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Personalized medicine: Looking beyond the science

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Title: Personalized medicine: Looking beyond the science


1
Personalized 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

2
Ethical questions
  • Beyond the science
  • or
  • in the science?

3
Personalized 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).

4
Custom tailoring?
  • Will a custom tailored suit help US health care?

5
Challenges I
Measuring America 2008-2009 American Human
Development Project
6
Challenges II Percentage of children 6-16 years
old with iron deficiency by family income, United
States, 1988-94. (Source NHANES III, 1996)
7
Challenges III Percentage of children age 16 or
younger w/ food insufficiency by family income,
United States, 1988-94. (Source NHANES III,
1996)
8
Challenges 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)
9
Custom tailoring?
  • 2) Is personalized medicine a good tailor?

10
A 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

11
Personalized 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

12
CIGNA 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.

13
CIGNA 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

14
Use 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.

15
Use 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.

16
Diabetes 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

17
Extremely 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

18
What 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

19
Non-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

20
Non-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
21
What 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

22
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23
Where 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

24
We have our work cut out for us
Measuring America 2008-2009 American Human
Development Project
25
Is 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
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