Do women react differently to drugs than men do? That remains a controversial issue 15 years after the National Institutes of Health opened a department dedicated to such research. "We worked hard with Congress to create that office," said Phyllis Greenberger, CEO of the Society for Women's Health Research in Washington, D.C. "And there's been considerable progress, but problems remain, especially in phase I and phase II trials."
Until the mid-1990s, women were included in the testing of new drugs at a much lower rate than men, except for gender-specific studies such as those conducted for contraceptives. Women of childbearing age were excluded from virtually all non-gender-specific trials. But since 1995, federal law has required that women of all ages be included in any new clinical trials. According to the NIH Office of Research on Women's Health (ORWH), women now comprise 50.2% of test subjects in non-gender-specific clinical trials.
But the data gathered and disseminated often fail to address whether the women in a study react in a different way to drugs than do the men, said Greenberger. "Inclusion of women in studies was taken to be the answer to the problem of lack of adequate data, but the question that needs to be asked the most still isn't being answered," she noted. "That is: Does a drug work as well as or differently on women than it does on men?
Greenberger said this is a continuing problem and pointed to a recently publicized study of the anticlotting drug Plavix (clopidogrel), manufactured by Sanofi-Aventis and Bristol-Myers Squibb, as an example. The study demonstrated that the drug is effective in reducing second heart attacks if taken with aspirin. Phase III of the study included 3,491 men and women (80.3% men), but nowhere in the results do researchers describe whether the drug affects men and women differently. "It simply never addresses that," she said. "That's an all-too-common flaw." (The results of the clinical tests were published in the March 24 edition of the New England Journal of Medicine in an article titled "Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation.")
In September 1990, bowing to pressure from Greenberger's organization and others, Congress created the ORWH within NIH to "strengthen and enhance research related to diseases, disorders, and conditions that affect women and ensure that research conducted and supported by NIH adequately addresses issues regarding women's health." In 1993, Congress passed the NIH Revitalization Act, which mandated that "women, minorities, and their subpopulations" be included in clinical trials.
In 2000, the Government Accountability Office, or GAO (then known as the General Accounting Office), reported that although NIH's efforts to include women in clinical trials were successful, phase III clinical trials were not being adequately designed and conducted to "allow for the valid analysis of differences between women and men." The GAO report added that drug companies were not being instructed to report those differences, if they exist.