[Paleopsych] SW: On Race-Based Therapeutics

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Public Health: On Race-Based Therapeutics

    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
    New Engl. J. Med. http://www.nejm.org
    Related Material:
    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
    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:
    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
    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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