[Paleopsych] SW: On Race-Based Therapeutics
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Public Health: On Race-Based Therapeutics
http://scienceweek.com/2004/sc041210-5.htm
The following points are made by M. Gregg Bloche (New Engl. J. Med.
2004 351:2035):
1) Are we moving into a new era of race-based therapeutics? The recent
publication of the African-American Heart Failure Trial (A-HeFT), a
clinical trial of a medication intended for a single racial group,
poses this awkward question. The study's most striking finding -- that
the addition of isosorbide dinitrate and hydralazine to conventional
therapy for heart failure reduced relative one-year mortality by 43
percent among blacks -- has provoked wide discussion. The trial's
sponsor, NitroMed, which holds a patent on the fixed-dose combination
of isosorbide dinitrate and hydralazine that was used, posits that
heart failure has a different pathophysiology in blacks than in
whites, necessitating different treatment strategies.(1)
2) The reported 43 percent relative decrease in the rate of death due
to heart failure among blacks is cause for celebration. There is wide
agreement that blacks die from heart failure at rates disproportionate
to those among whites. But to assess A-HeFT's larger implications for
the role of race in therapeutic design, it is important to be clear
about what the study has not shown.
3) First, A-HeFT has not established that adding isosorbide dinitrate
and hydralazine to conventional therapy for heart failure yields
greater benefits for blacks than for other racial or ethnic groups.
The study, which enrolled only self-identified blacks, did not test
this hypothesis. The clinical and economic logic behind A-HeFT's
design has its roots in previous, multiracial studies that compared
isosorbide dinitrate and hydralazine with other investigational drugs,
administered in combination with different conventional therapies.
These therapies were standard in their day but are inferior to the
conventional therapy used today, which typically includes an
angiotensin-converting-enzyme (ACE) inhibitor. Indeed, one of these
previous studies helped to establish ACE inhibitors as standard
treatment. This trial compared isosorbide dinitrate and hydralazine
with the ACE inhibitor enalapril and demonstrated that enalapril
resulted in a greater overall reduction in mortality.(2)
4) An ill-defined subgroup of patients, though, did well when treated
with isosorbide dinitrate and hydralazine and fared poorly with
enalapril. Seizing on this opportunity, a biotechnology firm obtained
intellectual-property rights to a fixed-dose combination of isosorbide
dinitrate and hydralazine and sought approval from the Food and Drug
Administration (FDA) in 1996 to market this formulation as a new drug.
The FDA declined, citing statistical uncertainties in the trial
data.(1) That is when race entered the picture. A group of
investigators (including the holder of the patent on the combination
treatment) reanalyzed the previous clinical-trial data according to
race and concluded in 1999 that the combination treatment did as well
as enalapril at prolonging the lives of black patients with heart
failure.(3) Other work suggested that ACE inhibitors were less
effective in blacks than in whites.
5) At this point, it might have made clinical and scientific sense to
add isosorbide dinitrate and hydralazine to conventional therapy
(which by now typically included an ACE inhibitor) and to compare this
combination to conventional therapy alone -- for all patients with
heart failure, regardless of race. Such a trial had not been
performed, since the standard therapies used in earlier trials did not
include ACE inhibitors. But race consciousness offered a faster way
through the FDA's regulatory maze. In 1999, NitroMed obtained
intellectual-property rights to fixed-dose isosorbide dinitrate and
hydralazine and said it would seek FDA approval to market the
formulation as a therapy for heart failure in blacks. Two years later,
the FDA indicated to NitroMed that successful completion of a clinical
trial in black patients with heart failure would probably result in
approval.(1) This commitment gave rise to A-HeFT, and the publication
of this trial's results virtually ensures FDA approval.
6) We need not shy away from the potential benefits of race-conscious
therapeutics, but we should manage its downside risks. Greater
awareness among physicians and the public that race is at best a
placeholder for other predispositions, and not a biologic verity,
would be a first step. Beyond such awareness, companies -- such as
NitroMed -- that stand to gain from taking account of race could
commit a substantial portion of their profits to research on genetic,
psychosocial, and other mechanisms that might underlie racial gaps in
clinical response.(3-5)
References (abridged):
1. 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
2. Cohn JN, Archibald DG, Ziesche S, et al. A comparison of enalapril
with hydralazine-isosorbide dinitrate in the treatment of chronic
congestive heart failure. N Engl J Med 1991;325:303-310
3. Carson P, Ziesche S, Johnson G, Cohn JN. Racial differences in
response to therapy for heart failure: analysis of the
vasodilator-heart failure trials. J Card Fail 1999;5:178-187
4. Lifton RJ. The Nazi doctors: medical killing and the psychology of
genocide. New York: Basic Books, 1986
5. Cacioppo JT, Hawkley LC. Social isolation and health, with an
emphasis on underlying mechanisms. Perspect Biol Med
2003;46:Suppl:S39-S52
New Engl. J. Med. http://www.nejm.org
--------------------------------
Related Material:
ANTHROPOLOGY: ON HUMANS AND RACE
The following points are made by D.A. Hughes et al (Current Biology
2004 14:R367):
1) Systematists have not defined a "type specimen" for humans, in
contrast to other species. Recent attempts to provide a definition for
our species, so-called "anatomically modern humans", have suffered
from the embarrassment that exceptions to such definitions inevitably
arise -- so are these exceptional people then not "human"? Anyway, in
comparison with our closest-living relatives, chimpanzees, and in
light of the fossil record, the following trends have been discerned
in the evolution of modern humans: increase in brain size; decrease in
skeletal robusticity; decrease in size of dentition; a shift to
bipedal locomotion; a longer period of childhood growth and
dependency; increase in lifespan; and increase in reliance on culture
and technology.
