LEADING EDGE
Does Race Have a Place
In Biotechnological Research?
BY JACK MCCAIN
Senior Contributing Editor
O
n the basis of a clinical
trial in which the race
of heart failure patients
was self-reported (as
black), the U.S. Food and Drug Administration this year granted a
small Massachusetts biotech company, NitroMed, approval to market
the first race-based drug, BiDil.
Here’s what the label for BiDil, a
combination product of isosorbide
dinitrate and hydralazine, says:
BiDil is indicated for the treatment of
heart failure as an adjunct to standard therapy in self-identified black patients to improve survival, to prolong
time to hospitalization for heart failure, and to improve patient-reported
functional status (emphasis added).
If other pharmaceutical companies follow NitroMed’s lead, could
additional products be developed
with the supposedly special needs
of specific racial and ethnic groups
in mind? Is race a variable that deserves a place in biotechnological
research? Or should the idea be
tossed in the trash, fast? And does
the BiDil saga (see page 56) point to
a flaw in the drug approval process?
The FDA has adopted the same
race and ethnicity categories employed by the Office of Management and Budget. These categories
are used to collect census data or
monitor housing discrimination,
54 BIOTECHNOLOGY HEALTHCARE · DECEMBER 2005
PHOTOGRAPH BY STEVE WOIT
Now that we have the first race-based FDA indication, more may
follow. Is diversity necessarily a function of biology – and thus a
cause of health-outcomes disparities – or are we fixing molecules
at the expense of fixing society?
among myriad other purposes. The
FDA’s guidance for the pharmaceutical industry on the collection
of race and ethnicity data in clinical
trials, issued in September, notes
that these categories “were not anthropologic or scientifically based
designations.” On the other hand,
the guidance points to the clinical
relevance of various studies in
racially and ethnically distinct subgroups in which differences in response to medical products have
been observed, mentioning BiDil
specifically. In other words, it would
seem that the FDA endorses the use
of nonscientific categories in the
service of a science-based drugdevelopment process.
Eventually, routine genetic tests
may indicate whether a patient is a
good candidate for a given drug.
Genotyping tests already can identify patients whose genotype for
various cytochrome P450 enzymes
makes it likely that they are ultrarapid metabolizers of a drug (and
therefore unlikely to achieve a
therapeutic level at a normal dose)
Poverty, not race, is the critical
factor in disparities in health
outcomes between blacks and
whites, says Jonathan Kahn, JD,
PhD, of Hamline University
School of Law. Kahn told an FDA
committee considering approval
of BiDil for black patients that a
race-specific label would imply
that its use is inappropriate in
nonblacks.
or poor metabolizers (and therefore more likely to experience adverse effects). But, for the moment,
there’s no inexpensive way to tell in
advance whether or how a patient
will respond to a drug, and the costeffectiveness of the available tests
has yet to be ascertained.
From the perspective of an individual physician confronting an individual patient, race might be one
of many factors taken into consideration. Peter Schulman, MD, a cardiologist at the University of Connecticut Health Center, says the
availability of BiDil doesn’t represent a new way of thinking about
matching drugs and patients, because physicians already take race
into consideration when contemplating therapies.
As examples of evidence that
might support race-based clinical
decisions, he cites the Beta-blocker
Evaluation of Survival Trial (BEST),
which raised questions about the
benefits of beta blockade, at least
with bucindolol, in black patients
with class III/IV heart failure, and a
study showing that, compared with
whites, some Asian subpopulations
retain higher blood levels of rosuvastatin (Crestor). In fact, its manufacturer, AstraZeneca, has launched
three phase 4 trials to determine the
statin’s efficacy and safety in populations designated by race or ethnicity: ARIES (African-American
Rosuvastatin Investigation of Efficacy and Safety), IRIS (Investigation
of Rosuvastatin In South Asian
Subjects), and STARSHIP (STudy
Assessing RosuvaStatin in the HIspanic Population).
“I have no problem with using
race to help tailor therapy for an individual patient,” says Schulman.
“You want to provide optimal therapy for all your patients,” he says. To
that end, Schulman says he would
consider using BiDil in a white patient if the circumstances warranted, though so far he has yet to
prescribe it for anyone.
