethics and statistical design by reviewing alternative design choices and their implications for feasibility, generalizability, and validity. We also will address a
dominant claim in the literature, namely that research entails additional risks compared to clinical practice. We
will argue that this claim pushes the current literature and discourse of the ethics of standard-of-care RCTs in
the wrong direction.
If important research is to proceed, a novel ethical framework for standard-of-care RCTs is required. Working
toward this goal, we will appeal to relevant foundational documents in research ethics, national and international
regulations, and relevant literature to identify gaps and areas where further ethical analysis is required.
Speakers:
Chair:
Organizer:
Dean Fergusson, Ottawa Hospital Research Institute, Canada
Lauralyn McIntyre, Ottawa Hospital Research Institute, Canada
Monica Taljaard, Ottawa Hospital Research Institute, Canada
Austin Horn, Western University, Canada
Charles Weijer, Western University, Canada
Dean Fergusson, Ottawa Hospital Research Institute
Monica Taljaard, Ottawa Hospital Research Institute
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7:00 AM – 5:30 PM
Registration
8:00 AM – 5:30 PM
Exhibits
8:00 AM – 9:00 AM
Contributed Paper Session Time Slot II
CPS 7: Statistical Issues in Non-Inferiority Trials ST
CPS 8: Statistical Lessons from Across the Trial Spectrum ST
CPS 9: Coordinating RCTs: Lessons Learned SC
CPS 10: Implementation of Electronic Data Capture Systems IS/DM
CPS 11: Engaging Communities/Topic-Specific Trial Issues M, SC
CPS 12: Cluster Randomized Trials/Cross-Protocol Analyses ST
9:00 AM – 10:30 AM
Invited Session Time Slot III
9:00 AM – 10:30 AM
Invited Session 11: Pragmatic Trials ST, M, R
Most clinical trials fail to provide the evidence that clinicians need to optimally treat patients. Pragmatic clinical
trials are designed to address this limitation, seeking to inform medical decision-making. Many leaders are thus
urging more pragmatism in clinical trials.
Each of the session’s speakers will focus on an issue related to conducting these trials:
• Merrick Zwarenstein will discuss an ongoing project on empirical studies of pragmatic trials. Using the RCTs
in a large systematic review, he is exploring whether the degree of pragmatism, as measured by the PRECIS2
score, is associated with the effect size and separately with the risk of bias using the Cochrane ROB tool.
These findings will evaluate whether pragmatic trials have a smaller effect size than more explanatory trials,
and whether their improved external validity is at the expense of reduced internal validity.
• Matt Roe will review lessons learned from recently completed pragmatic clinical trials, delineate the key
attributes of pragmatic vs. traditional clinical trials, and discuss strategies for overcoming barriers for the
widespread implementation of pragmatic clinical trials.
• Laura Dember will focus on the advantages and challenges of conducting trials in large numbers of health-care
facilities while relying on highly centralized implementation approaches and data acquired through routine
clinical care. In doing so, she will draw on her experience implementing the Time to Reduce Mortality in Endstage Renal Disease Trial, a large, cluster-randomized pragmatic trial evaluating the effect of hemodialysis
session duration on mortality, hospitalization rate, and quality of life. The trial is being conducted in partnership with the two largest U.S. dialysis provider companies as one of the demonstration projects of the NIH
Health Care Systems Research Collaboratory.
Discussants Dave Demets and Rob Califf will summarize the talks and lead active discussion with attendees.
Speakers:
Discussant:
Chair/Organizer:
Merrick Zwarenstein, Western University, Canada
Matt Roe, Duke University
Laura Dember, University of Pennsylvania
Dave Demets, University of Wisconsin
Rob Califf, FDA
Scott Evans, Harvard University
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9:00 AM – 10:30 AM
Invited Session 12: Efficient Study Designs in Clinical Research ST
Efficient designs can be defined as statistically robust designs that enable quicker and/or lower cost decisions
compared to conventional designs. Efficient design is in fact an umbrella term that encompasses all aspects of
clinical trial conduct and analysis, as well as the design. Hence, an efficient design is a smarter way of running
a trial and can save resources and time in the assessment of new health technologies.
The first talk of this session uses case studies and examples of efficient study design to highlight the benefits of
a range of efficient study designs. It will be highlighted how both using routinely collected data for data collection
and even simple adaptive methods can have an impact on the efficiency of a study. Some of the challenges of
this type of study design will also be discussed. The next speaker will focus on available methods of analysis
following an adaptive design, highlighting issues of bias and accuracy, and exploring the use of such methods
in current trials.
The third talk will consider adaptive study designs and their impact on the economic evaluation of health-care
technologies. It will highlight how by neglecting cost-effectiveness in our adaptive designs, we potentially compromise on the quality of this evidence and miss an opportunity to make our study designs more efficient by using
cost-effectiveness information in interim decision-making.
The final talk will examine a case study that used early time points to inform clinical trial decisions. The speaker
will describe how individual patient data from a previous study and meta-analysis of mean responses can be used
to provide rationale for using an early time point to predict the treatment response at a later time point. In the
case study, use of an early time point improved trial efficiency by potentially reducing study time by 294 days.
