Improving Genetic Test Reporting Practices

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Improving Genetic Test Reporting Practices (A
Clinical and Laboratory Setting Perspective with
implications for patients and their families)
Laboratory
Doctor's Office
Ira M. Lubin, PhD, FACMG Geneticist Division of
Laboratory Systems Centers for Disease Control
and Prevention
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What is wrong with this Picture?

• A 25-year-old pregnant woman was referred for
  CF testing
• by her OB-GYN.
• As for a previous pregnancy, she was found to
  carry one
• copy of a cystic fibrosis associated mutation
• Her response was "This is no big deal - I have
  the exact
• same thing happen to me in my last pregnancy"

STILL AT RISK!
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Or this?

• Born _at_ 32 weeks in March 2004
• family history of heart disease
• Transferred 60 mi to NICU 4 week stay
• Two episodes of bradycardia, hypotonia, and
  cyanosis in first 10 days of life
• ECG QTc 420 msec borderline
• Neuroultrasound / Metabolic workup
• Ped Cardiologist possible Long QT Syndrome
  (LQT)
• Mutation testing for LQTS NEGATIVE - LQTS RULED
  OUT
• REEVALUATION by 2nd pediatrician - LQT SYNDROME
  DIAGNOSED

Diagnosed in Patient and other family
memebers POTENTIALLY SAVED THREE LIVES!
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Our Question and Task
How can we help make DNA-based molecular
genetic laboratory test reporting most useful to
clinicians who are not geneticists?
Report genetic test results in a manner that
clearly emphasizes the clinically important
principles
THREE COMPONENTS
Family History/ Implications
Future health Implications
Penetrance/Expressivity
Residual Risk
Counseling
Options?
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What happens when a test is ordered?
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What happens when a test is ordered?
Experience
Training
Test Order
Interpretation
influenced by 1) Result 2) Available patient
info 3) Methodology 4) Expertise 5) Policies
Test Report
Practice Policies
Information Resources
What is communicated?
What should be communicated?
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Our Premise as Presented from the World of
Business
"We have more information now than we can use,
and less knowledge and understanding than we
need. Indeed, we seem to collect information
because we have the ability to do so, but we are
so busy collecting it that we haven't devised
means of using it" from Warren Bennis
distinguished professor of business
administration and founding chairman of the
Leadership Institute at the University of
Southern California's Marshall School of Business
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What's Missing?
WHAT IS CLINICALLY RELEVANT, ACTIONABLE, AND
IMPORTANT FOR MY PATIENT TO KNOW? HOW CAN THE
LAB GET ME THE INFORMATION THAT THEY HAVE THAT I
NEED?
WHY ARE YOU ORDERING THIS TEST? PLEASE SUPPLY
APPROPRIATE PATIENT AND FAMILY INFORMATION
THE CATCH THE INTERPRETATON OF A GENOTYPIC
RESULT IS NOT SELF EVIDENT - IT DEPENDS ON OTHER
FACTORS
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An Example
A 25 year old woman is very concerned about a
genetic predisposition to breast cancer and
wishes to be tested. She reports that her 72
year old grandmother was recently diagnosed but
has no other information.
Should she be tested?
In the absence of other indications, most likely
result is no finding
But what if a sequence variation of unknown
significance is found?
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The laboratory is challenged with reporting the
results in context?
"The Patient is postive for the 1706A in the
BRCA1 Gene"
A DNA-based test result alone does not define
it's clinical significance Other factors having
a role 1. Clinical Presentation
(Symptoms) 2. Family History 3.
Race/Ethnicity 4. What the test measures (What
mutations are tested?) 5. If a sequence
variation was found, what is known about its
association with the medical condition?
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How broad is this issue? Public Health
Implications?
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Therefore, we return to this
WHAT IS CLINICALLY RELEVANT, ACTIONABLE, AND
IMPORTANT FOR MY PATIENT TO KNOW? HOW CAN THE
LAB GET ME THE INFORMATION THAT THEY HAVE THAT I
NEED?
WHY ARE YOU ORDERING THIS TEST? PLEASE SUPPLY
APPROPRIATE PATIENT AND FAMILY INFORMATION
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Our Approach Implementing a Common Language in
Communicating Concepts
Teamwork and Community Participation is Vital for
Success
Consumers
Health Care Managers
Clinicians
laboratories
Policy Makers
Payers
Educators
Information Specialists
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Our Approach Implementing a Common Language in
Communicating Concepts
1. ASSESS CLINICAL AND LABORATORY PRACTICES TO
DETERMINE BASELINES (Have primarily focused on
DNA-Based Cystic Fibrosis as a model) -
Published studies (Genet Med (2002) 4324, Genet
Med (2003) 5166) - 2003 and 2005 workgroups
(http//www.phppo.cdc.gov/dls/genetics/comm0520
03.aspx) - Clinician and Laboratory Surveys 2.
ASK CLINICIANS 1. WHAT IS CLINICALLY
RELEVANT? 2. HOW DO THEY WISH LABORATORY
RESULTS COMMUNICATED? 3. FACILITATE
INTERACTIONS AMONG LABORATORY AND CLINICAL
SETTINGS AND RESOURCES TO DEVELOP AND TEST PILOT
PROCESSES.
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The Approach Implementing a Common Language in
Communicating Concepts Some Findings
1. Guidelines provide elements for inclusion
within reports and provide some model reports
but fail to adequately address how concepts
(i.e., risk) can be effectively communicated 2.
Test ordering and reporting practices are highly
variable in terms of the information requested
and returned 3. Multiple persons are
responsible for various aspects of the patient's
healthcare. 4. Physicians (within our study
groups) tell us that reports are relatively
unsatisfactory in how the interpretive component
is presented. 5. PRACTICE SETTINGS ARE CHANGING
- availability and use by non-specialists
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Reporting a Diagnostic Result
Patient Bobby 384910kb CgtT finding clinical
symptoms of CF
Format 1 "The patient is at least a carrier of
CF consistent with being unaffected. However,
a second mutation cannot be ruled out." Format
2 "The patient has been identified as a CF
carrier" Format 3 "One CF mutation was
identified. This result does not exclude a
diagnosis of CF"
Key Principle Uncertainty about second mutation
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Reporting a Carrier Test Result
Cystic Fibrosis Carrier Testing / no mutations
found, /- fam. hx
Format 1 "Based on the pedigree provided, the
patient has a risk of xx. Risk is reduced by
xx by this test resulting in a residual risk of
xx based on her reported ethnicity." Format
2 "There is no detectable CFTR gene mutation,
decreasing the probability of being a
carrier"..........."An expanded mutation panel is
available. Format 3 "Based on this result,
there is not a high risk for having a child
affected with CF.
Key Principle Uncertainty about undetected
mutation and relevance to residual risk
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The Genetic Testing Process is a Team Approach
Activities Assessed
Filling out / reviewing test requisitions Reviewin
g genetic test results Communicating genetic test
results to patients Recommending follow up testing
Who is Responsible?
What are the implications for ordering
and reporting genetic tests and results?
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What's Next?
1. We want to ask clinicians (non-geneticists)
about how genetic test results can be effectively
communicated in the form of the written report
and what supportive resources are needed. -
Clinician workgroups (3-4 workgroups)
2. Bring together "the community" to evaluate
and integrate workgroup findings to develop,
pilot, and evaluate model reports and supportive
educational and informational resources.
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Closing Questions
How can we input your experiences into this
process?
How would you ultimately measure our success?
Other questions?