IT’S ABOUT POVERTY
Jonathan Kahn, JD, PhD, a lawyer
from Hamline University School of
Law, in St. Paul, Minn., has a different perspective. Kahn, who has followed BiDil very closely (Kahn
2003, 2004), spoke before the FDA’s
cardiovascular advisory committee
in June when BiDil was being considered for approval. Kahn told the
committee there is a difference
between a physician’s use of probabilistic correlations with race or
ethnicity to guide dosage and administration (as Schulman does)
and the establishment of a racespecific label for a drug.
Kahn says that although physicians may have been trained to take
race into consideration and feel
comfortable using it to inform prescribing decisions, it would be more
helpful to ask about a patient’s ZIP
code or income, because that information is likely to be more useful
DECEMBER 2005 · BIOTECHNOLOGY HEALTHCARE 55
LEADING EDGE
Evolution of BiDiL, the first race-based drug
1980–1985 — Vasodilator Heart Failure Trial (V-HeFT I) finds that, in CHF patients receiving background
therapy of digoxin and a diuretic, the alpha-blocker prazosin is no better than placebo in
reducing mortality, whereas the combination of hydralazine and isosorbide dinitrate does
reduce mortality.
1986–1991 — V-HeFT II compares hydralazine/isosorbide dinitrate against the ACE inhibitor enalapril and
establishes ACE inhibitors as first-line treatment for heart failure; this combination is reserved for patients intolerant of ACE inhibitors.
1987
— Jay Cohn, a principal investigator in the V-HeFT trials, applies for a patent for the use of
hydralazine/isosorbide dinitrate to reduce mortality associated with congestive heart failure.
1989
— Cohn is awarded a patent, which will expire in 2007.
1992
— Trademark application filed for a single pill combining hydralazine and isosorbide dinitrate, BiDil.
1995
— Trademark registered to Medco Research, which acquired intellectual property rights to
BiDil from Cohn.
1996
— BiDil new drug application submitted to FDA for approval.
1997
— FDA rejects BiDil application, on the grounds that a retrospective analysis of V-HeFT data
was inadequate statistically; Medco allows intellectual property rights to revert to Cohn.
1997
— FDA Modernization Act calls for the development of guidance on inclusion of women and
minorities in clinical trials.
1999
— Cohn and colleagues publish a retrospective analysis of V-HeFT data (Carson 1999).
1999
— NitroMed obtains intellectual property rights to the fixed-dose combination of isosorbide
dinitrate and hydralazine, then announces its intention to seek FDA approval to market
this combination as treatment for heart failure in blacks.
2000
— Cohn and Peter Carson file a patent application for the use of hydralazine/isosorbide to
treat heart failure in African-Americans.
2001
— FDA tells NitroMed that a successful trial of combination product in blacks with heart failure probably would lead to marketing approval; African-American Heart Failure Trial (AHeFT) begins enrolling patients to investigate hydralazine/isosorbide dinitrate as a treatment for heart failure in African-Americans.
2002
— U.S. patent number 6,465,463 awarded to NitroMed for using hydralazine/isosorbide to
treat heart failure in African-Americans, the first granted to an existing drug for a racespecific use. Patent expires 2020.
2004 (July) — A-HeFT is terminated prematurely after a 43 percent improvement survival was seen in
BiDil group relative to placebo group.
2004 (Nov.) — Results of A-HeFT published (Taylor 2004).
2005 (June)— FDA approves BiDil for the treatment of heart failure as an adjunct to standard therapy in
self-identified black patients.
SOURCE: KAHN 2004
than asking (or making assumptions) about the patient’s race. ZIP
codes and income levels provide
clues about affluence or, more importantly, the lack thereof. Poverty,
he says, not race, is the critical factor in disparities in, for example,
survival rates between black and
white cancer patients (Bach 2002).
Harold P. Freeman, MD, the director of the National Cancer Institute’s Center to Reduce Cancer
Health Disparities, points in his
writings to the convergence of
poverty and culture, not race itself,
as the explanation for excess mortality in certain groups. He points
out that health outcomes are simi-
56 BIOTECHNOLOGY HEALTHCARE · DECEMBER 2005
lar in predominantly black Harlem,
N.Y., and predominantly white Harlan, Ky. In both settings, Freeman
says, the combination of poverty
and culture are factors in overconsumption of fatty and salty
foods, alcohol, and tobacco. Race
need not be invoked.