Speakers:
Organizer:
9:00 AM – 10:30 AM Steven Julious, University of Sheffield, UK
Sue Todd, University of Reading, UK
Laura Flight, University of Sheffield, UK
Feng Liu, GlaxoSmithKline, US
Steven Julious, University of Sheffield, UK
Invited Session 13: Statistical Challenges in Personalized Medicine:
Through Biomarker Subgroup Identification to Companion Diagnostic Device
Development ST
The future of personalized medicine is highly promising. A number of recently FDA-approved companion diagnostics products are strong evidence of a successful first step. However, there are still considerable statistical
challenges in areas such as exploratory biomarker identification; incorporation of each patient’s clinical characteristic and genomic signature to derive the most accurate diagnosis; and application of prespecified biomarker
or companion diagnostic devices to clinical trials to streamline the development process and maximize efficacy.
How to appropriately identify biomarker subgroups and efficiently move forward to companion diagnostic devices
also remain challenging. A comprehensive and successful solution could only be possible when regulatory agencies, academic researchers, and industry pioneers work together to address issues in the aforementioned areas.
This session serves as a good example how such collaboration and cross-agency thinking could be achieved.
The session focuses on the statistical issues surrounding the development of personalized medicine, spanning
the workflow from early-phase exploratory biomarker subgroup identification to validated biomarker-based companion diagnostic development. Liang Fang will discuss the practical challenges and considerations of searching
a predictive biomarker in the era of personalized medicine and the increasingly fast pace of drug development.
Practical and statistical issues around stratification, cutoff selection for continuous biomarker, co-primary endpoints, and clinical trial designs will be discussed. Options to overcome these issues will also be presented.
Yi Huang will present various statistical challenges in enriched randomized clinical trials, in particular in the areas
of subgroup identification using biomarker information from early phases or prior studies and how to synthesize
results from multiple enriched randomized clinical trials.
Ruixiao Lu will show the power of using genomic information to derive composite biomarker measures that maxi25
mize therapeutic efficacy using patient-specific molecular signatures. She will also make the important distinction
between prognostic and predictive biomarkers and illustrate the appropriate ways to assess clinical impact and
relevance with real-life examples. Laura Yee will provide an overview of companion diagnostics from the regulator’s perspective with the focus on prescreening with a local test. She will also discuss how to address the bias
incurred in such populations.
Speakers:
Discussant:
Chair/ Organizer:
Liang Fang, Gilead Yi Huang, University of Maryland (UMBC and UMB)
Ruixiao Lu, Genomic Health
Laura Yee, FDA
Jing Huang, Veracyte
Rui (Sammi) Tang, Vertex
9:00 AM – 10:30 AM
Invited Session 14: Expanding Your Reach: Innovations and Opportunities for
Remote Participant Visits to Boost Retention and Enrollment in Research
Studies TM, IS/DM
This session will show how five different studies have expanded their reach by conducting more than 60,000
remote study visits to where participants live or work. The rationale, logistics, challenges, and successes will be
discussed for each study. The pragmatic approaches to the design and conduct of these studies exemplify costeffective innovations used to bolster recruitment and retention while simultaneously minimizing subject burden.
Strategies used in these five studies are applicable in domestic and international projects to promote retention
and recruitment in otherwise hard-to-reach populations.
JoAnn Manson will describe design features to optimize cost-efficiency in the large-scale VITamin D and OmegA3 TriaL (VITAL). Susie Day will explain how the Fuel 2 Fight Study achieved a nationally representative sample
of firefighters by going directly to the subjects’ workplaces. Virginia Howard will show how in-home baseline
visits for enrollment in a U.S. national cohort study of stroke risk factors in blacks and whites were achieved in
the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Matthew Curry will report on a
home-visit staffing model used in the Gulf Long-Term Follow-up Study (GuLF STUDY), a prospective cohort study
designed to examine the health effects associated with the cleanup effort surrounding the 2010 Deepwater
Horizon oil spill disaster. Marinella Temprosa will illustrate the use of external examination services to supplement clinical visits for maintaining retention and adherence in the Diabetes Prevention Program Outcomes Study
(DPPOS), a multi-center clinical trial that has been ongoing for twenty years.
Speakers:
Organizers:
JoAnn Manson, Brigham and Women’s Hospital, Harvard Medical School
R. Susie Day, University of Texas School of Public Health, Houston
Virginia Howard, University of Alabama at Birmingham
Matthew Curry, Social Scientific Systems
Marinella Temprosa, George Washington University
Marinella Temprosa, George Washington University
Valerie Donohue, George Washington University
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9:00 AM – 10:30 AM
Invited Session 15: Clinical Trial Simulations: The When, Where, and What ST
Clinical trial costs have increased almost exponentially since the 1990s, with failed clinical trials a major cost
driver. Clinical trial simulations can help to improve efficiency and reduce costs by optimizing various aspects of
clinical trials, including number of patients, effect size, primary outcomes, variance of endpoint measurements,
design choices (for example, parallel vs. crossover, individual-based vs. community-based, adaptive trial design),
inclusion-exclusion criteria, and costs. The focus of this session is on how clinical trial simulations can produce
novel insights to complement traditional statistical methods for clinical trial planning, conduct, analysis, and
interpretation of trial results.
The session will introduce examples of clinical trial simulations for three different disease types: acute viral
infections such as influenza; chronic viral infections such as HIV; and chronic noninfectious diseases such as
Alzheimer’s disease, cardiovascular disease, and chronic obstructive pulmonary disease. Researchers working
on different diseases may apply different methods and paradigms in clinical trial simulations. The talks will also
show how simulations can help in different stages of the drug development process (PK/PD models in drug
design to Phase I/II/III/IV trials).
