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.

Gender representation in trials.

The perception is that women have been understudied relative to men. It has been sufficient to cause Congress to enact legislation to require that a clinical trial must be "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 ellipsis differently than other subjects in the trial." We looked for evidence as to whether the perception has a basis in fact by looking at measures of gender-based research effort. Clinical trials, published between 1966 and 1998 in U.S. journals and indexed in MEDLINE, were classified by gender. Reports of trials appearing in five widely circulated medical journals (Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine) in 1985, 1990, and 1995 were retrieved and read to obtain counts of the numbers of males and females represented in trials published in those journals. For reports of trials published in U.S. journals, the percent involving males and females, males only, females only, and those where gender was not specified were 55.2%, 12.2%, 11.2%, and 21.4%, respectively. Counts of males and females represented in the reports of trials appearing in the five aforementioned journals were 355,624 and 550,743, respectively. We did not find evidence of systematic effort bias against females.

Risk factors for advancement of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Studies of Ocular Complications of AIDS Research Group.

OBJECTIVE: To identify ocular and systemic factors that predict advancement of cytomegalovirus (CMV) retinitis during treatment. METHODS: Patients with acquired immunodeficiency syndrome were enrolled in a multicenter clinical trial designed to evaluate foscarnet sodium and ganciclovir sodium as therapy for newly diagnosed CMV retinitis. Ocular characteristics at baseline and measurements of retinitis were assessed from fundus photographs by graders at a fundus photograph reading center. The following measures of advancement were assessed: (1) lesion border movement of at least 750 microm or development of a new lesion in involved eyes; (2) rate of increase in retinal area with CMV in involved eyes; and (3) development of retinitis in uninvolved eyes of patients with unilateral disease at baseline. RESULTS: In eyes with retinitis, risk factors at baseline for advancement while receiving treatment included smaller area involved, active margins of retinitis, and posterior location. Risk factors for development of retinitis in uninvolved fellow eyes included blood and urine cultures positive for CMV and lower CD8(+) T-lymphocyte count. CONCLUSIONS: Lesion characteristics can be used to predict advancement of preexisting disease, whereas only systemic factors are associated with development of bilateral disease. These analyses describe retinitis activity before the introduction of potent antiretroviral therapies but provide an important reference point for patients in whom CMV retinitis develops after failure or intolerance of antiretroviral agents. Arch Ophthalmol. 2000;118:1196-1204