But if poverty is associated with
LEADING EDGE
poor health, and if poverty is inequitably distributed among racial
and ethnic groups, then statistical
portraits of racial and ethnic groups
will capture the resulting differences
in disease prevalence and mortality.
Gregory Dorr, PhD, a historian with
an interest in the intersection of race
and medicine, notes that the median
wealth of blacks in the United States
is one tenth that of whites.
“Would anyone seriously suggest
that a genetic difference of 0.02 percent accounts for such a gross economic disparity?” asks Dorr, a postdoctoral associate at MIT’s Center
for the Study of Diversity in Science,
Technology, and Medicine. “No one
wants to hear this, because it
smacks of redistribution of wealth.
Our culture prefers to seek technological solutions for social problems, but that approach comes with
unintended consequences.”
Foremost among these, Dorr
fears, is that it bestows government
sanction on racial categories — giving implicit legitimacy to racial categories that have no genetic basis.
“The last time we labeled something for blacks only it was water
coolers and bus seats,” he says.
Although the genetic differences
between races are very small, the
social differences are immense,
Dorr maintains. Unfortunately,
there is a long, inglorious history in
the United States of ascribing differences in mortality rates between
whites and blacks to inherent biological differences, all the while invoking the name of science. The
seminal document was Race Traits
and Tendencies of the American Negro
(1896), by the highly influential statistician and actuary Frederick L.
Hoffman (1865–1946). After analyzing data from the 1890 census,
Disparities between blacks and whites in age-adjusted
death rates for heart disease, cancer, and diabetes
Annually, per 100,000 population
600
Heart disease
500
Black
White
400
300
Black
Cancer
200
White
100
Diabetes
0
Black
White
1950
1960
1970
1980
1990
2000
SOURCE: HEALTH, UNITED STATES, 2004 (TABLE 29), NATIONAL CENTER FOR HEALTH
STATISTICS
Hoffman claimed the statistics
demonstrated that blacks were
overly susceptible to illness, constitutionally unfit for survival — and
destined for extinction.
“From this perspective,” Dorr
says, “slavery was construed as salubrious, because it helped blacks
who could not survive as well on
their own. Absent slavery, Southerners justified segregation as necessary to prevent race war and black
extinction through disease.”
Why do humans attach such importance to race? Biologist Richard
Dawkins, author of The Selfish Gene
and other books, says our insistence
in assigning people to rigid racial
and ethnic categories is an exam-
ple of the “tyranny of the discontinuous mind” — a mind that is
uncomfortable when grappling
with continuous variables. Dawkins
speculates that because humans associated the external appearance of
their mates with appealing cultural
characteristics, sexual selection
gave rise to widely varying superficial features among various populations, much as dog breeders selected for appealing characteristics
of domesticated wolves that led,
rather rapidly, to the emergence of
breeds as visually distinct as Dachshunds and Great Danes. But under
the fur, a dog is a dog, biologically
speaking, and under the skin of
whatever hue, a person is a person.
DECEMBER 2005 · BIOTECHNOLOGY HEALTHCARE 57
LEADING EDGE
“Even though, if you take the totality of genes into account, we are
a very uniform species, we are astonishingly variable in superficial
features that are trivial but conspicuous,” Dawkins has written.
The very conspicuity of trivial
racial features has had nontrivial
biological consequences, however,
with respect to patterns of disease
prevalence and mortality, because
race often is the reason for socioeconomic inequities and patterns
of behavior that provide different
populations with varying levels of
access to health care. As the NCI’s
Freeman(2003) has written:
becomes invisible. So do lots of
black patients in the context of the
common knowledge that blacks
don’t respond well to ACE inhibitors. It may be true that, in general,
blacks don’t respond as well to beta
blockers and ACE inhibitors as do
whites, and blacks in general respond
better than whites to diuretics and
calcium channel blockers, as a
meta-analysis by Seghal (2004) has
shown. But the same meta-analysis
also shows that 80 to 90 percent of
blacks and whites respond similarly
to these agents. Seghal’s conclusion:
“Race has little value in predicting
antihypertensive drug response.”
At this time, it appears that the single most important, and perhaps
only valid, reason for continuing to
use racial classification is to measure
and monitor the effects of past and
present social injustice. If people are
grouped in a certain category and
treated differently, then being in the
category itself is the problem.
