Evaluation of ethnic minorities and gender effects in clinical trials: opportunities lost and rediscovered.

Recent recognition has been given to the notion of demonstrating a beneficial effect of randomly allocated interventions utilized in controlled clinical trials to women and ethnic minorities. However, despite National Institutes of Health (NIH) guidelines on the inclusion of ethnic minorities and women into these studies, clinical trial investigators continue to suffer from an inability to persuasively reach conclusions about the intervention effect in these subgroups. Although a major factor in this limitation has been the inability to recruit large numbers of these patients into controlled clinical trials, an additional dilemma has been the clinical trial community's well demonstrated inability to draw reliable conclusions from the relevant subgroup analyses. As currently designed in clinical trials, subgroup analyses with neither good prospective planning nor concern for the multiplicity of type I error that accompanies the testing of multiple hypotheses are appropriately relegated to exploratory analyses which merely raise questions, not answer them. This article demonstrates that taking advantage of: (a) prospective, subgroup specific endpoint selection; (b) prospective, subgroup specific endpoint event rates; (c) prospective, subgroup specific therapy efficacy, and (d) prospective, subgroup specific nonuniform type I error levels will fortify a subgroup analysis. Thus, the tools traditionally available to clinical trialists, when wielded with renewed vigor and innovation, in concert with energetic, focused recruitment efforts can lead to a confirmatory analysis with appropriate statistical rigor for the effect of the randomly allocated intervention in these important demographic subgroups.