Laboratory Medicine - Group for Research in Pathology Education

Abraham Flexner (1866-1959)
1910
“Although approximately
78% of medical schools
require coursework in
laboratory medicine, the
median time dedicated to
this topic is 12.5 hours,
not including exposure to
laboratory medicine
gained through clinical
rotations.” IOM Report 2015
Laboratory Medicine [aka, Clinical
Pathology (CP)] – An Often Neglected
Component of Medical School Curricula
“There’s no place
for pathology in
modern medical
curricula.”
Frank H. Wians, Jr., PhD, MASCP, MT(ASCP), DABCC, FACB
Editor-in-Chief, LABMEDICINE (2004-2011)
Professor, Department of Pathology
Paul L. Foster School of Medicine
Texas Tech University Health Sciences Center
Technical Director, Clinical Chemistry, University
Medical Center
El Paso, Texas
Professor of Pathology (1994-2009)
UT Southwestern Medical School at Dallas
1
Disclosures
The presenter has no current ties of any
kind to any of the companies cited during
this presentation.
From 1 Feb to 30 Aug 2015, the presenter
was a paid consultant to CompanionDx
Reference Laboratory, Houston, TX
2
Outline
How has laboratory medicine changed
between 1910 and 2015?
Medical school curricula:
 Where have we been?
 Where are we now
 Where are we going?
Proposal: A Case-Based Integrated Organ
System (CBIOS) Approach to Educating
Medical Students in Laboratory Medicine
Summary
3
How has laboratory medicine changed between 1910 and 2015?
 Availability of Direct Access (DAT) and Direct-to-Consumer (DTC)
Testing
 Number of laboratory tests has increased, and continues to increase, in
both number and complexity
 Emergence of new subspecialties (e.g., pharmacogenomics) with
increasingly challenging complex test reports to interpret.
 Analytical errors in laboratory medicine test results is the lowest of the
3 types of error affecting test results:
 Pre-analytical
 Analytical
 Post-analytical
 Emphasis on laboratory medicine training in medical school curricula
remains low.
4
From “Doc-in-a-Box” to “Lab-in-a-Box”
Give me a big lipid
panel with Glucola
and a large OGTT
Now offering DAT and
DTC laboratory tests
Robert Wachter, M.D.
5
DAT and DTC Testing Provide More Consultative Opportunities for Pathologists and
Doctoral-level Laboratory Medicine Specialists?
Note: Laboratories performing DAT/DTC are
subject to CLIA regulations!
Services not available in MD, NJ, NY and RI.
6
Distribution of Test Volume (~6 Billion) by Clinical or Anatomic Pathology Specialty in
CLIA-Certified High Complexity Laboratories (n = 172,000 in 2011)*
Summary (2011)
 ~6 billion laboratory tests
performed annually in ~172,000
high complexity labs (~72%) out
of the 239,000 labs in the U.S.
 AP tests represent ~10% of all
tests; CP (laboratory medicine)
tests represent the remaining
90%!
*Wians FH Jr, Gill GW. Lab Medicine. 2013;44:163-67.
7
Pharmacogenomics: An Emerging Global Subspecialty of Laboratory
Medicine
Page 1 of 14 page report!
8
Sources of Error in Stat Testing
 If the clinical laboratory is
provided with the:




