Thoughts about Personalized Medicine and Comparative Effectiveness Research

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Thoughts about Personalized Medicine and
Comparative Effectiveness Research

• Michael S Lauer, MD, FACC, FAHA
• Director, Division of Cardiovascular Sciences
• NHLBI/NIH
• October 28, 2009
• Disclosure Not views of NHLBI/NIH/HHS

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A Popular, Prestigious, and Logical Therapy
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pload.wikimedia.org/wikipedia/commons/0/01/Blood_l
etting.jpg
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A Government Run Clinical Trial
It had been so arranged, that this number was
admitted, alternately, in such a manner that each
of us had one third of the whole. The sick were
indiscriminately received, and were attended as
nearly as possible with the same care and
accommodated with the same comforts. Neither Mr
Anderson nor I ever once employed the lancet. He
lost two, I four cases whilst out of the other
third treated with bloodletting by the third
surgeon thirty five patients died.
Milne I and Chalmers I. J Epidemiol Community
Health 2002561a
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Modern Examples of Bloodletting

• Thalidomide (birth defects)
• Hormone replacement (cancer, strokes)
• Oxygen for premature infants (blindness)
• Anti-arrhythmic drugs (higher death rate)
• Bone marrow transplantation for breast cancer
  (higher death rate)
• PSA for prostate cancer (over-diagnosis)

Thank you to Andrew Epstein
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AMI and the Occluded Coronary Artery
http//www.circulation.or.kr/info/case/200904/fig1
.gif http//www.indiastudychannel.com/attachments
/Resources/82666-221135-Coronary20Angiogram.jpg
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Predictive Observations and Logic Open It!
NHLBI Lamas GA et al. Circulation
1995921101-9
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Physician Bias and Ethics

• When researchers tried to organize a randomized
  study of the benefits of angioplasty for patients
  who had suffered a heart attack three days or
  more before, they ran into a problem. Many
  doctors were so convinced of the value of this
  procedurethat they thought it would be unethical
  to assign any patients to the control group,
  which would get all the best medicines for this
  condition but not the artery-reopening procedure.
• But the researchers persisted, with heavy support
  from the National Heart, Lung, and Blood
  Institute. After four years of work examining
  2,166 patients, they came to an unexpected
  conclusion.

Boston Globe, December 9, 2006
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Experiment Counter to Logic and Observations
Hochman JS. N Engl J Med 20063552395-407
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Threads (Remember HRT?...)

• Logic, belief, personality, hope, (and hype)
• Excessive reliance on observational data
• Real conflicts of interest

N Engl J Med 19993401801-1811
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What About Pharmaco-genomics?
Sub-groups and Interactions
Carriers of KIF6 Variant Non-carriers of
KIF6 Variant
Iakoubova OA. J Am Coll Cardiol 200851449-55
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A Rigorous Approach COAG Trial
Eligibility Patients with gt 3 months indication
for warfarin therapy
Randomize 11, N 1,238
Rapid (lt 24 hours) Genotyping for 2C9 and VKORC 1
Genotypes
Pharmaco-Genomic Strategy
Clinical Strategy
Outcomes
Outcomes
http//coagstudy.org/
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Why is CER a Lightening-Rod?
Whats the objection? Scientific medicine has
always been based on conducting well designed
research to determine what works. The problem is
that comparative studies will be threatening to
makers and sellers of costly goods and services
that offer no benefit over existing
alternatives.
Avorn J. N Engl J Med 20093601927-9
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Final Thoughts

• Personalized medicine pharmaco-genomics
• Intriguing hypothesis
• Logic and observations are inadequate
• Prediction is not the same as prevention
• Randomized trials are the key
• Subset analyses provide clues
• Gold standard randomize on the approach
• Scientific, political, and economic discipline