Estimation of gender bias in clinical trials

The perception is that the clinical trials enterprise has been biased in favour of males by devoting a disproportionate effort to males and to the diseases and conditions afflicting them - a perception reinforced by a few high profile male-only heart trials undertaken in the 1970s and 1980s. The perception was sufficient to cause the U.S.A. Congress to enact legislation to require that a clinical trial 'is designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect women ...differently than other subjects in the trial'. Observed effort differentials are based on counts of single-gender trials indexed in MEDLINE and published in U.S. journals. Differentials are compared to those expected using male-female differentials in mortality and years of potential life loss due to mortality before age 65 to estimate effort bias. The ratios of female-only to male-only published trials were 0.53, 0.89 and 0.95 for the decades of 1966-1975, 1976-1985 and 1986-1995, respectively. The expected ratios, if single-gender trials were done in proportion to female-male mortality differentials, would be 0.57, 0.56 and 0.57, respectively. The differences in observed versus expected female to male ratios correspond to a slight excess of male-only trials in the decade of 1966-1975 and to sizeable excesses in female-only trials in the decades of 1976-1985 and 1986-1995. The results do not support the perception that women have been understudied relative to males in clinical trials. Most differentials favour females, whether based on mortality or years of potential life loss due to mortality before age 65 years.