EVOLUTION OF BIDIL
BiDil combines fixed doses of
two older vasodilators, hydralazine
37.5 mg and isosorbide dinitrate 20
mg, both of which are available as
inexpensive generics and long used
to treat heart failure patients who
can’t tolerate ACE inhibitors. BiDil
started out following the conventional route to approval — generating data from the V-HeFT (Vasodilator Heart Failure Trial) studies in
the general population — but when
its initial NDA was rejected, the investigators revisited their data and
saw that the hydralazine/isosorbide
dinitrate combination seemed to be
more effective in a small subpopulation of black subjects.
In the meantime, there had been
calls for greater involvement of
women and minority groups in clinical trials, and the FDA gave the goahead for a trial of BiDil in a population of self-described black
patients with heart failure. About
60 percent of the patients were male,
with a mean age of 57; 95 percent
had New York Heart Association
class III heart failure, with a mean
Sickle cell disease is commonly
held up as an example of how race
is associated with certain diseases.
Everybody knows sickle cell disease
is a black disease, right? But in fact,
sickle cell disease isn’t a function of
having black African ancestors; it’s
a function of having ancestors from
regions where malaria was endemic. So although the sickle cell
gene is most commonly found in
people with sub-Saharan ancestry
(but not in blacks from southern
Africa), it’s also found in Mediterranean, Middle Eastern, and Indian
populations — anywhere malariainduced evolutionary pressures
have come into play.
The problem is that when everybody knows sickle cell disease is a
black disease, the nonblack patient
58 BIOTECHNOLOGY HEALTHCARE · DECEMBER 2005
ejection fraction of 24 percent. The
trial was stopped prematurely after
a 43 percent reduction in mortality
was observed among patients receiving BiDil in comparison with
those receiving placebo.
The approval of BiDil was heralded as a therapeutic advance for
black patients with heart failure, and
perhaps it is; few have suggested
otherwise. But soon after its approval, NitroMed was quick to suggest that BiDil was likely to be effective in other populations, too. Does
it really work better in blacks than in
whites? No one knows, because the
African-American Heart Failure
Trial (A-HeFT, a subsequent trial of
the product in blacks with heart failure) didn’t examine that question.
Treatment of heart failure has
changed substantially since the VHeFT trials were conducted in the
1980s, with ACE inhibitors and beta
blockers now being employed routinely in addition to diuretics and
digitalis. Something else that has
changed in recent years is that mortality rates for heart failure have declined in general, but most notably
among black men and women. U.S.
Centers for Disease Control and Prevention data show that between
1980 and 1995, total annual deaths
attributed to heart failure increased
from 27,415 to 46,484, with 94 percent of the 1995 deaths occurring in
patients who were 65 or older. (The
median age of A-HeFT subjects was
57, so even if the benefits of BiDil
extend beyond self-described
blacks, A-HeFT doesn’t speak to the
age at which the vast majority of
heart failure mortality occurs.)
In the 65-and-up age group, ageadjusted death rates increased between 1980 and 1988 but then
began falling, by annual rates of 3.0
LEADING EDGE
percent in black men, 2.2 percent
in black women, 1.7 percent in
white men, and 0.5 percent in white
women. As a result, the black:white
mortality ratio for men fell from
1.3:1 to 1.1:1 between 1980 and
1995; for women, from 1.4:1 to
1.1:1. The CDC speculates that improvements in detection and treatment of hypertension, myocardial
infarction, and heart failure are responsible for declining death rates
in black adults and white men, and
that the diminishing disparity in
the black-to-white mortality ratio
stems from improved control of
hypertension and access to medical
care among older blacks.
In his remarks to the FDA advisory committee, Kahn argued that
BiDil should be approved for use in
the general population without regard to race. “Most drugs on the market today were approved by the FDA
based on trials conducted almost exclusively in white patients,” he said,
“but those drugs are not designated
as white drugs, and rightly so....
When approving drugs tested in
white populations, the proper assumption of the FDA was that the
category white people did not differ in
any meaningful way from the category human being. The same assumption should apply to a drug tested in
an African-American population.”
Kahn pointed out that A-HeFT
enrolled only self-identified blacks,
so there is no scientific basis to
claim that BiDil works differently
in other racial or ethnic groups.
