title: BiDil for heart failure in black patients: The U.S. Food and Drug Administration perspective.
abstract: Critics of the U.S. Food and Drug Administration (FDA) approval of the fixed combination of hydralazine hydrochloride, 37.5 mg, and isosorbide dinitrate, 20 mg, for treating heart failure in black patients have suggested that data were insufficient to distinguish treatment effects in black and white people; that distinctions based on race, rather than pathophysiology, were scientifically unreasonable; and that a "race-based" approval could be a commercial ploy to avoid a more expensive and prolonged full evaluation of a drug. The criticisms acknowledge that data supporting the approval came from a well-designed clinical trial in which self-identified black patients with heart failure who took hydralazine hydrochloride-isosorbide dinitrate with standard therapy experienced a statistically significant 43% (95% CI, 11% to 63%) reduction in mortality compared with those who took only the standard therapy. The criticisms do not always recognize that the decision to conduct the trial in only black patients reflected careful analyses of 2 previous trials in racially mixed patient populations that compared hydralazine hydrochloride-isosorbide dinitrate with placebo or with enalapril. Both trials showed little or no overall effect of hydralazine hydrochloride-isosorbide dinitrate in the mostly white patient population but hinted at a substantial effect in subsets of black patients. Perhaps most critically, the criticisms do not appreciate the urgency of strong scientific evidence of a substantial survival benefit in black patients. A serious attempt to avoid race-based approval by mandating study of a mixed population to identify a possible white patient-responder subset, particularly without a plausible hypothesis as to what that subset might be, would have required years of work, many thousands of patients, and wholly unreasonable delay in approval of a treatment whose effectiveness had been well-documented in the group for which it was intended.
authors.affiliation: U.S. Food and Drug Administration, Silver Spring, Maryland 20993-0002, USA. robert.temple@fda.hhs.gov
authors.forename: Robert
authors.initials: R
authors.lastname: Temple
authors.forename: Norman L
authors.initials: NL
authors.lastname: Stockbridge
mesh_terms: D044383:Black People; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D017277:Drug Approval; D004338:Drug Combinations; D006333:Heart Failure / Q000188:drug therapy* / Q000208:ethnology*; D006801:Humans; D006830:Hydralazine / Q000627:therapeutic use*; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D011640:Public Policy; D016032:Randomized Controlled Trials as Topic / Q000592:standards; D014481:United States; D014486:United States Food and Drug Administration; D001741:Black or African American
chemical_list: D002317:Cardiovascular Agents; D004338:Drug Combinations; C431665:isosorbide-hydralazine combination; D006830:Hydralazine; D007548:Isosorbide Dinitrate