To encourage the exchange of experiences and ideas, and identify areas of agreement and disagreement about
the use of clinical trial simulations, the talks will be followed by a round-table discussion. Discussion points
include: Should all clinical trials be simulated? What makes a trial simulator valid? When are clinical trial simulations most appropriate (for example, contexts in which independence of individuals is unclear or interim analyses)? Do we need to develop guidelines for using models to simulate clinical trials? If yes, how stringent should
these guidelines be? Do simulators have to be standardized or approved? How can guidelines for clinical trial
simulators be assembled?
Speakers:
Chair:
Organizer:
Benoit Masse, University of Montreal, Canada
Victor De Gruttola, Harvard University
Klaus Romero, Critical Path Institute
Hugo Geerts, In Silico Biology
Carolin Vegvari, Imperial College London, UK
Marie-Claude Boily, Imperial College London, UK
Carolin Vegvari, Imperial College London
10:30 AM – 11:00 AM
11:00 AM – 12:30 PM
Invited Session Time Slot IV
11:00 AM – 12:30 PMInvited Session 16: Improving Health by Improving Trials: The UK MRC Hubs for
Trials Methodology Research, a Nationwide Network to Develop Capacity and
Optimize Trial Design and Conduct IS/DM, TM
The development and implementation of novel methods for trial design, conduct, and analysis are often slowed by
lack of awareness, access to tools, and concerns about added complexity. As a result, clinical trials may not include
improved methods to deliver high-quality data in a timely and cost-effective way.
In 2009, the Medical Research Council (MRC) established the Hubs for Trials Methodology Research (HTMR) to
create a UK-wide regionally distributed research resource to improve the design, conduct, analysis, interpretation,
and reporting of clinical trials. The MRC HTMR Network adds value by supporting investment, collaboration and leadership on a nationwide scale. The network also promotes and encourages collaborative methodological research
relevant to trials to accelerate implementation of the most effective and appropriate methods to improve the quality
of trials and, ultimately, patient care.
This session, presented by members of the Executive Committee of the MRC HTMR Network (and Hub Directors),
will describe the strategy and structure of the network, and highlight and illustrate its success with some of the
novel methodological innovations arising from this unique collaboration. The network’s success with capacity building and engagement with clinicians and trialists will be described, as well as the benefits and challenges of working in the trials community in the UK. Speakers will demonstrate how this knowledge can be adapted to support
27
improving trials on a global scale. Specific speakers and their topics include:
• Jane Blazeby – Strategic investment of a network and hubs in the UK
• Matthew Sydes – Guidance for working on trials: How small projects make big changes
• Paula Williamson – Outcome measures in trials: Adding value through a network approach
• Adrian Mander – Implementing novel trial designs
• Louise Bowman – Supporting capacity building: The future of trials methodology
The MRC HTMR Network is highly committed to capacity building in trials methodology, both nationally and internationally, and is successfully supporting the future of this important area of trials research.
http://www.methodologyhubs.mrc.ac.uk/
Speakers:
Chair:
Organizer:
Matthew Sydes, MRC Clinical Trials Unit, UK
Paula Williamson, University of Liverpool, UK
Adrian Mander, MRC Biostatistics Unit, UK
Louise Bowman, University of Oxford, UK
Paula Williamson, University of Liverpool
11:00 AM – 12:30 PMInvited Session 17: Guidance on Specifying the Target Difference (Effect Size) for
a RCT M, ST
Calculation of the number of participants needed (the sample size) is central to the validity of an RCT. This provides reassurance that the trial will identify a difference of a particular magnitude (target difference or “effect
size”) if such a difference exists. From both a scientific and ethical standpoint, selecting an appropriate target
difference is of crucial importance. However, determination of the size of difference that is “important” has been
neglected until relatively recently. A variety of approaches have been proposed and addressed by a large recent
review. However, there is a need for greater guidance to aid researchers and funders.
This session’s first speaker will consider sample sizes and target difference for clinical trials. The sample size
calculation is typically most sensitive to assumptions related to the target difference (effect size). In this practical
talk, case studies and examples from clinical trials will be used to illustrate how an effect size may be quantified
when designing a trial.
The second speaker will consider the challenge of defining an important difference in a patient-reported outcome.
Target effect sizes for patient-reported outcomes should ideally be the smallest that will make a difference to
patients or clinical practice, the so-called minimum important difference (MID). This talk will discuss the MID,
including how to estimate and use it. Following this, the third speaker will present findings from a review of target
differences used in trials and consider the effect sizes used in trials for different settings as well as how these
effect sizes were quantified.
The final speaker will present a personal view of developing trials as a chief investigator and co-investigator and
applying for funding to Canadian and U.S. funders. Attendees will be encouraged to express their views on existing research in this area and what is needed to further improve trial design.
Speakers:
Chair/Organizer:
Steven Julious, University of Sheffield, UK
Melanie Bell, University of Arizona
Joanne Rothwell, University of Sheffield, UK
Jonathan Cook, University of Oxford, UK
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11:00 AM – 12:30 PMInvited Session 18: Collaborating with Patient Advocacy Groups at the Design
Stage of Your Clinical Trial: Why It Is So Important TM
Engaging patient advocacy groups in the early stages of study design often appears daunting for the investigator.
