Title: Personalized medicine: Looking beyond the science
1Personalized medicine Looking beyond the science
- Pamela Sankar, PhD
- Department of Medical Ethics
- University of Pennsylvania
- AAAS-FDLI Personalized Medicine Planning for the
Future Colloquium I Diagnostics and Diagnoses
Paths to Personalized Medicine June 1-2, 2009
Washington, DC
2Ethical questions
- Beyond the science
- or
- in the science?
3Personalized medicine as High end shopping
- In the same way you can walk into a high end
clothing store and be fitted for a
custom-tailored suit, you may soon have the
opportunity to go to your doctor's office and
receive a custom-tailored treatment for your
ailments. - www.deloitte.com/dtt/article (accessed 2009 Jan
28).
4Custom tailoring?
- Will a custom tailored suit help US health care?
5Challenges I
Measuring America 2008-2009 American Human
Development Project
6Challenges II Percentage of children 6-16 years
old with iron deficiency by family income, United
States, 1988-94. (Source NHANES III, 1996)
7Challenges III Percentage of children age 16 or
younger w/ food insufficiency by family income,
United States, 1988-94. (Source NHANES III,
1996)
8Challenges IV - Percentage of children 1-5 years
old with blood lead levels 10 ug/dl by family
income, United States, 1991-94. (Source NHANES
III, 1996)
9Custom tailoring?
- 2) Is personalized medicine a good tailor?
10A custom tailored suit should fit, but does this
one?
- The most important thing about a treatment is
that it is effective, - not merely that it ought to be
effective. - R. Asher, 1961 Lancet
11Personalized medicineThe future is now
- By 2010 predictive genetic tests will be
available for as many as a dozen common
conditions - Francis Collins, July 2005
- Personalized medicine is not a promise of the
future it is fast emerging as the current state
in diagnosticstherapeutics Deloitte 01.27.09
12CIGNA Coverage Policy
- Subject Drug Metabolizing Enzyme Genotyping
Systems (AmpliChip, Invader) Effective
Date..........................12/15/2008 - The specific enzymes that are analyzed by this
test play a role in the metabolism of about 25
of all prescription drugs, including
antidepressants, antipsychotics, beta-blockers,
and some chemotherapy drugs. AmpliChip laboratory
test system as designed may allow physicians to
consider unique genetic information from a
patient when selecting medication and doses of
medication for a variety of common conditions
such as cardiac disease, psychiatric disease, and
cancer.
13CIGNA Coverage Policy
- CIGNA does not cover Drug
- Metabolizing Enzyme Genotyping
- Systems (e.g., AmpliChip
- CytochromeP450 Genotyping
- Test Invader UGT1A1 Molecular
- Assay because they are considered
- experimental, investigational or
- unproven. 12.15.2008
-
14Use of genetic testing to guide the initiation of
warfarin therapy
- California Technology Assessment Forum 12/15/2008
- TA Criterion 3 The technology must improve net
health outcomes. - TA Criterion 3 is not met.
- TA Criterion 4 The technology must be as
beneficial as any established alternatives. - TA Criterion 4 is not met.
- TA Criterion 5 The improvement must be
attainable outside of the investigational
setting. - TA Criterion 5 is not met.
15Use of genetic testing to guide the initiation of
warfarin therapy
- California Technology Assessment Forum 12/15/2008
- Conclusion
- the use of genetic testing to guide initial
warfarin dosing does not meet Technology
Assessment Criteria 3 through 5 for safety,
effectiveness and improvement in health outcomes.
16Diabetes and ARMD Off the rack will have to do
- Diabetes
- As compared with clinical risk factors alone,
common genetic variants associated with the risk
of diabetes had a small effect on the ability to
predict the future development of type 2
diabetes. The value of genetic factors increased
with an increasing duration of follow-up.
Lyssenko NEJM 2008 - A genotype score based on 18 risk alleles
predicted new cases of diabetes in the community
but provided only a slightly better prediction of
risk than knowledge of common risk factors alone.
Meigs NEJM 2008 - Age-related macular degeneration
- ...although genotype can identifyindividuals
with extreme risk or extreme protection the
majority of the population inherits some of each
category, resulting in the lifetime risk of AMD
that is only modestly different from the overall
population average. Maller 2006
17Extremely complicated
- "Pharmacogenomics, which from my perspective
has been one of the most promising areas of
personalized medicine, has also turned out to be
extremely complicated, not that we shouldn't have
known that. - Francis Collins, former director of NHGRI,
- Personalized Medicine Coalition Meeting
- January 30, 2009
18What we should have known one size does not fit
all
- Environment
- One size does not fit all applies
- not only to traditional drugs but
- also to challenge of accurately
- modeling the environment of
- different subjects
19Non-genetic factors drug response
- Environmental influences
- Diet alcohol intake
- Cigarette smoking
- Diseases
- Liver and kidney diseases which effect
metabolism - Interaction with other drugs
- Patient compliance
20Non-genetic factors disease
- Geographic Location
- Housing Conditions
- Occupational Risks
- Access to Services
Environmental Influences
- Social Class
- Age
- Gender
- Ethnicity
Social Structure
- Smoking
- Nutrition
- Physical Activity
- Psychosocial Factors
Lifestyle Influences
- Blood Pressure
- Cholesterol
- Obesity
Physiological Influences
Source McKinlay J, AJPH 1999
21What we should have known one size does not fit
all
- Genotype-phenotype relationship
- Understood only imperfectly and
- becomes more complex as more is learned
- about factors such as
- relations among genes
- relations between the human genome and the human
microbiome - features such as copy number variation
- epigenetic modifications
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23Where is heritable risk hiding?
- Alleles with small size effects
- Rare variants
- Population differences
- Epistatic interactions (where combined risk is
greater (or lesser) than the sum of the risk form
individual genes) - Copy number variation
- Epigenetic inheritance (chemical modifications of
DNA that can alter the expression of genes --and
thus physical traits--without changing the
sequence) - D. MacArthur GeneticFuture, Blog 2008
24We have our work cut out for us
Measuring America 2008-2009 American Human
Development Project
25Is custom tailoring the best answer?
- As long as there are cold and nakedness in the
land around you, - so long can there be no question at all but
that splendor of dress is a crime. - John Ruskin