Rather than guide physicians in the
selection of drugs, he argued, a racespecific label for BiDil would direct
them to use it only in blacks and
would imply that its use is inappropriate in nonblacks.
Charles L. Curry, MD, chief of the
Notable notions
“While attempting to provide medical benefit, or market products, scientists and the pharmaceutical industry may reinvigorate the very notions of biological difference that may have
resulted in racially disparate treatment and racially disparate
health” (Ossorio and Duster 2005).
“The continued use of ‘race’ in biomedical research is contrary
to the goals of personalized medicine” (Shields 2005).
“Every human being is genetically unique and so must be
treated as an individual, not an example of a group defined by
geography or race” (Bamshad 2005).
“Geographic origin, patterns of intermating, and migration are
strong determinants of population characteristics; these populations are not equivalent to race” (Freeman 2003).
“The frequency of variant alleles and their encoded proteins
varies among populations according to race and ethnic background. However, for a patient, the critical determinant is the
genotype of the particular enzyme and not race or ethnic
group, which is assigned by subjective criteria” (Wilkinson
2005).
“The publication of the first draft of the sequence of the
human genome should force an end to medical research that is
arbitrarily based on race. The Human Genome Project now
gives us the power to uncover the true origins of genetic variations; linking them to race has become passé” (Schwartz 2001).
“[Race-based] research mistakenly assumes an inherent biologic
difference between black-skinned and white-skinned people. It
falls into error by attributing a complex physiological or clinical
phenomenon to arbitrary aspects of external appearance”
(Schwartz 2001).
Division of Cardiovascular Diseases
at Howard University College of
Medicine and president of the board
of trustees of the International Society of Hypertension in Blacks,
spoke immediately after Kahn. “I
could almost say ‘Amen’ to what Dr.
Kahn just said and sit right down,”
Curry told the panel. Endorsing the
approval of BiDil for any patient
without respect to race, he noted
that American cardiologists readily applied the results of the Scandinavian Simvastatin Survival
Study broadly, instead of restricting statin therapy to Scandinavians.
Three experts from the National
Human Genome Center (NHGC) at
Howard University also spoke, including Charles Rotimi, PhD. In
2003, NHGC hosted a workshop,
“Human Genome Variation and
‘Race,’” that was the basis for a supplement to Nature Genetics last year.
The workshop and supplement
were sponsored by the U.S. Department of Energy’s Office of Science,
whose director wrote in the intro-
DECEMBER 2005 · BIOTECHNOLOGY HEALTHCARE 59
LEADING EDGE
duction to the supplement: “The
solid science presented in this issue
… is providing proof that oversimplified concepts of race simply don’t
work in any objective realm. It’s bad
medicine, and it’s bad science.”
During the FDA meeting, Rotimi
said, “It would be tragic not to approve [BiDil] and it would be even
more tragic just to approve it for
African-Americans.” Rotimi, an epidemiologist who came to the United
States from Nigeria in 1981, asked
why blacks are at elevated risk for
numerous conditions. He said, “Are
they just selectively acquiring bad
genes? I don’t think so. There must
be something in our social environment that drives people toward poor
health, and only by addressing that
can we reduce health disparity.”
He showed them data from his
own research depicting how environment, not race, is the driving
force behind hypertension in
blacks.1 He also showed them data
from Seghal’s aforementioned metaanalysis (2004) indicating that the
majority of whites and blacks respond similarly to commonly used
antihypertensive agents. He closed
his remarks by asking what good is
a drug that reduces heart failure
mortality if it leads biomedical research down the wrong path by suggesting, without proper scientific
justification, that the so-called racial
categories are biological?
Two of Rotimi’s colleagues at
NHGC, Charmaine Royal, PhD, and
Vera Ota Wang, PhD, a voting
1 In rural Nigeria, the frequency of a genetic
variation associated with hypertension is
around 90 percent, and it is nearly that high
among urban African-Americans. However,
whereas the rate of hypertension is about 34
percent among the urban African-Americans, in Nigeria the rate of hypertension is
only 7 percent.
member of the FDA advisory committee, also spoke. Royal asked how
blacks would be identified in the
clinical setting. Would there be standardized national criteria to determine who is eligible for BiDil?