There are perceived challenges related to identifying the right representatives that can share the patients’ perspectives and provide the necessary contributions to protocol development. Although challenging, this involvement can
be successfully achieved. This session will highlight successful collaborations between advocacy groups and clinical investigators and provide guidance on how to initiate the collaboration during the clinical trial planning process:
• Bray Patrick-Lake, director of stakeholder engagement for the Clinical Trials Transformation Initiative, will discuss
effective engagement with patient groups around clinical trials.
• Charles Mohan Jr., CEO and executive director of the United Mitochondrial Disease Foundation, will explain how
to identify and partner with the right advocacy group.
• David Schubert, vice president of Stealth Biotherapeutics, will provide industry’s perspective on conducting clinical research in collaboration with patient advocacy groups.
Discussant Erika Augustine will reflect on the three presentations and share her experience working with patient
advocacy groups of the NINDS-funded Parkinson’s Disease Network (NET-PD, NIH Exploratory Trials in Parkinson’s
Disease) and the Batten Disease Support and Research Association.
Speakers:
Discussant:
Chair:
Organizer:
Bray Patrick-Lake, Clinical Trials Transformation Initiative, Duke University
Charles Mohan Jr., United Mitochondrial Disease Foundation
David Schubert, Stealth Biotherapeutics
Erika Augustine, University of Rochester Medical Center
Valerie Durkalski, Medical University of South Carolina
Valerie Durkalski, Medical University of South Carolina
Charles Mohan Jr., United Mitochondrial Disease Foundation
11:00 AM – 12:30 PMInvited Session 19: Use of Mobile Health Technologies in
Pragmatic Clinical Trials TM, ST, E
Mobile devices have radically transformed many sectors of our society—including finance, business, retail, and
social communications—and offer considerable promise for similarly transforming health-care delivery models.
More than 90 percent of individuals worldwide have access to mobile devices, and mobile health interventions
have frequently been shown to produce outcomes comparable to or better than care delivered by clinicians. Further,
mobile health tools can be widely accessible, personalizable, and cost-effective.
This session brings together leaders in fields directly relevant to the use of mobile health technologies in pragmatic
clinical trials. Specifically, Lisa Marsch will review the state of the science of applying mobile health technologies to
a wide array of health behavior change interventions and the role that clinical trials research has played in this field
of scientific inquiry. Amar Das will then discuss the application of novel knowledge-driven computational methods
to support clinical research and pragmatic clinical trials. This overview will include a discussion of big data efforts
to extract information from electronic medical records and longitudinal data collected via mobile devices to support
trial recruitment and monitoring.
Tiffany Cvrkel will speak about ethics in the mobile era, such as obtaining consent, IRB review, and privacy-confidentiality issues. Carmen Rosa will moderate a discussion with the audience on opportunities, challenges, and future
directions in the use of mobile health technologies in pragmatic clinical trials.
Speakers:
Discussant:
Chair:
Organizer:
Lisa Marsch, Dartmouth College
Amar Das, Dartmouth College
Tiffany Cvrkel, UCLA
Carmen Rosa, NIDA
Carmen Rosa, NIDA
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11:00 AM – 12:30 PMInvited Session 20: Innovative Trial Designs for Precision Medicine ST
Recently, adaptive trial designs have drawn tremendous attention and interest in academia, industry, and government because of their potential to treat patients more ethically, improve the success rate of clinical trials, and
reduce the cost of drug development. Adaptive trial designs are indispensable for precision medicine because they
take into account individual variability in genes, environment, and lifestyle. Adaptive designs allow researchers to
make flexible clinical decisions based on patients’ characteristics and responses during clinical trials.
This session will cover innovative designs for Phase I, II, and III clinical trials in precision medicine. Specifically,
Alexia Iasonos will discuss the design and analysis of Phase I trials in the presence of patient heterogeneity; Ying
Yuan will present an innovative Phase II clinical trial with biomarker subgroups; Sumithra Mandrekar will review
several important designs, including basket, umbrella, and adaptive enrichment strategies, which are suitable for
Phase III trials; and Yu Shyr will discuss the statistical tasks for designing a clinical trial in the precision medicine
era.
Speakers:
Chair:
Organizer:
Alexia Iasonos, Memorial Sloan Kettering Cancer Center
Ying Yuan, MD Anderson Cancer Center
Sumithra Mandrekar, Mayo Clinic
Yu Shyr, Vanderbilt University
Haitao Pan, MD Anderson Cancer Center
Ying Yuan, MD Anderson Cancer Center
12:30 PM – 1:45 PM
Lunch/SCT Business Meeting
1:45 PM – 2:45 PM
Contributed Paper Session Time Slot III
CPS 13: Systematic Reviews and Meta Analysis ST, M
CPS 14: Novel Statistical Approaches to RCTs: Stratification, Global Outcomes,
Personalized Treatments and Mediation ST
CPS 15: Improving Participant Involvement in RCTs SC, DM
CPS 16: Electronic Data Capture and Data Visualization IS/DM, R
CPS 17: Compliance and Adherence ST
CPS 18: Multiplicity in RCTs ST
2:45 PM – 3:15 PM
3:15 PM – 4:45 PM
Invited Session Time Slot V
3:15 PM – 4:45 PM
Invited Session 21: Challenges of Implementing an Adaptive Design in an
Academic Network Setting ST, M, TM
Adaptive designs have initiated a paradigm shift in the world of clinical trials. Previously, investigators were
restricted to a fixed design, which left trials vulnerable to failure from ineffective treatments and incorrect
assumptions regarding treatment effect or variability as well as dose, duration, and/or population of interest.
