Transcript Targeting Race Biomedical Interventions

Targeting Race
Biomedical Interventions
John R. Stone, MD,PhD
July 2005
Tuskegee University National Center for Bioethics in
Research and Health Care
[email protected]
Acknowledgements
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Harold Kincaid
Mona Fouad
Isaac Mwase
Ann Smith
June 2005
FDA approves Bidil
for treatment of
congestive heart
failure in
African Americans
FDA Approval of BiDil
•Much hype
•Good idea?
•Bad idea?
Ethical Issues/BiDil
Benefit Potential
Harm Potential
• Better CV health
for AA-perhaps
• Better health in
general for AA—
unknown
• Particularized care
• More efficiency
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Impersonal care
More stigma
More stereotypes
Reify race/biol
Reify race/genetics
Ignore social
Sustain, increase
injustices
Talking about race
• Uncommon in racially mixed
groups
• Uncommon in public
• Loaded
• Scary territory
• Opportunity for constructive
dialogue
• “The major task for Americans is to
analyze how and under what
circumstances we use the concept
of race.”
• “It is a mistake to discard race just
because racial categories do not
map exactly onto biological
processes. But it is also a mistake to
uncritically accept old racial
classifications when we study
medical treatments.”
Troy Duster, Buried alive: the concept of race in
science. The Chronicle Of Higher Education.
2001;48(3):B11 (emphasis added)
• “The task is to determine how
the social meaning of race can
affect biological outcomes like
varying rates of cancer and
heart failure. Burying the
concept of race can seem very
appealing in the short term. But
in practical applications, race
remains very much alive.”
Troy Duster, Buried alive: the concept of race in
science. The Chronicle Of Higher Education.
2001;48(3):B11 (emphasis added)
• “At the most basic level, it turns
out that BiDil became an ethnic
drug through the interventions
of law and commerce as much
as through medical
understanding of biological
differences that correlate with
racial groups.” (p. 3)
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law,
Commerce, and the Production of Racial Categories in
Medicine. Yale Journal Of Health Policy, Law, And Ethics
IV:1 (2004), p. 3 (emphasis added)
• “Race is at best a placeholder
for other predispositions, and
not a biologic verity.”
MG Bloche. Race-Based Therapeutics. NEJM
2004;351:2035-2037 (p. 2037) (emphasis added)
Possible legitimate
reasons to target groups in
medical care
• Enhance benefit (life, quality)
• “Particularize” or “personalize”
care (groups ≠ individuals)
• Reduce harms (death, suffering)
• Enhance efficiency
• Facilitate identification of
important factors (motive for
pharmacogenetics)
Questions
• Do investigator economic
interests matter in the BiDil
case?
• Do their conflicts of interest
undermine scientific validity?
Questions
• Should the FDA approve racetargeted biomedical interventions?
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• Never/always/sometimes
• What guidelines?
• What processes?
Safeguards?
Harms?
Benefits?
What after market monitoring and
safeguards?
Background
Congestive Heart Failure
(CHF)
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Early death
Sustained, progressive suffering
Huge problem
Causes (Europe/North America)
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Hypertension
Coronary artery disease
Valvular heart disease
Cardiomyopathies
Miscellaneous diseases
Background:
Earlier CHF Therapy
• Pathophysiology: peripheral vascular
constriction as CHF progresses
• Digoxin
• Diuretics
• Sodium restriction
• Blood pressure control
• Weight loss
• Cardiac surgery (mainly valvular)
CHF Outcomes
• Deaths AA/W reported >2:1
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law, Commerce, and the
Production of Racial Categories in Medicine. Yale Journal Of Health Policy,
Law, And Ethics IV:1 (2004);1-46.
CHF Clinical Trials
• Promote peripheral vasodilation
• Arterial
• Venous
• Hydralazine plus nitrates
• ACE Inhibitors
• ACE Receptor-blockers (much
later)
CHF Trials: Isosorbide
Dinitrate + Hydralazine
• Limited effectiveness of I + H
• ACE inhibitors
• More potent (better & longer lives)
• Less potent in AA-space for BiDil (Kahn)
• Better tolerated
• ACE inhibitors standard of care
• CHF
• Myocardial Infarction
• ACE receptor blockers as alternative
BiDil Story: CHF
• I/H: Isosorbide dinitrate + hydralazine
• 1980-1985: V-HeFT I, VA, , I/H
marginally > placebo, not Prazosin
(mortality)
• 1986-1991 V-HeFT II, ACE inhib > I/H,
ACE inhibfrontline, I/H backup if
intoler (mortality)
• 1987 Jay Cohn patent app I/H
combo, approv 1989, CHF (no race
mention)
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law, Commerce, and the
Production of Racial Categories in Medicine. Yale Journal Of Health Policy,
Law, And Ethics IV:1 (2004);1-46.
BiDil Story
• 1992 BiDil Trademark
• 1995 Medco intell prop rts f J Cohn
• 1996 Medco NDA-FDA-denied
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Cohn et al. arg f BiDil and Medco
Advisory committee votes against
Cohn+ arg f I/H’s efficacy (no race focus)
Biostatisticians, FDA Advis Com, argue
V-HeFT uncertainties about I/H efficacy
• MedCo returns intell prop rts to Cohn
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law, Commerce, and the
Production of Racial Categories in Medicine. Yale Journal Of Health Policy,
Law, And Ethics IV:1 (2004);1-46.