Would patients be allowed to selfidentify (as was done in A-HeFT), or
would the physician decide who is
or is not black?
Ota Wang questioned the rationale of the A-HeFT researchers for
using a self-reported racial category
as an inclusion criterion instead of
a more direct, quantitative biological trait. “There is a presumption here that, somehow, this selfidentified social identifier is
somewhat equivalent or representative of a biological process, and I
am not sure it really is.... We need to
look carefully at the issue of selfidentified racial categories, because
if the assumption is that these population differences are biological,
the self-identified population is a
social and political construct.”
But if comments like these
elicited a response at all, it was to
dismiss them. Said the advisory
committee’s chairman, Steven Nissen, MD, the oft-quoted Cleveland
Clinic cardiologist:
Drugs aren’t racist; people are....
[In this committee] we try to identify
whether a drug has efficacy and the
population that the drug will benefit. When the overwhelming evidence that leads me to believe that
this drug is effective comes from a
population we can define by some
characteristic — self-identified race, in
this case — that is very unusual. It is
precedent-setting....
We are moving toward the era of
genomic-based medicine, [where]
we are going to have the ability to
look for an SNP [single nucleotide
polymorphism] that tells us that this
group of people will benefit from x
60 BIOTECHNOLOGY HEALTHCARE · DECEMBER 2005
drug or will be harmed by y drug....
We already know that there are differences [in people of African origin]. We know, for example that ACE
inhibitors don’t seem to work as well
in African-Americans. We know that
certain diseases are more or less prevalent.... We are using self-identified race
as a surrogate for genomic-based medicine and I don’t think that is unreasonable....
I wish we had the genetic markers
... to decide who is going to respond
to what drug. But in the absence of
that, we have to use the best available
evidence, and that evidence was used
in this trial and it worked.
Said an FDA representative,
“What are the choices one has? This
is sort of what you work with because it is the best you have and
everyone agrees it is inadequate.”
In other words, pragmatism
trumps science.
CONNECTING RACE, HEALTH
As President Bush spent part of
2005 attempting to build support
for his idea to let workers invest
some of their Social Security withholdings in private accounts, he advanced an interesting argument:
“African-American males die
sooner than other males do, which
means the system is inherently unfair to a certain group of people.”
Bush suggested that because the
average age of death for an AfricanAmerican man is 69, versus 75 for a
white man, black men have fewer
years to enjoy Social Security benefits after they retire.
What about being AfricanAmerican leads to death at an earlier age? Was Bush perhaps referring to certain inherent biological
differences between black and
white men that naturally result in
shorter life expectancies for blacks?
LEADING EDGE
The statistics Bush cited were life
expectancies at birth for males born
in 2001. For the purpose of the Social Security debate, it might be
more useful to look at life expectancies for males approaching retirement age. According to the
CDC, black and white males born in
1950 could expect to live an average
of 59 and 66 years, respectively.
With respect to Social Security
retirement benefits, however, an
even more pertinent statistic would
be years of life remaining for males
who are 65 years old. As of 2002,
black males at age 65 had 14.6 years
of life remaining, not much fewer
than the 16.6 years remaining for
white males. (In 1950, years of life
remaining for 65-year-old black and
white males averaged 12.9 and 12.8
years, respectively.) That is, once
most men make it to 65, they’re
still looking forward to about 15
more years of life, on average.2
Close inspection of the table
above shows that blacks generally
have higher death rates for nearly all
the causes listed — cancer, cardiovascular disease, diabetes. Could it
be that blacks have certain biological
characteristics that make them more
susceptible than members of other
racial groups to the major killers? If
so, should research be aimed at developing drugs that specifically target these biological differences?
A longitudinal view shows a different picture. The age-adjusted
mortality rates for heart disease,
cancer, and diabetes in 1950 and
1960 suggest that at that time blacks
were just as healthy (or not) as
whites (see chart on page 57). But
2
Higher rates of infant mortality, HIV infection, and homicide among black males
account largely for the difference between
blacks and whites in total life expectancy.