Now funding agencies are requesting trials that are innovative, efficient, and able to answer more questions than
ever before. Designs abound in the literature that promise to deliver on these concerns, but implementation is
still a nascent undertaking with little available guidance.
This session highlights several lessons learned in the design and implementation of large-scale network-based
adaptive clinical trials. To ground the discussion, speakers will provide insight from a currently funded study
(ESETT) and several future studies implemented within the Neurological Emergency Treatment Trials (NETT)
and StrokeNet networks. The first talk will discuss how statistical modeling can be used to assist with planning
decisions beyond sample size including how to optimize drug supply and distribution, number of recruiting sites,
allocation ratios and imbalance methods to improve efficiency.
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The second talk will focus on the clinical aspects of adaptive trials including maintaining the blind while providing necessary information for continued care; striking a balance between answering multiple clinical questions
and design limitations arising from the clinical setting; and working with a clinical team unfamiliar with adaptive
designs. The third talk will discuss challenges of operationalizing both the statistical and clinical features of an
adaptive design, specifically considerations for developing a budget, selecting sites, operationalizing the protocol, and developing a meaningful informed consent document. A discussant will summarize the points and share
how the various stakeholders are collaborating to successfully build a portfolio of innovative adaptive designs in
an academic network.
Speakers:
Discussant:
Chair/Organizer:
Caitlyn Ellerbe, Medical University of South Carolina
Will Meurer, University of Michigan
Judith Spilker, University of Cincinnati
Renee Martin, Medical University of South Carolina
Caitlyn Ellerbe, Medical University of South Carolina
3:15 PM – 4:45 PM
Invited Session 22: Streamlining Clinical Trials: The Practicalities ST, TM, R
Randomized controlled trials are the cornerstone for reliably evaluating the safety and efficacy of therapeutic
strategies. For chronic conditions, where many treatments are expected to have only moderate effects, trials
need to be large in size and long in duration to achieve sufficient statistical power and ensure a robust result.
The regulations surrounding clinical trials are becoming increasingly burdensome and, as a result, the cost and
complexity of a standard approach to evaluating therapies is prohibitive (typically at least US$4-500M for large
clinical outcome trials). The development of potentially effective drugs is often stopped prematurely on financial
rather than scientific grounds, and academic trials of important scientific questions have become more difficult
to perform, resulting in a distortion of the scientific agenda.
It is widely recognized that the current system is unsustainable. Multi-stakeholder organizations such as the
Clinical Trials Transformation Initiative (CTTI, an FDA-Duke private partnership) are working hard to tackle key
obstacles, particularly in the area of regulation. In spite of these efforts, the uptake of streamlined approaches
to clinical trials remains limited. This may in part be due to ignorance of appropriate methodologies for streamlining, but perhaps is also a result of anxieties about acceptability from a regulatory viewpoint. There is a need for
clear illustrations of what is possible within the current regulatory framework.
This session will provide practical descriptions of approaches to streamlining clinical trials, using specific
examples of strategies that have been successfully adopted in a variety of settings. A series of presentations
will tackle each step of the clinical trials process, concluding with an account of how these methods have been
successfully applied within a U.S. context.
Given the current enthusiasm of the FDA and other regulatory agencies for promoting streamlined clinical trials,
it is anticipated that these illustrations will provide timely and sought-after guidance for trialists in a wide range
of disciplines.
Speakers:
Chair:
Organizer:
Trudie Lang, University of Oxford, UK
Martin Landray, University of Oxford, UK
Stephen Wiviott, Harvard University
John Alexander, Duke Clinical Research Institute
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3:15 PM – 4:45 PM
Invited Session 23: Statistical Challenges in Immuno-Oncology ST, M
The past several years have witnessed a resurgence of interest in cancer immunotherapy, owing to the clinical
success and regulatory approvals of several immune-targeted therapies and leading to the selection of “Cancer
Immunotherapy” as the 2013 Breakthrough of the Year by the journal Science. But statistical challenges exist
at all phases of clinical development. In Phase I immunotherapy trials, which assess safety and immunogenecity, there is no standardized metric to define whether a patient has achieved an immune response. In Phase II
immunotherapy trials, which assess efficacy, the proportion of patients who exhibit tumor shrinkage (termed the
objective response rate) and progression-free survival are commonly measured although these efficacy signals
are known to not be well-suited to immunotherapy.
In Phase III immunotherapy trials, which typically assess patient survival, the survival kinetics of treated patients
are different from those seen in chemotherapy trials. Delayed treatment effects of three to four months are often
observed. When comparing survival between treatments, this delayed separation in survival curves suggests that
the proportional hazards assumption has been violated. Moreover, group sequential designs for early termination
are problematic and futility testing is risky. In addition, a fraction of patients exhibit long-term survival and may
be cured, which impacts power. Given a mixture of patients, those who are cured and those who are not cured,
alternative analysis approaches such as mixture cure models should be considered.
