Article first published online: 25 APR 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Statistics in Medicine
Volume 31, Issue 20, pages 2151–2168, 10 September 2012
How to Cite
Wang, B. and Cui, X. (2012), A new partition testing strategy for multiple endpoints. Statist. Med., 31: 2151–2168. doi: 10.1002/sim.5366
- Issue published online: 16 AUG 2012
- Article first published online: 25 APR 2012
- Manuscript Accepted: 17 FEB 2012
- Manuscript Received: 22 DEC 2010
- multiple endpoints;
- likelihood ratio test;
- partition testing;
- union-intersection test
To evaluate efficacy in multiple endpoints in confirmatory clinical trials is a challenging problem in multiple hypotheses testing. The difficulty comes from the different importance of each endpoint and their underlying correlation. Current approaches to this problem, which test the efficacy in certain dose–endpoint combinations and collate the results, are based on closed testing or partition testing. Despite their different formulations, all current approaches test their dose–endpoint combinations as intersection hypotheses and apply various union-intersection tests. Likelihood ratio test is seldom used owing to the extensive computation and lack of consistent inferences.
In this article, we first generalize the formulation of multiple endpoints problem to include the cases of alternative primary endpoints and co-primary endpoints. Then we propose a new partition testing approach that is based on consonance-adjusted likelihood ratio test. The new procedure provides consistent inferences, and yet, it is still conservative and does not rely on the estimation of endpoint correlation or independence assumptions that might be challenged by regulatory agencies. Copyright © 2012 John Wiley & Sons, Ltd.