ETHICAL ISSUES IN

PERSONALIZED MEDICINE

Mark A. Rothstein, J.D.

Herbert F. Boehl Chair of Law and Medicine
Director, Institute for Bioethics, Health Policy and Law
University of Louisville School of Medicine
A. Research Ethics
B. Access Issues
C. Race and Ethnicity
D. Personalized Medicine and Privacy
A. Research Ethics

1. Biobanks

• Consent / authorization
• Confidentiality
• Intellectual property
• Benefit sharing
 2. Selecting drug targets
• Demographic profiles
R & D for new pharmaceuticals costs millions
(sometimes tens or even hundreds of millions
of dollars).
Before committing these resources, any
biotech or pharma company would want
to know whether they could expect to
recoup those costs – and to do that they
would need to know the demographic
profile of people with the genotype of
interest.
 • Orphan genotypes

A related issue is simply the number of

individuals with a certain genotype.
If it’s sufficiently rare, then it would not
be cost-effective to develop meds
specifically targeted for this group.
The Orphan Drug Act of 1983 defines
an “orphan drug” as one affecting
fewer than 200,000 persons in the
U.S., and it gives incentives (e.g., tax
incentives) to companies to develop
drugs for these diseases.
Should there be comparable legislation
for “orphan genotypes”?
B. Access Issues
1. Health disparities
Pharmacogenomics, by definition, means
spending (at least at the R & D stage, and
perhaps much longer) more health care
resources on one or more segments of the
population.
• Is it ethical to do so when much of the world
lacks basic sanitation, immunization, and
“common” medications?
• Is it ethical to do so when nearly 50 million
Americans are uninsured?
• Could pharmacogenmics increase overall
spending on drugs to the point where more
people will actually become uninsured?
2. Payment systems
How will payers decide whether to cover
pharmacogenomic-based medications?

• Diagnosis and prognosis

• Relative safety, efficacy, and cost
Will pharmacogenomics lead to
increased stratification or “tiering”
of health care in the U.S. between
private and public payers and
based on the nature of an
individual’s health insurance?
C. Clinical Issues
1. Burdens on the health care system

• Education and continuing education

for physicians, nurses, pharmacists,
et al.
• More genetic testing, more genetic
counseling, more patient education
• Who has the time? Who will pay?
 2. Pressures for adoption of
pharmacogenomics

• Liability avoidance
• Patient demand (including DTC advertising)
D. Race and Ethnicity

1. BiDil
 Ethical Issues Raised by BiDil

BiDil is a combination of 2 drugs that

have been available in genetic form for
decades: hydralazine and isosorbide
(nitroglycerin).

It was postulated that this combination of

drugs would benefit individuals with end-
stage cardiovascular disease.
In 1997, the FDA rejected the drug after
a trial in a mixed race group, although a
subgroup of African American subjects
appeared to show benefit.

Medco then sold its rights to BiDil to

Nitromed, Inc.
African Americans are more likely than
White Americans to have decreased
levels of nitric oxide, and BiDil is a nitric
oxide enhancer.

This was the biological hypothesis for an

improved outcome in this subpopulation.
Nitromed joined with the Association of
Black Cardiologists to sponsor the
African American Heart Failure Trial,
which involved 1,000 patients at 170
sites.

On July 19, 2004, the trial was halted

because of the significant success of
patients enrolled in the treatment arm of
the trial.
Results:
43% improvement in survival
and
33% reduction in first hospitalization.

A patent was issued for BiDil on August

31, 2004.
On December 23, 2004, a new drug
application was submitted to the FDA in
which approval was sought only for
African American patients.

Approval was granted on June 23, 2005

only for self-identified African
Americans.
Why has BiDil been a commercial failure?

• Substitution by physicians?
• Rejection by patients?
2. The importance of public
education and public trust
E. Personalized Medicine and Privacy

1. Generating genetic information

2. Commercial personal health records

(PHRs)

• Not covered by HIPAA

• Bankruptcy Issues