These are a few of the statistical challenges that we face as the pace of cancer immunotherapy research accelerates across a wide spectrum of cancers. This session will include presentations on issues arising across all
phases of immuno-oncology clinical development. Katherine Panageas will describe her experience in early-phase
immunotherapy trials. Tai-Tsang Chen will focus on design and analysis issues in late-stage immunotherapy
trials. Michael LeBlanc will provide an overview of mixture cure models and discuss how such models may be
exploited for immunotherapy trials. Keavan Anderson will summarize the presentations and share his insights.
Clinical examples drawn from the oncology literature will be highlighted.
Speakers:
Discussant:
Chair/Organizer:
Katherine Panageas, Memorial Sloan Kettering
Tai-Tsang Chen, Bristol-Myers Squibb
Michael LeBlanc, Fred Hutchinson Cancer Research Center
Keaven Anderson, Merck
Rosemarie Mick, University of Pennsylvania
3:15 PM – 4:45 PM
Invited Session 24: Building the Clinical Trials
Enterprise of the Future IS/DM, ST, R
Health-care decisions regarding when and how to use medical products are best made when high-quality evidence
is available so the patient and clinician can weigh the benefits and risks of treatment. The most valid evidence
of a product’s effects is obtained from well-designed randomized, controlled trials (RCTs). Nevertheless, it is not
always clear that the populations studied in RCTs represent all those treated in clinical practice, nor is it feasible
to answer every question regarding the clinical uses of a product with an RCT.
Until recently, many experts felt there was an inevitable trade-off between internal validity and generalizability.
Recent deployment of electronic health records (EHR)—with the concomitant focus on common data standards
and terminology, the development of disease-specific and product-specific registries with high-quality data collection, and the proliferation of smartphones and mobile health apps—has created opportunities that could
overcome this perceived trade-off. We are approaching a tipping point at which a systematic approach can be
developed to integrate the clinical research enterprise with clinical practice through which observational data may
be leveraged to further enhance and streamline the conduct of RCTs. This new environment could be enabled by
the broader availability of real-world evidence derived from interactions within the health-care system, personal
data, and environmental data that exist in electronic form.
This session will focus on the use of real-world evidence to complement the data available from RCTs and to
32
enhance the conduct of these trials. It will provide an overview of the clinical trial enterprise as it exists today,
highlighting its successes and limitations. It will also feature a discussion of efforts to create a national resource
for evidence generation, including considerations such as interoperability of electronic health data management
systems and development of strategies to encourage efforts to build infrastructures to facilitate higher-quality
data collection and curation, including the use of data standards. Finally, it will offer a discussion of the experience of using real-world evidence for drug and device regulation.
Speakers:
Chair:
Organizer:
Robert Califf, FDA
Jonathan Jarow, FDA
Jeffrey Shuren, FDA
Robert Califf, FDA
Melissa Robb, FDA/CDER
3:15 PM – 4:45 PM
Invited Session 25: Prospective Individual Participant Data Meta-Analysis ST, M
Prospective Individual Participant Data Meta-Analysis (PMA) is becoming more common across all areas of healthrelated research. The Cochrane Handbook for Systematic Reviews of Interventions calls a PMA the “gold standard”
of systematic reviews. A prospective meta-analysis could arise spontaneously when a rapidly emerging question
with a high level of interest has multiple independent groups, possibly in different countries, considering similar
trials, or it could be planned in advance as a consortium of single center trials that are similar, but not identical.
This session aims to describe the advantages and disadvantages of a PMA compared with a multi-center RCT,
and the principles, methodology, and logistical issues in the design, conduct, and analysis of a PMA. Examples
of PMAs and lessons learned from the fields of family planning, obstetrics, and pediatrics will be presented.
Lisa Askie will explain why and how to use a prospectively planned meta-analysis. Elizabeth Thom will use the
example of starting an international collaborative effort in obstetrics to discuss the concept, planning, and initiation of a PMA. David Turok will talk about taking the leap to a new paradigm by providing notes on conducting a
first prospective meta-analysis. Finally, Lisa Askie will share lessons learned from a PMA collaboration of more
than thirteen years.
Speakers:
Chair:
Organizer:
Lisa Askie, University of Sydney, Australia
Elizabeth Thom, George Washington University
David Turok, University of Utah
Lynda Ugwu, George Washington University
Elizabeth Thom, George Washington University
Lynda Ugwu, George Washington University
4:45 PM – 6:00 PMPlenary Session: Trial of the Year:
The Learning Early about Peanut Allergy (LEAP) Trial
33
7:00 AM – 11:00 AM
Registration
8:00 AM – 9:00 AM
ounders Lecture - Richard Stephens
F
“Patients as Cancer Research - Walking the Walk in the UK”
9:00 AM – 9:15 AM
Break
9:15 AM – 10:45 AM
Invited Session Time Slot VI
9:15 AM – 10:45 AM
Invited Session 26: The International Behavioural Trials Network (IBTN):
An International Effort to Improve the Rigor and Impact of Behavioral Clinical
Trials TM
A rapidly growing, robust literature demonstrates that good health behaviors are associated with a reduction in
mortality and the prevalance of chronic noncommunicable disease. However, despite the great potential benefits
of health behavior interventions, the uptake and impact of existing behavioral interventions and the creation of
promising new interventions has generally been limited by methodological challenges specific to the design and
conduct of behavioral clinical trials. The International Behavioural Trials Network was created to address methodological issues unique to these trials and provide guidance on current best practices in the development and
implementation of behavioral trials.
