Gender bias in clinical trials: do double standards still apply?

Differential enrollment into clinical trials by gender has been described previously. In 1993, the National Institutes of Health (NIH) Revitalization Act was enacted to promote the inclusion of women in clinical trials. The purpose of this study was to review patterns in clinical trial enrollment among studies published in a major medical journal to determine the effects of this policy. A systematic search was conducted of all articles published in the Original Articles section of The New England Journal of Medicine from 1994 to 1999. Two independent observers abstracted information from the randomized clinical trials using standardized forms. All randomized clinical trials in which the primary end point was total mortality or included mortality in a composite end point were considered for review. Trials were analyzed for enrollment of women with respect to disease state, funding source, site of trial performance, and use of gender-specific data analysis. From 1994 to 1999, 1322 original articles were published in The New England Journal of Medicine, including 442 randomized, controlled trials of which 120 met our inclusion criteria. On average, 24.6% women were enrolled. Gender-specific data analysis was performed in 14% of the trials. The NIH Revitalization Act does not appear to have improved gender-balanced enrollment or promoted the use of gender-specific analyses in clinical trials published in an influential medical journal. Overcoming this trend will require rigorous efforts on the part of funding entities, trial investigators, and journals disseminating study results.