Age-adjusted death rates for selected conditions
United States, 2002, per 100,000 population
All causes
Diseases of heart
Ischemic heart disease
Cerebrovascular diseases
Malignant neoplasms
Trachea, bronchus, and lung
Colon, rectum, and anus
Prostate
Breast
Chronic lower respiratory diseases
Influenza and pneumonia
Chronic liver disease and cirrhosis
Diabetes mellitus
Black or
African-American
White
1,083.3
308.4
203.0
76.3
238.8
61.9
26.8
62.0
34.0
31.2
24.0
8.5
49.5
837.5
239.2
171.0
54.6
195.6
57.5
19.5
25.8
25.6
46.9
22.6
9.0
22.2
SOURCE: HEALTH, UNITED STATES, 2004 (TABLE 29), NATIONAL CENTER FOR HEALTH
STATISTICS
since then, mortality rates for blacks
and white have diverged. Whereas
in 1950, the diabetes death rate was
essentially the same for blacks and
whites, by 2000 it was more than
twice as high among blacks. Even
though rates of death from heart
disease have declined in both
groups, by 2000 the mortality rate
among blacks was 30 percent
greater than that among whites. So
was the mortality rate from cancer.
What happened over the course
of 50 years? A lot of new drugs were
developed during that interval, so
do blacks just happen to respond
more poorly to all or most of them,
owing to genetic differences in drug
metabolism? Are blacks more susceptible genetically to a host of environmental risk factors for these
diseases that have emerged just during the last half century? Perhaps
there’s just something about the biology of self-described African-
Americans that is different. As the
chairman of the FDA advisory committee contemplating BiDil said in
June, “The road to hell is paved with
biological plausibility but there is a
biologically plausible explanation.”
Once you start considering races
to be sufficiently distinctive genetically to explain health disparities
between them, there’s no telling
where it will lead you. This slippery
slope worries sociologist Troy
Duster, PhD, immediate past president of the American Sociological
Society. In recent publications
(Duster 2005, Ossorio 2005), Duster
has noted that in 1950, the incarcerated percentages of the black and
white populations were 0.38 and
0.09 percent, respectively, a 4:1
ratio; by 1995, the shares respectively were 1.65 and 0.21, or 8:1.
To apply the logic that “genetic
differences between whites and
blacks explains widening variances
DECEMBER 2005 · BIOTECHNOLOGY HEALTHCARE 61
LEADING EDGE
in health outcomes” to Duster’s
point about incarceration, perhaps
you would have to advance an argument that some genetically based
propensity for criminal behavior
also was emerging amidst American blacks, too. Of course, over an
interval as short as 50 or 60 years,
the emergence of any evolutionary
changes in black and white biology
that might account for disparities
in health outcomes or incarceration
rates is highly implausible. At the
same time, it is likely that DNA data
compiled from people who have
been incarcerated would identify
certain SNP profiles that are found
at statistically significant higher
rates in blacks — simply because
black inmates outnumber white inmates. Duster warns that if race is
used as the phenotype to distinguish populations subjected to SNP
profiling, then once it becomes
widely available, “the likelihood of
committing the fallacy of misplaced
concreteness, in science, is nearly
overwhelming” (Duster 2005).
In the wake of the approval of
BiDil, it’s likely that drug companies far and wide are scurrying to reanalyze data from past studies that
might support a race-based indication that would extend the patentprotected life of a product.
What if, for example, Merck decided to pursue a race-based indication for losartan (Cozaar), which
was mentioned during the FDA advisory board meeting on BiDil as
an example of a drug presenting a
“huge hazard” in the black population but not in the white population? If NitroMed could do a retrospective analysis of BiDil data
among black patients, gain a racebased patent from the U.S. Patent
Office, and get FDA approval to run
a new clinical trial of BiDil in selfdescribed blacks, who could fault
Merck for doing a retrospective
analysis of its losartan data, getting
a new race-based patent, and conducting a trial that would lead to a
new race-based indication for losartan in patients with left ventricular
hypertrophy — but just for selfdescribed whites?
In fact, lots of people would fault
Merck, says Dorr, at MIT, because
whites with left ventricular hypertrophy aren’t regarded as a particularly disadvantaged group — and
because efforts to develop a whitesonly drug would suggest racism.
Then why could BiDil succeed
with a blacks-only approach? Dorr
says it’s because BiDil is viewed as
benign — a tool for narrowing disparities in health outcomes between blacks and whites.
“BiDil redirects peoples’ attention from knotty social problems
to slick — but flawed — technological fixes,” Dorr says.