Right specimen
At the right time
On the correct patient
With a complete and
accurate test request
 The laboratory will
provide a quality result in
a timely manner.
Carraro P, Plebani M. Clin Chem 2007;53:1338-1342.
9
Medical School Curricula
Where have we been?
Where are we now?
Where are we going?
10
Medical School Curriculum in 1910
 6 Categories (italicized)
evaluated:
1.
2.
3.
4.
Entrance requirement
Attendance
Teaching staff
Resources available for
maintenance
5. Laboratory facilities
6. Clinical facilities
Curriculum? Discussed in
general terms in the text:
11
Medical School Curricula
Where have we been?
Where are we now?
Where are we going?
12
Medical School Curriculum: Laboratory
Medicine – 1992-2014
1992*
2014**
120/126 (95%) medical school
respondents
 98/131 (75%) medical school respondents
 83 (69%) of which offered a total of 132
courses in laboratory medicine:
 Only 68 (57%) had required courses
 Most elective courses (53%) were in
general CP
 Courses offered in all 4 years of medical
school; majority (53%) in the 2nd year
 Lectures were the most common (39%)
teaching format out of ~75 h distributed
between lectures/labs/workshops
 Computer-assisted instruction used in only
10 schools (8%)
*Gottfried EL et al. Laboratory medicine education in United States
medical schools. Am J Clin Pathol 1993;100:594-598.
 82 (84%) of which offered some course work in
laboratory medicine:
 76 (78%) had required courses
 6% offered an elective course in laboratory medicine
 Courses offered in all 4 years of medical school;
majority (76%) in the 2nd year
 Lectures were the most common teaching form: 49% of
23.5 mean hours distributed between (mean hours):
◦ Lectures (11 h)
◦ Labs (5.6 h)
◦ Small group learning (6.1 h)
◦ Clinical consultations (0.1 h)
◦ Electronic/digital exercises (0.8 h)
 16 schools of the 76 with required courses in laboratory
medicine (21%) required digital or electronic learning
exercises
**Smith BR, et al. Laboratory medicine education at U.S. Medical Schools:
2014 Status Report. Online pre-publication from Academic Medicine.
A
13
A Tale of Two Medical Schools: Distribution of Pathology Course Hours (2015)*
*Excluding Exam hours. Note: Course titles were sufficiently similar between both medical schools to use the
nomenclature indicated on the x-axis of the chart above (inset identifies non-commutable course/topic titles).
14
UT Southwestern Medical School – No. of Lectures Dedicated to
Laboratory Medicine pre-2007 = 0; post 2007 = 4
Progress!
Judicious Use of the Clinical
Laboratory – II and – III added
after 2007
15
Medical School Curriculum: Traditional (Disciplinary-Based) vs Organ Systems-Based
Traditional Curriculum:
 Medical education
 Pathology
 Physiology
 Biochemistry
Organ Systems-Based Curriculum
16
Are there only 2 medical school curriculum approaches?
The only
approach
in 1910
Hecker K, Violato C. Fam Med. 2009;41(6):420-6.
Hecker K, Violato C. Teaching and Learning in Med.
2008;20(2):104-13.
17
Do Medical School Curricular Approaches Affect Competence in
Medicine?
“Various formal curricular
approaches have little differential
effect on students’ performance on the
USMLE.”
 Thus, while a curriculum is important,
the emphasis that so many medical
schools place on curriculum renewal
might be reconsidered. We reiterate the
statement made by Ripkey that “Overall
curricular approach may be less
important than the quality of the
curriculum implementation…”1 This
suggests that in medical education
reform there should be a shift from
curriculum restructuring to conducting
more meaningful research on areas such
as student characteristics, quality of
medical educators, and the proper use of
learning theory, educational theory,
assessment, and pedagogical techniques
on the student-teacher relationship in the
context of medical education.
i.e., Don’t focus on just the curriculum,
focus on the quality of medical students,
medical school educators, and other areas.
Mutifocal
approach
18
Medical School Curricula
Where have we been?
Where are we now?
Where are we going?
19
Predicting the Practice of Laboratory
Medicine in the 21st Century
Prediction*
 Comprehensive laboratory consultation
services
 Management of information technology
 Management of evidence-based disease
programs
 Direct patient access to laboratory services
 Emphasis on subspecialty practice
 One specialty: laboratory medicine (or
pathology). “The distinction between AP
and CP will disappear.”
*Burke MD, Am J Clin Pathol 2000;114:841-46.
My View of Reality (albeit after only
15 years into the new millennium)
 Generally offered by most laboratories, but often
underutilized
 Many laboratories have their own IT section to
manage their Laboratory Information System
(LIS) – better report formats and interpretive aid?
 Managerial training and interest limited for many
pathologists
 DAT (or DTC testing) approved by HHS via
CLIA amendment effective Feb 2014
 ABP alone offers specialty certification in 5
subspecialties of laboratory medicine*
 Distinction between AP and CP is alive and well.
 Where will we be within the next 85 years?
Greater emphasis on laboratory medicine
education and training?
DAT, direct access testing; DTC, direct-to-consumer testing
*Blood banking/transfusion medicine, chemical pathology, hematology,
medical microbiology, molecular genetics
20
More Evidence in Support of Increased Emphasis on Laboratory Medicine
Topics in Medical School Curricula
Is there any other medical specialty with such a
scope of influence on medical care in the U.S.?
From: Lewin Group: Laboratory Medicine: A National Status Report
21
Why should medical school curricula be revised to place a greater
emphasis on laboratory medicine training?
 Number and complexity of laboratory tests is
large and growing as new tests become available
in emerging subspecialties of laboratory medicine
(e.g., pharmacogenomics).