This session will highlight some of the key issues unique to behavioral trials, detail novel approaches to resolve
these issues, and discuss some areas where further work is needed. Simon Bacon will review some of the key
work that has been done in the field of behavioral trials, such as the MRC’s complex intervention guidelines, the
theoretical domains framework, and the behavior change theory taxonomy. He will also identify some of the key
challenges in the delivery of behavioral trials, such as treatment fidelity and selection of the appropriate comparison group, and provide information on the structure and function of the International Behavioural Trials Network.
Susan Czajkowski will describe a framework—the ORBIT model—intended to accelerate the translation of findings from basic behavioral and social sciences research to the development of new behavioral treatments to
improve unhealthy behaviors. Features of the model will be described, as well as methods useful at each phase
and several examples of studies that are using the model.
Paul Montgomery will address the developmental process of the CONSORT Extension for Social and Psychological
Interventions, highlighting key additions to the main CONSORT statement for publishing trial data. In addition, the
development of behavioral trial specific GRADE guidelines and SPIRIT statements will be discussed.
Kenneth Freedland will describe appropriate frameworks to develop high-quality international behavioral trial networks and systematic processes by which global research targets can be identified and agreed upon. Examples
of how this has worked and failed in practice will also be discussed.
Speakers:
Organizer/Chair:
Simon Bacon, Concordia University, Canada
Susan Czajkowski, NIH/NHLBI
Paul Montgomery, University of Oxford, UK
Kenneth Freedland, Washington University, St. Louis
Simon Bacon, Concordia University, Canada
9:15 AM – 10:45 AM
Invited Session 27: FDA IND Reporting Final Rule Compels a New Dialog among
the DMC, Sponsor, and FDA ST, M, R
Concerns over product safety have resulted in late-stage program failures and market withdrawals. This has
focused more interest on aggregate safety analyses during clinical development. The FDA IND Reporting Final
Rule requires an expedited safety report whenever aggregate analysis indicates a clinically meaningful imbalance with an event occurring more frequently in the drug treatment group than in a concurrent or historic control
group. The FDA guidance on Safety Reporting Requirements for INDs and BA/BE Studies amplifies the Final Rule
in asserting that a systematic approach for safety surveillance “should include a process for reviewing, evaluatTrack Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM)
34
ing, and managing accumulating safety data from the entire clinical trial database at appropriate intervals.” All
of the available data, including data from outside of clinical trials, should be used to assess the safety of the
developing product. Any suspected adverse reactions should be evaluated relative to other events in ongoing
studies as well as previous studies.
DMCs evaluate accumulating unblinded data and make recommendations about the continuing safe conduct of
trials. Trial sponsors must decide how best to implement these recommendations to comply with IND reporting
and make the final decision on whether or not to stop a trial. However, while DMC recommendations are based
on differences observed between treatment arms, sponsors are generally blinded to these differences, adding
considerable uncertainty to the decision-making process. While DMCs should have unblinded access to all of
the available information, sponsors must conscientiously maintain their blind, so that together these two groups
can fully protect patients from unsafe treatments without compromising trial integrity or otherwise interfering with
the planned analyses.
Our goal is to formalize and improve conversations about safety signal monitoring and IND reporting among all
stakeholders in the conduct of randomized clinical trials. In particular, we will discuss blinded analyses of accumulating safety data for the Final Rule; DMCs and the Final Rule for safety reporting; and the role of the industry
sponsor and of external DMCs in aggregate safety analyses from pre-approval clinical trials.
Speakers:
Discussant: Chair: Organizer: Greg Ball, Merck
Janet Wittes, Statistics Collaborative
José Vega, Merck
Dave DeMets, University of Wisconsin
Amy Xia, Amgen
Greg Ball, Merck
Invited Session 28: Central IRBs: Implementation,
Effectiveness, and Optimization IS/DM, E
The regulatory requirement of Institutional Review Boards (IRBs) is to provide oversight of clinical trial research
to protect human subjects and ensure ethical research conduct. Local IRBs review research performed just at
their own site, while Central Institutional Review Boards (CIRBs) review research being conducted at multiple
sites. The Food and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) support the
use of CIRBs for multicenter trials with the goal of increasing efficiency, quality, and the speed of clinical trial
protocol approval. In addition, proposed changes to the Common Rule will require any U.S. institution engaged
in a cooperative study to rely upon a single IRB for that study, with some exceptions. This session will focus on
how CIRBs can be optimized and used effectively.
Using the example of the NINDS-funded Stroke Trial Network, Michael Linke will discuss the advantages and
disadvantages of using a CIRB; the resources required for establishing and administering one; the responsibilities, accountabilities, and liabilities between the local institution and the CIRB; and collaboration across multiple
CIRBs.
Robert Silbergleit will describe a project conducted by the Neurological Emergencies Treatment Trials (NETT)
network and the Pediatric Emergency Care Applied Research Network (PECARN) to explore, revise, test, and compare measures of local context review of community consultation activities for exception from informed consent
research by both local and central IRBs.
Catherine Dillon will focus on how clinical trial management systems can optimize CIRB operations by eliminating redundant or multiple software infrastructures, streamlining the reporting of safety events and unanticipated
problems, improving regulatory compliance, and acting as a central repository for all study-related information.