2) The traditional classification of humans as Homo sapiens, with our
very own separate family (Hominidae) goes back to Carolus Linnaeus
(1707-1778). Recently, the controversial suggestion has been made of
lumping humans and chimpanzees together into at least the same family,
if not the same genus, based on the fact that they are 98-99%
identical at the nucleotide sequence level. DNA sequence similarity is
not the only basis for classification, however: it has also been
proposed that, in a classification based on cognitive/mental
abilities, humans would merit their own separate kingdom, the
Psychozoa (which does have a nice ring to it).
3) As for sub-categories, or "races", of humans, in his Systema
Naturae of 1758 Linnaeus recognized four principal geographic
varieties or subspecies of humans: Americanus, Europaeus, Asiaticus,
and Afer (Africans). He defined two other categories: Monstrosus,
mostly hairy men with tails and other fanciful creatures, but also
including some existing groups such as Patagonians; and Ferus, or
"wild boys", thought to be raised by animals, but actually retarded or
mentally ill children that had been abandoned by their parents. In his
scheme of 1795, Johann Blumenbach (1752-1840) added a fifth category,
Malay, including Polynesians, Melanesians and Australians.
4) Blumenbach is also responsible for using the term "Caucasian" to
refer in general to Europeans, which he chose on the basis of physical
appearance. He thought Europeans had the greatest physical beauty of
all humans -- not surprising, as he was of course European himself --
and amongst Europeans he thought those from around Mount Caucasus the
most beautiful. Hence, he named the "most beautiful race" of people
after their supposedly most beautiful variety -- a good reason to
avoid using the term "Caucasian" to refer to people of generic
European origin (another is to avoid confusion with the specific
meaning of "Caucasian", namely people from the Caucasus).
5) The extent to which racial classifications of humans reflect any
underlying biological reality is highly controversial; proponents of
racial classification schemes have been unable to agree on the number
of races (proposals range from 3 to more than 100), let alone how
specific populations should be classified, which would seem to greatly
undermine the utility of any such racial classification. Moreover, the
apparent goal of investigating human biological diversity is to ask
how such diversity is patterned and how it came to be the way that it
is, rather than how to classify populations into discrete
"races".(1-4)
References:
1. Nature Encyclopedia of the Human Genome. (2003). Cooper, D. ed.
(Nature Publishing Group),
2. Fowler, C.W. and Hobbs, L. (2003). Is humanity sustainable?. Proc.
R. Soc. Lond. B. Biol. Sci. 270, 2579-2583
3. Encyclopedia of Human Evolution and Prehistory. (1988). Tattersall,
I., Delson, E., and Van Couvering, J. eds. (Garland Publishing)
4. World Health Organization Website http://www.who.int
Current Biology http://www.current-biology.com
--------------------------------
Related Material:
EFFECT OF RACE AND SEX OF PATIENTS ON TREATMENT FOR CHEST PAIN
Notes by ScienceWeek:
Epidemiological studies have identified differences according to race
and sex in the US in the treatment of patients with cardiovascular
disease. Some studies have found that blacks and women are less likely
than whites and men, respectively, to undergo *cardiac catheterization
or coronary artery bypass graft surgery when they are admitted to the
hospital for treatment of chest pain or *myocardial infarction. In
contrast, other studies were unable to confirm that invasive
procedures are underused in women. One question that has not been
addressed directly by previous studies is the extent to which
attitudes of physicians (in addition to any possible social and
economic factors) are responsible for the differences in treatment
recommendations with respect to race and sex.
The following points are made by K.A. Schulman et al (New England J.
Med. 1999 340:619):
1) The authors report the results of a study to assess, in a
controlled experiment, treatment recommendations by physicians for
patients presenting with various types of chest pain. The authors
report they developed a computerized survey instrument, with actors
portraying patients with particular characteristics in scripted
interviews about their symptoms. A total of 720 physicians at 2
national meetings of organizations of primary care physicians
participated in the survey. Each physician viewed a recorded interview
and was given other data about a hypothetical patient, and the
physician then made recommendations about the care of that patient.
2) The authors report that women and blacks were less likely to be
referred for cardiac catheterization than men and whites (*odds ratio
= 0.6), respectively, and that analysis of the race-sex interactions
indicated that black women were significantly less likely to be
referred for catheterization than white men (odds ratio = 0.4).
3) The authors suggest their finding indicate that the race and sex of
patients independently influence recommendations by physicians for the
management of chest pain, and that decision-making by physicians may
be an important factor in explaining differences in the US in the
treatment of cardiovascular disease with respect to race and sex.
New Engl. J. Med. http://www.nejm.org
--------------------------------
Notes by ScienceWeek:
cardiac catheterization: (intracardiac catheterization) This involves
the passage of a catheter (a small-diameter tubular instrument) into
the heart through a vein or artery, to withdraw samples of blood,
measure pressures within the chambers of the heart or the larger
vessels of the heart, or to inject contrast media for visualization
techniques. The cardiac catheterization technique is used primarily in
the diagnosis and evaluation of congenital, rheumatic, and coronary
artery lesions, and to evaluate various dynamic aspects of cardiac
function.
myocardial infarction: (myocardial infarct) In general, an "infarct"
is an area of necrosis caused by a sudden insufficiency of blood
supply, and a "myocardial infarction" (cardiac infarction) is such
damage of an area of heart muscle, usually as a result of occlusion of
a coronary artery.
odds ratio: In this context, the ratio of the probability of an event
in one group to the probability of the event in another group.
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