Thus, “the medical specialty that nearly every practicing
physician relies on every day, for which training in many
medical schools is limited to no more than a few lectures
scattered throughout the entire curriculum, is laboratory
medicine.”
Michael Laposata, MD
Over a 90 day period, Mayo Medical Labs added 56
new tests to their Test Directory of ~3,200 total tests
related to over 2,400 diseases, syndromes,
conditions, and infectious agents.
 ~90% of all laboratory tests (AP + CP) ordered
are laboratory medicine tests
 These tests are associated with 60-70% of all
critical decision-making such as:

Patient admittance

Discharge

Drug therapy
 Without sufficient knowledge of laboratory tests,
health care providers are more prone to:

Inappropriate test ordering

Mistakes in interpreting test results (i.e., what do the
results mean?)

Poor case management

Increased costs per patient

Adverse outcomes (Jennifer Rufer case)
2.5
22
What do the test results mean?
Of interest to many, as this paper has been the
most viewed on the ASCP website since its
publication in 2009
23
One Approach to Accurate
Interpretation of Laboratory
Test Results: More Informative
Lab Reports
As laboratory tests become
more complex with
multiple variables,
clinicians will need
assistance with rapid and
accurate interpretation of
test results, including lab
reports containing the
results of any calculations
and formatted, preferably,
on a single page that
provides the interpretation,
along with any other useful
information to improve
patient care and outcomes.
Important:
Countersigned
by an M.D.
Wians FH Jr. Lab Med 2009;40:5-12.
24
Examples of Lab Reports That Distill Complex Laboratory Test Results to a 1-Page Interpretive Report
Based on Collaboration Between Laboratory Medicine and Physician Specialists
Descriptive info –
interpretation left
to neurosurgeon
Without such a report, how does a clinician interpret 27
ACTH and 3 cortisol results from 3 sites over 9 time points?
Wians FH Jr. Lab Med 2009;40:5-12.
25
Do we need change in medical school curricula?
 Greed is NOT good –
change is good and
inevitable!
 What should change
look like in medical
school curricula of the
21st century?
Charles Darwin (1809 – 1881)
“It is not the
strongest of the
species that
survive, nor is it
the most intelligent,
but rather, it is the
one most adaptable
to change.”
26
Should Some of the Curriculum Content for Improving Pathology Resident Competency in
Laboratory Medicine Be Incorporated Into Medical School Pathology Training? Why?
 Core competencies
 Patient care
 Medical knowledge
 Practice-based learning and improvement
 Interpersonal and communication skills
 Professionalism
 Systems-based practice
 Taught using a combination of didactic
methods (e.g., case studies/discussions)
and subspecialty-based rotations.
 After medical school, not all medical
students choose pathology as their
residency specialty and many of the
topics proposed as appropriate for
pathology resident competency are
equally as appropriate for clinicians in
any specialty who order laboratory tests.
27
Do Medical School Curricular Approaches Affect Competence in
Laboratory Medicine? Results of a CAPSTONE Course.
Source: Molinaro RJ. Arch Pathol Lab Med. 2012;136:1423-1429.
Results of Medical Student (n = 84) Performance Pre- and Post Medical School
Clinical Laboratory Experience (MSCLE) Quizzes
Lab Medicine Topic
Statistically
P Value
significant
(Pre- vs Post-MSCLE Quiz Scores) (@ α = 0.05)?
Test panels
0.001
Yes
Proper blood draw
0.001
Yes
Test interpretation
0.01
Yes
Preanalytical variables
0.13
No
Diagnostic specificity
0.16
No
Reference intervals
0.54
No
Assay standardization
0.62
No
Test validation
0.81
No
Point-of-care testing
0.82
No
Critical values
0.99
No
Overall (n = 84 med students)
0.002
Yes
Overall statistical significance after only 1.5
days of MSCLE! What would happen in a
