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PERSPECTIVEBeing Specific About Race-Specific Medicine
Gary Puckrein’s paper "BiDil: From Another Vantage Point" misrepresents rather than refutes our previously published analysis of BiDil. Puckrein claims that if our analysis were to prevail, patients would be denied life-saving therapy. Any reasonable reading of our paper suggests exactly the opposite. Indeed, based on the evidence, we urge doctors to prescribe the generics or BiDil itself as they see fit, but without regard to the race of their patient.
READERS CONCERNED ABOUT health disparities need to pay attention to the rhetoric of the BiDil story, not just its facts. Gary Puckrein’s paper "BiDil: From Another Vantage Point" does not rebut our previously published paper on the subject, nor does it present the story from another vantage point, assuming that the phrase in its title is meant to suggest a broad view.1 Rather, the paper misrepresents our analysis of BiDil by asserting that we dismiss the severity of health disparities and treat BiDil’s efficacy as a fabrication; in a classical use of innuendo, Puckrein’s paper hints that we object to the African-American Heart Failure Trial (A-HeFT), study design on racist rather than scientific and logical grounds. Puckrein claims that if our analysis were to prevail, patients would be denied life-saving therapy. Any reasonable reading of our paper suggests exactly the opposite. We note the following as among the more significant problems with Puckrein’s critique of our paper: (1) Puckrein’s assertion that our argument would lead to denying patients lifesaving therapy is an inaccurate inversion of our critique. One of our primary concerns is precisely that as approved by the Food and Drug Administration (FDA), BiDil will be inaccessible to many patients who could benefit from it. Given the apparent positive impact on heart failure of combined dosages of isosorbide dinitrate and hydralazine hydrochloride, we are interested in seeing more, not fewer, people get these drugs. The race-specific patent to BiDil will obstruct, not facilitate, access to the drugs. (2) As we pointed out in our original Health Affairs paper, nobody—certainly not the doctors who participated in the A-HeFT trial, and not even NitroMed (the company that manufactures BiDil)—claims that BiDil will work only in African Americans.2 But with its misleading race-specific indication, many doctors will not think to prescribe BiDil to non–African Americans. Any non–African Americans who seek to get prescribed BiDil "off-label" might not be able to afford it because insurance companies might be less likely to provide coverage for such off-label use. And BiDil is expensive. At up to $10.80 per day, its cost is about seven times that of the equivalent combined dosage of hydralazine and isosorbide dinitrate. (3) Puckrein notes that the FDA has not approved any equivalents and that an earlier FDA study from 1996 did not find the generics used in the Vasodilator–Heart Failure Trial (V-HeFT) studies to be bioequivalent to BiDil. This passage obfuscates the issue in a manner that serves only to strengthen the commercial value of BiDil. His reference to the fact that there is no FDA approval for the separate use of hydralazine and isosorbide dinitrate to treat heart failure is both disingenuous and dangerously misleading. First, the FDA does not recommend practice guidelines; it evaluates the safety and efficacy of drugs that are submitted to it for approval. No one has submitted the generics to the FDA for approval to treat heart failure because they are already out on the market, approved for other uses. It is organizations such as the American Heart Association (AHA) that promulgate practice guidelines; the most recent AHA guidelines for heart failure—issued after the FDA approval of BiDil—pointedly do not reference BiDil but, rather, the co-administration of the two generics, hydralazine and isosorbide dinitrate, as approved therapy for heart failure.3 Second, Puckrein might be well advised to consult with Jay Cohn, the lead investigator on the V-HeFT studies and the holder of both patents to BiDil. On the eve of BiDil’s approval, Cohn stated that he had been prescribing the generic drugs that make up BiDil for the 25 percent of his white patients who did not do well on other drugs.4 (4) Puckrein again gets things exactly backward when he criticizes us for objecting to the race-specific design of the A-HeFT trial but not to all of the drug trials that were conducted only or primarily in whites. Our objection was not simply to the race-specific design but to the subsequent interpretation of the data that asserted that race was a relevant biological variable in assessing the results. The A-HeFT results cannot tell us whether BiDIl works differently or better in African Americans than in anyone else because the study did not compare African Americans to anyone else. Indeed, Cohn has said that he believes that BiDil will probably work in people regardless of race and that "everybody should be using it."5 When the FDA approved the multitude of drugs based on studies conducted in white populations, it did not presume race to be a relevant biological variable. Rather, its approval was premised on the assumption that in drug studies, the category "white" was coextensive with the category "human being." The same assumption should apply to the category "African American." If you carried Puckrein’s argument to its logical conclusion, most of the drugs on the market today would be labeled for whites only—certainly not a desirable result. (5) Puckrein also spends considerable time taking issue with earlier articles by Kahn that criticize the misuse of statistics to frame heart failure as a distinctively "black disease." Specifically, Kahn’s work notes how NitroMed and others asserted that blacks die from heart failure at twice the rate of whites and goes on to show that in fact the ratio was about 1.08:1. Puckrein does not find any inaccuracies in this earlier work but tries to minimize its significance. He falls back, as NitroMed has, on more recent statistics showing that for people ages 45–64, African American men have a death rate that is 2.5 times higher than that of Caucasian men, and African American women have a death rate that is 2.7 times higher than that of Caucasian women. These statistics are accurate and significant. Early onset of heart failure is important, and its causes are worthy of attention. BiDil, however, was not approved to treat "early onset" heart failure but heart failure generally. Puckrein fails to mention that only about 6 percent of overall mortality from heart failure occurs in the 45–64 age range. About 93 percent of mortality occurs after age sixty-five, and in that group there is almost no difference in age-adjusted mortality rates between blacks and whites.6 (6) Finally, Puckrein raises the issues of a purported racial difference in response to angiotensin-converting enzyme (ACE) inhibitors. Instead of hashing over the technical debates in the literature, we simply note the following: The International Society on Hypertension in Blacks recommends the use of ACE inhibitors in black patients; and nearly 70 percent of the African American subjects in A-HeFT were on ACE inhibitors.7 In the end, as Cohn has said, he prescribes the generics and thinks that "everybody should be using" BiDil. We agree. So we urge doctors to just "be like Jay": prescribe the generics or BiDil itself as you see fit, without regard to the race of your patient.
Jonathan Kahn is an assistant professor at the Hamline University School of Law in St. Paul, Minnesota. Pamela Sankar (sankarp{at}mail.med.upenn.edu) is an associate professor in the Department of Medical Ethics, University of Pennsylvania, in Philadelphia. This work was supported by Public Health Service Grant no. R01 HG003191 to Pamela Sankar.
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