Weighted Statistics for Testing Multiple Endpoints in Clinical Trials

Abstract

Bonferroni, Holm, and Holm-type stepwise approaches have been well developed for the simultaneous testing of multiple hypotheses in medical experiments. Methods exist for controlling familywise error rates at their preset levels. This article shows how performance of these tests can often be substantially improved by accounting for the relative difficulty of tests. Introducing suitably chosen weights optimizes the error spending between the multiple endpoints. Such an extension of classical testing schemes generally results in a smaller required sample size without sacrificing the familywise error rate and power.