larger study of 3 or 15 days of MSCLE or
comparing medical student performance
on the USMLE between those without a
MSCLE versus those with a MSCLE?
28
The Case For Case Studies
All case study
examples that
follow were
written, as first
author, by either
pathology residents
or 2nd-year medical
students doing a
pathology rotation!
29
The Case for Case Studies
Sample Case Study from the journal, LABMEDICINE
 Format standardized
 Emphasis on accuracy-brevity-clarity
(the abc’s of effective writing).
Sample case study consists of only 5
pages.
 Questions standardized with focus on
combining the patient’s clinical
information:
 CC
 HPI
 PMHx
 FHx
 PE
with the principal laboratory findings
to arrive at the most likely diagnosis
based on explaining the patient’s
most striking laboratory findings.
 Easy to read, digest, and remember
key findings
30
Proposal: A Case-Based Integrated Organ System (CBIOS) Approach to
Educating Medical Students in Laboratory Medicine
AP
31
How the design of standardized case study questions promote clinical and
laboratory medicine reasoning skills and medical knowledge simultaneously
Standardized Case Study
Questions
Learning Objective Satisfied
1. Clinical reasoning that includes BOTH clinical and
laboratory medicine findings (and imaging studies, etc.)
2. Pathology, pathophysiology, differential diagnoses
3. Clinical reasoning
4. Clinical reasoning based on combining clinical and
laboratory medicine information
5. Clinical reasoning
6. Pathology, pathophysiology
7. Clinical reasoning
8. Medical knowledge, laboratory medicine reasoning
9. The ability to synthesize clinical and laboratory medicine
information
10. Pathology, pharmacology
11. Pharmacology, pharmacokinetics, laboratory medicine
12. Pathophysiology, pharmacology
13. Clinical reasoning, pharmacology
14. Medical knowledge, biostatistics, epidemiology
15. Medical knowledge, biostatistics, epidemiology
32
The Link Between Clinical Reasoning and Laboratory Medicine:
Recommendations from the Sep 2015 IOM Report
 As part of this cognitive process,
clinicians order laboratory tests in ~30%
of primary care visits and:
 Uncertainty about the tests ordered occurs ~15% of
the time
 Confusion about interpreting the results occurs in
~8% of the cases in which tests were ordered.
 Sources of error in diagnostic testing
include incorrect test ordering or correct
test ordering, but with incorrect
interpretation (Jennifer Rufer case)
 Thus, the IOM report
recommends that medical
educators focus on improving
performance in several areas,
including:
 Appropriate use of diagnostic tests
and the application of these results on
subsequent decision-making
33
An interesting medical student survey?
 If medical students* in multiple medical schools in
the U.S. were surveyed on which teaching format
they preferred among the following choices:
a) Traditional 2+2
b) Organ-system based approach
c) Case-based integrated organ system approach (CBIOS)
d) Other (specify)
what would be the outcome? At the peril of predicting the
future, my bet is CBIOS.
* And graduates whose years of graduation span the time period over which different medical student
teaching approaches were used.
34
Example of a Skill Level 1 Medical Knowledge Goal in Clinical
Immunology Laboratory Testing Applicable to All Clinicians?
Understand and know how to evaluate,
prevent, and correct for immunologic
interferences associated with
immunoassays, including the following:
 Human anti-mouse antibodies (HAMAs)
 Rheumatoid factors
 Heterophilic antibodies reacting with
immunoglobulins from multiple species
 Autoantibodies to measured substances
 Cryoglobulins and cold agglutinins
Smith BR, et al. Amer J Clin Pathol. 2006;125(Suppl 1):S3-S37.
35
Why Medical School Pathology Courses Should Include Discussion of HAMA and Other
Types of Immunoassay Interferents
 HAMA are the most common type
of human anti-animal antibodies

