The analysis of multiple endpoints in clinical trials

Abstract

Treatment comparisons in randomized clinical trials usually involve several endpoints such that conventional significance testing can seriously inflate the overall Type I error rate. One option is to select a single primary endpoint for formal statistical inference, but this is not always feasible. Another approach is to apply Bonferroni correction (i.e., multiply each P-value by the total number of endpoints). Its conservatism for correlated endpoints is examined for multivariate normal data. A third approach is to derive an appropriate global test statistic and this paper explores one such test applicable to any set of asymptotically normal test statistics. Quantitative, binary, and survival endpoints are all considered within this general framework. Two examples are presented and the relative merits of the proposed strategies are discussed.