BiDil Story
• 1999: Peter Carson, Susan Zeische,
Gary Johnson, Jay Cohn.,
retrospective analysis (J Cardiac
Failure, v. 178):
• V-HeFT I: AA but not W ↓ mortality w/ I/H
(P = .04)
• V-HeFT I: Signif AA / W diffs, e.g. CHD
• V-HeFT II: only W ↓ mortality (P = .02),
• V-I: 180B/450W; V-II:215B/574W
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law, Commerce, and the
Production of Racial Categories in Medicine. Yale Journal Of Health Policy,
Law, And Ethics IV:1 (2004);1-46.
BiDil Story
• 1999: NitroMed intell prop rts f J Cohn
• 1999: J Cohn, P Carson app patent I/H f AA
w/ CHF, transfer rts to NitroMed
• 1999 P Carson, colleague publish review,
of LV dysf outcomes
• reconfirm 2:1 B/W mortality (older studies)
• assume underlying hypertension basically
biological because supposedly not based on
SES.
• CHF death rates 35-74, most W > age 74, B < 74
• most B CHF deaths < 74, so ignoring much data;
• unsophisticated SES analysis
• ignore recent stats sugg B/W mortal rates ~ 1.1:1
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law, Commerce, and the
Production of Racial Categories in Medicine. Yale Journal Of Health Policy,
Law, And Ethics IV:1 (2004);1-46.
BiDil Story
• 2001: Jay Cohn et al., NEJM, ACE
inhib less effective in blacks
(NitroMed’s V-HeFT underway)
• 2001 NitroMed gets support of ABC
(Assoc Black Cardiol) and
Congressional Black Caucus
• 2001 NitroMed raises $31 million
vent capital funds for A-HeFT
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law, Commerce, and the
Production of Racial Categories in Medicine. Yale Journal Of Health Policy,
Law, And Ethics IV:1 (2004);1-46.
BiDil Story
• 2004 (Nov) NEJM A-HeFT trial
• 1050 African Americans (selfidentified), randomized
• (I/H + best) or bestrandomized
• Early termination (deaths)
• 43% death reduct (10.2%6.2%)
Anne L. Taylor, et al. Combination of Isosorbide Dinitrate and Hydralazine in blacks
with heart failure NEJM 2004;351:2049-2057
June 2005
FDA approves Bidil
for treatment of
congestive heart
failure in
African Americans
Questions
• Do investigator economic
interests matter in the BiDil
case?
• Do their conflicts of interest
undermine scientific validity?
Questions
• Should the FDA approve racetargeted biomedical interventions?
•
•
•
•
• Never/always/sometimes
• What guidelines?
• What processes?
Safeguards?
Harms?
Benefits?
What after market monitoring and
safeguards?
Bidil & Race-targeting
Burdens/Harms?
• ▲ Injustices and Harms?
• ▲Stereotypes, bias, prejudice
• ▼Focus on health & healthcare ≠
• ▼Treatment for expensive minority
conditions?
• ▼ Genetics-based research?
• Race poor marker
• Group diff: only some genetic
Harms/BiDil Example
• Reinforces alleged connection
of race to biology & genetics,
• Pharmacogenetics focus diverts
attention from social factors in
health inequalities
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law, Commerce, and the
Production of Racial Categories in Medicine. Yale Journal Of Health Policy,
Law, And Ethics IV:1 (2004);1-46.
Bidil & Race-targeting
Benefits?
• ▲ Greater market motivation?
• ▲ Minority niche focus?
• ▲ Treatment for minority health
conditions?
• ▲ Opportunity for increased
minority input into treatment
development?
Race-targeting:
Checks & Balances
• Fair involvement of targeted populations in
FDA approval processes, including
enhanced representation on advisory
panels and approval boards.
• Fair selection of panel and board
members.
• Enhanced public input opportunities.
• Push after-market monitoring and national
registry
• Revise our health-care system and
relationships with industry (e.g., see
Marcia Angell-reference)
Ethical Issues/BiDil
Benefit Potential
Harm Potential
• Better CV health
for AA-perhaps
• Better health in
general for AA—
unknown
• Particularized care
• More efficiency
•
•
•
•
•
•
•
Impersonal care
More stigma
More stereotypes
Reify race/biol
Reify race/genetics
Ignore social
Sustain, increase
injustices
References
Marcia Angell, The Truth about the Drug Companies: How They
Deceive Us and What to Do About It. New York: Random House,
2004.
MG Bloche. Race-Based Therapeutics. NEJM 2004;351:2035-2037.
Troy Duster, Buried alive: the concept of race in science. The
Chronicle Of Higher Education. 2001;48(3):B11.
Jonathan Kahn. How a Drug Becomes “Ethnic”: Law, Commerce, and
the Production of Racial Categories in Medicine. Yale Journal Of
Health Policy, Law, And Ethics. 2004;IV:1:1-46