9:15 AM – 10:45 AM
Speakers:
Chair/Organizer: Michael Linke, University of Cincinnati/Cincinnati VA Medical Center
Robert Silbergleit, University of Michigan
Catherine Dillon
35
Invited Session 29: Use of Administrative and Registry Data in
Clinical Trials TM, IS/DM, E
Clinical trials, the gold standard by which health interventions are tested, are worth the investment. However, in
times of fiscal constraint, researchers may find greater efficiency by optimizing collaborations between traditional
epidemiological and clinical trial methodology. Such harmonized processes have been established in several
countries with a view to expediting advances in health-care delivery.
Are randomized registry trials the next disruptive technology in clinical research? In this session, Marc Jolicoeur
will describe the Canadian Randomized Registry Trial Initiative in Cardiology. Dean Fergusson will discuss pragmatic trials, comparing standards of care with simple protocols, consent, and data collection. Annette Hay will
outline opportunities and challenges associated with linkage of clinical trial and administrative data, including cancer patients’ preferences. Don Willison will offer a bioethical perspective, considering ethical issues in
registry-based pragmatic trials and data privacy. After these short presentations, Wendy Parulekar will facilitate
an open discussion.
9:15 AM – 10:45 AM
Speakers:
Discussant: Chair/Organizer: Marc Jolicoeur, Université de Montréal, Canada
Annette Hay, Queen’s University, Canada
Don Willison, Ontario Agency for Health Protection and Promotion, Canada
Wendy Parukelar, Canadian Cancer Trials Group, Canada
Annette Hay, Queen’s University, Canada
Invited Session 30: Crossover Trials: New Perspectives and Practical Implications
for an Efficient Design ST, M, E
For the assessment of a rapidly acting treatment whose benefit disappears quickly after discontinuation, the
crossover is an excellent trial design. Because each patient serves as his or her own control, crossover designs
typically yield efficient estimates of interventional effects. The last three years have yielded important methodologic findings regarding the design and analysis of crossover designs. This session will showcase research in
the areas of survival endpoints, the effective use of baseline measurements to increase efficiency, and adaptive
designs.
Mary Putt will briefly review the crossover design, and then our speakers will illustrate how these new statistical
methodologies can be translated into more effective clinical trials. Dean Follmann will first question the conventional wisdom that crossover designs are inappropriate for absorbing binary endpoints, such as death or HIV
infection. He will then explore the use of crossover designs in the context of non-repeatable binary endpoints
and show that, when there is heterogeneity in individual risk, the crossover design can be more efficient than
the more commonly used parallel group design
Next, Yuanyuan Liang will argue that ethical considerations compel us to balance the needs of patients with
the quest for balanced data and statistically efficient comparisons of treatment effects. She will propose a new
allocation rule for constructing response-adaptive crossover designs, one that is aimed at balancing estimation
precision and treatment benefit. She will illustrate how this new adaptive design can successfully allocate more
patients to better treatment sequences while sacrificing little in estimation precision.
Lastly, for the two-period, two-treatment (2×2) crossover trial, Devan Mehrotra will explore ways of incorporating
pretreatment baseline measurements (PTBMs) into estimation of the treatment effect. Here, the power to detect
a treatment effect reflects both the form of the variance-covariance matrix of the vector of responses, and the
approach to incorporating PTBMs into the analysis. His work illustrates significant problems with the change from
baseline analysis. Importantly, power gains are generally largest for an analysis of covariance approach that uses
the within-subject difference in treatment response as the dependent variable and the difference in PTMBs as
the covariate.
9:15 AM – 10:45 AM
36
Speakers:
Discussant: Chair/Organizer: Mary Putt, University of Pennsylvania
Dean Follmann, NIH/NIAID
Yuanyuan Liang, University of Texas Health Science Center at San Antonio
Devan Mehrotra, Merck
Susan Ellenberg, University of Pennsylvania
Mary Putt, University of Pennsylvania
10:45 AM – 11:00 AM
Break
11:00 AM – 12:30 PM
Contributed Paper Session Time Slot IV
CPS 19: Statistical Approaches in Stepped Wedge Designs ST
CPS 20: Statistical Issues in Cancer and Adaptive Trials ST
CPS 21: Trial Management & Study Coordination Across the Trial Lifecycle SC, DM
CPS 22: Managing Data in the 21st Century IS/DM, SC
CPS 23: Pragmatic Trials/Stepped Wedge/Missing Data ST
CPS 24: Regulatory and Ethical Issues in Trials R, E
2016 Program Committee
2016 Education Committee
Kaleab Abebe
Marianne Kearney Chase
Emily Van Meter Dressler
Caitlyn Ellerbe
Gustavo Jimenez-Maggiora
Ken Kobayashi
Beverly Koski
Todd MacKenzie
Graeme MacLennan
Sumithra J. Mandrekar
Kristine M. Nelson
Letitia H. Perdue
Rema Raman
Yves D. Rosenberg
Abigail Shoben
Rui Tang
Marc Walton
Amy Watson
Kevin Wilson
Wendy R. Parulekar
Domenic J. Reda
Kousick Biswas
Lynda Constable
Thomas Cook
Emily Van Meter Dressler
Dixie Ecklund
Suzanne Firrell
Virginia J. Howard
Qian Li
Leslie Ain McClure
Oscar Moreno
Yves D. Rosenberg
Wendy R. Parulekar
Domenic J. Reda
Chair: Li Chen
Co-Chair: Sumithra J. Mandrekar
Chair: Leslie Ain McClure
Co-Chair: William J. Meurer
37

Fairmont The Queen Elizabeth Montreal, Quebec

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