For immediate release
Tuesday, Aug 15, 2006
12:01 a.m. EDT

 

Contact:
Christopher Fleming
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BiDil Is An Important Advance In The Fight Against Heart Failure’s Disproportionate Toll On The Black Community, Researcher Says

Puckrein Applauds FDA’s Race-Specific Approval Of BiDil;
Kahn And Sankar Say FDA’s Action Will Impede Access To Treatment

Bethesda, MD -- The Food and Drug Administration acted correctly when it approved BiDil to treat congestive heart failure in self-described African Americans, the first time the agency had ever approved any medication for a race-specific indication, Gary Puckrein writes in a Web-Exclusive article published today on the Health Affairs Web site.

“BiDil provides African Americans with an effective new weapon against heart failure,” said Puckrein, executive director of the National Minority Health Month Foundation. “Existing heart-failure medications don’t work as well for African Americans as they do for members of other racial and ethnic groups, and heart failure hits the African American community disproportionately hard.” Puckrein’s article responds to several arguments made by critics of the FDA’s race-specific approval of BiDil, including those voiced by Pamela Sankar and Jonathan Kahn in an 11 October 2005 Health Affairs Web Exclusive (see their original paper at http://content.healthaffairs.org/cgi/content/abstract/hlthaff.w5.455).

Manufactured by NitroMed, BiDil combines two generic compounds, hydralazine hydrochloride and isosorbide dinitrate. In a clinical trial known as the African-American Heart Failure Trial (A-HeFT), which involved just over 1,000 African American heart-failure patients, those receiving standard therapy plus BiDil saw a 43 percent improvement in survival, as compared with those taking the standard therapy plus a placebo.

Puckrein acknowledges that NitroMed overstated the case for BiDil by claiming repeatedly that “death rates from heart failure are more than twice as high in black patients than in white patients.” However, he stresses that there are marked racial disparities in heart-failure incidence and mortality among younger patients. In 2002, for instance, the ratio of black to white death rates from the disease was 1.71 to 1 for patients ages 35-74 and 2.54 to 1 for patients ages 35-64. Moreover, 17 percent of black heart-failure deaths occurred among patients ages 35-64, while only 5 percent of white heart-failure deaths were in this age cohort.

Puckrein: Racial Classifications In Medicine Are “Crude,”
But Needed Until Better Information Is Available

In any case, while “the unexplained and untreated disparity in premature death between African American and other heart-failure patients added urgency to the development of BiDil,” Puckrein writes, even “if there were no disparity in death rates, BiDil’s effectiveness would still justify its approval.” He acknowledges concerns regarding “the medical and scientific validity of the concept of race,” but he says that such concerns are, “under present circumstances, impractical.” In the long run, “the social concept of race will be superseded by more objective and precise criteria,” allowing specific African American and non-African American individuals who will benefit from BiDil to be identified. In the meantime, however, “current research and medical practices recognize racial and other crude distinctions, in the absence of more precise information, every day.”

Puckrein defends A-HeFT against charges that it should have included a non-African American control group by stating that A-HeFT’s designers had “extracted adequate evidence from [earlier multiracial studies] to justify narrowing the focus to the most promising group,” and that the black patients who received standard therapy and a placebo, instead of standard therapy and BiDil, functioned as a control group. “It could be argued that A-HeFT represents a rare instance of a trial that includes an adequate number of African American subjects,” Puckrein observes, and he adds of Sankar, Kahn, and other critics: “Oddly, they do not discount as unscientific clinical trials whose patient populations are all white or those in which minority populations are too small to represent meaningful samples.”

Finally, Puckrein rejects the argument that low-cost generics can be substituted for BiDil. “There is no FDA approval for the separate use of hydralazine and isosobide dinitrate for heart failure,” he points out. As for critics like Sankar and Kahn, who “find cause for skepticism in the commercial motivations of BilDil’s developers,” Puckrein suggests a wider focus: “Their quarrel here is with the system that drives the development of pharmaceuticals and other medical treatments in the United States and internationally.”

Kahn And Sankar: After FDA Action, Many Physicians
Might Not Think Of BiDil For Non-African Americans,
And Insurers Might Not Cover Such Off-Label Use

In a Perspective on Puckrein’s article, Kahn and Sankar label as “both disingenuous and dangerously misleading” Puckrein’s statement that the FDA has not approved the hydralazine and isosobide dinitrate (H/I) combination to treat heart failure. “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,” say Kahn, an assistant professor of law at Hamline Uninversity, and Sankar, an associate professor of medical ethics at the University of Pennsylvania. They point out that the American Heart Association’s most recent practice 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 . . . as approved therapy for heart failure.”

Kahn and Sankar also argue that “the race-specific patent to BiDil will obstruct, not facilitate, access to” the H/I combination. Many physicians “will not think to prescribe BiDil to non-African Americans,” and “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.” Kahn and Sankar additionally say that Puckrein’s statistics on racial disparities in heart failure among younger patients are “accurate and significant,” but they point out that BiDil “was not approved to treat ‘early onset’ heart failure but heart failure generally.”

Moreover, say Kahn and Sankar, Puckrein has it “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 [to A-HeFT] 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 Bi-Dil works differently or better in African Americans than in anyone else.

“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,” Kahn and Sankar add.

You can read the article by Puckrein at http://content.healthaffairs.org/cgi/content/abstract/hlthaff.25.w368

You can read the Perspective by Kahn and Sankar at http://content.healthaffairs.org/cgi/content/abstract/hlthaff.25.w375

ABOUT HEALTH AFFAIRS:

Health Affairs, published by Project HOPE, is the leading journal of health policy. The peer-reviewed journal appears bimonthly in print with additional online-only papers published weekly as Health Affairs Web Exclusives at www.healthaffairs.org.

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©2006 Project HOPE–The People-to-People Health Foundation, Inc.