Prevalence varies widely (<1% to 80%)
 Heterophilic antibodies occur in
patients’ sera related to a variety of
diseases, for example:


Rheumatic fever
Selective IgA deficiency (prevalence
varies by population; ~1/223 to 1/1000
people)
 “Interference in immunoassays
may lead to “misinterpretation of a
[sic]” (erroneous) patient’s results
(reported) by the laboratory and
the wrong course of treatment
being given by the physician.”
AK Knight (see left panel)
36
Incorporation of Smith et al. Skill Level 1 Clinical Immunology Knowledge Objectives into
a HAMA Lecture to Pathology Residents at UT Southwestern Medical Center
 Outline of Lecture on HAMA
Interference in Immunoassay Tests:
A Case Study Example of HAMA Interference
 What are they?
 How do they differ from heterophile Ab’s?
 What are the causes of HAMA?
 Why all the interest in HAMA?
 What effects can HAMA cause in
immunoassays for various analytes?
 How important is HAMA interference in
immunoassays?
 What are the immunological characteristics
of HAMA?
 What are the consequences of HAMA in
patient’s samples?
 What are the mechanisms of HAMA
interference in immunoassays?
 How do you establish or eliminate HAMA
interference in immunoassay testing?
37
The Jennifer Rufer Case
 22 y.o., recently married, using
contraceptives, presented with irregular
bleeding between menstrual periods
 Serum hCG concentration was elevated
 Ultrasound showed no fetal sac
 Worked up for ectopic pregnancy
38
History Continued
 Laparoscopy was negative for
ectopic pregnancy
 Dilatation and currettage
(D&C) performed with
histopathology indicating the
presence of only normal
menstrual tissue
 July 1998: [hCG] still elevated trophoblastic choriocarcinoma
suspected
 Chemotherapy administered
with no effect on [hCG] (i.e.,
remained elevated)
 Hysterectomy performed
with no pathological
abnormalities noted
 Rare, resistant (to ChemoRx)
form of choriocarcinoma
suspected with possible
metastasis to extrauterine
location
 Attending physician became
suspicious about persistently
elevated [hCG]
 Patient’s serum sample sent
to 2 referral labs for hCG
testing
 Both referral labs used the
same hCG immunoassay as
the initial lab! hCG results
elevated.
39
History Continued
More chemotherapy administered
using 5 chemotherapeutic agents
CT scan performed which demonstrated a
suspicious lung nodule
Lung lobectomy performed
40
History Continued
 Finally, the validity of the
hCG results was
questioned after a total of
>45 hCG determinations
had been performed on the
patient’s serum during the
course of her treatment
 Patient’s persistently
elevated hCG levels
attributed to false-positive
test results due to HAMA
interference
Presumably, there was no consultation
with clinical pathology staff? Why?
 Patient underwent:




D&C
Hysterectomy
A round of initial ChemRx
A second, more aggressive,
round of ChemoRx
 Lung lobectomy
due, in part, to FP hCG results
and unrecognized HAMA
interference
 Total lawsuit $ award:
$16.2 million!
 13 additional lawsuits
filed – current status
unknown
41
Final Thoughts
- Abraham Flexner, 1910
 Imagine a medical school pathology course with BOTH a CP and AP component
organized around 11 case studies.

One case related to each of the 11 organ systems focused on prevalent and significant diseases
associated with one or more of the organs comprising the organ system, followed by class
discussion of the case study selected using a standardized set of questions in a studentmoderator interactive format.

The standardized questions cover all of the components of the IOM Diagnostic Testing
roadmap.
 The goal of CBIOS is to provide medical students with a strong “introduction” to
laboratory medicine that will complement their exposure to real-world laboratory
medicine during their clinical years.
42
Thank You For Your Attention!
“Hopefully,” this will not be the curriculum of medical schools
in the 21st century!
“In conclusion, both clinical necessity and the medical education literature suugest
that pathology does have a place in modern curricula. The position of pathology may
be precarious, but is prospects are promising”
43