Kahn holds a similar view. “I’m all
in favor of using race to track disparities in health care,” he says, “but
the approval of BiDil sends the message that, to the extent that there
are disparities, the solution is to fix
the molecules, not the underlying
problems.”
Stepping aside from the pragmatism that drives much of clinical
practice, it would appear that racebased medicines offer a quick fix —
and a profit for manufacturers willing to take advantage of the current
regulatory mindset — for problems
that are more than skin deep. BH
Based in Durham, Conn., Jack McCain is
a freelance medical writer and editor. He
holds degrees from Allegheny College and
Wesleyan University.
62 BIOTECHNOLOGY HEALTHCARE · DECEMBER 2005
FURTHER READING
Bach PB, Schrag D, Brawley OW, et al. Survival of
blacks and whites after a cancer diagnosis.
JAMA. 2002;287:2106–2113.
Bamshad M. Genetic influences on health. Does
race matter? JAMA. 2005;294:937–946.
Carson P, Ziesche S, Johnson G, Cohn JN. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure
trials. Vasodilator-Heart Failure Trial Study
Group. J Card Fail. 1999;5:178–187.
Cooper RS, Rotimi CN, Ward R. The puzzle of hypertension in African-Americans. Sci Am.
1999;280:56–63.
Dawkins R. The Ancestor’s Tale. 2004.
Duster T. Race and reification in science. Science.
2005;307:1050–1051.
FDA (U.S. Food and Drug Administration). Collection of Race and Ethnicity Data in Clinical Trials.
Rockville, Md.: FDA. September 2005. Available at: «http://www.fda.gov/cder/guidance/
5656fnl.pdf.» Accessed Sept. 30,. 2005.
FDA. Cardiovascular and Renal Drugs Advisory
Committee [transcript of meeting testimony].
Available at: «http://www.fda.gov/ohrms/
dockets/ac/05/transcripts/2005-4145T2.pdf».
Accessed Nov. 9, 2005.
Freeman HP. Commentary on the meaning of race
in science and society. Cancer Epidemiol Biomarkers Prev. 2003;12:232s–236s.
Jorde LB. Genetic variation and cardiovascular care.
Manag Care. 2004;13(10 suppl):9–13.
Kahn J. Getting the numbers right: statistical mischief and racial profiling in heart failure research. Perspect Biol Med. 2003;46:473–483.
Kahn J. How a drug becomes “ethnic”: law, commerce, and the production of racial categories in medicine. Yale J Health Policy Law
Ethics. 2004;4:1–46.
Kahn J. Misreading race and genomics after BiDil.
Nat Genet. 2005;37:655–656.
Nerenz D. Health care organizations’ use of
race/ethnicity data to address quality disparities. Health Aff (Millwood). 2005;24:409–416.
Ossorio P, Duster T. Race and genetics. Controversies in biomedical, behavioral, and forensic
sciences. Am Psychol. 2005;60:115–128.
Rotimi CN. Are medical and nonmedical uses of largescale genomic markers conflating genetics and
‘race’? Nat Genet. 2004;36(11 suppl):S43–S47.
Sankar P, Cho MK, Condit CM, et al. Genetic research and health disparities. JAMA. 2004;
291:2985–2989.
Seghal AR. Overlap between whites and blacks in
response to antihypertensive drugs. Hypertension. 2004;43:566–572.
Shields AE, Fortun M, Hammonds EM, et al. The
use of race variables in genetic studies of
complex traits and the goal of reducing
health disparities: a transdisciplinary perspective. Am Psychol. 2005;60:77–103.
Schwartz RS. Racial profiling in medical research
[editorial]. N Engl J Med. 2001;344:1393–1394.
Taylor AL, Ziesche S, Yancy C, Carson P, et al.;
African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate
and hydralazine in blacks with heart failure.
N Engl J Med. 2004;351:2049–2057. Erratum
in: N Engl J Med. 2005;352:1276.
Wang VO, Sue S. In the eye of the storm: race and
genomics in research and practice. Am
Psychol. 2005;60:37–45.
Wilkinson GR. Drug metabolism and variability
among patients in drug response. N Engl J
Med. 2005;352:2211–2221.
Williams DR, Jackson PB. Social sources of racial
disparities in health. Health Aff (Millwood).
2005;24:325–334.