Flexible selection of a single treatment incorporating short-term endpoint information in a phase II/III clinical trial

Stallard, N., Kunz, C. U., Todd, S. ORCID: https://orcid.org/0000-0002-9981-923X, Parsons, N. and Friede, T. (2015) Flexible selection of a single treatment incorporating short-term endpoint information in a phase II/III clinical trial. Statistics in Medicine, 34 (23). pp. 3104-3115. ISSN 0277-6715 doi: 10.1002/sim.6567

Abstract/Summary

Seamless phase II/III clinical trials in which an experimental treatment is selected at an interim analysis have been the focus of much recent research interest. Many of the methods proposed are based on the group sequential approach. This paper considers designs of this type in which the treatment selection can be based on short-term endpoint information for more patients than have primary endpoint data available. We show that in such a case, the familywise type I error rate may be inflated if previously proposed group sequential methods are used and the treatment selection rule is not specified in advance. A method is proposed to avoid this inflation by considering the treatment selection that maximises the conditional error given the data available at the interim analysis. A simulation study is reported that illustrates the type I error rate inflation and compares the power of the new approach with two other methods: a combination testing approach and a group sequential method that does not use the short-term endpoint data, both of which also strongly control the type I error rate. The new method is also illustrated through application to a study in Alzheimer's disease. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/40631
Identification Number/DOI	10.1002/sim.6567
Refereed	Yes
Divisions	Science > School of Mathematical, Physical and Computational Sciences > Department of Mathematics and Statistics Science > School of Mathematical, Physical and Computational Sciences > Department of Mathematics and Statistics > Applied Statistics
Uncontrolled Keywords	adaptive design;conditional error;error rate control;multiple testing;sequential clinical trial
Publisher	Wiley
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