Resampling-based methods for the analysis of multiple endpoints in clinical trials

We consider multivariate tests for comparing two treatments with multiple e ndpoints. The test decision is drawn from the simultaneous consideration of the univariate tests for the single endpoints. A general class of these te sts, called cut-off tests, can be given, which, however, can lead to highly conservative procedures because the dependencies among the endpoints are n ot taken into account. In applying resampling-based methods considerable im provements for these tests can be achieved. Resampling-based cut-off tests are proposed which are sensitive against a treatment difference in a single endpoint, in a subgroup of endpoints, or in all endpoints, The results of Monte Carlo simulations demonstrate that a remarkable gain in statistical p ower as compared to the crude simultaneous consideration can be reached. In particular, for the multivariate one-sided test situation the proposed tes ts can be recommended. As an example the application of the tests is demons trated by data from a clinical trial. Copyright (C) 1999 John Wiley & Sons, Ltd.