A Rank-Sum-Type Test for Paired Data with Multiple Endpoints

Clinical trials and other types of studies often examine the effects of a particular treatment or experimental condition on a number of different response variables. Although the usual approach for analysing such data is to examine each variable separately, this can increase the chance of false positive findings. Bonferroni's inequality or Hotelling's T2 statistic can be employed to control the overall type I error rate, but these tests generally lack power for alternatives in which the treatment improves the outcome on most or all of the endpoints. For the comparison of independent groups, O'Brien (1984) developed a rank-sum type test that has greater power than the Bonferroni and T2 procedures when one treatment is uniformly better (i.e. for all endpoints) than the other treatment(s). In this paper we adapt the rank-sum test to studies involving paired data and demonstrate that it, too, has power advantages for such alternatives. Simulation results are described, and an example from a study measuring the effects of sleep loss on glucose metabolism is presented to illustrate the methodology.