Sample Size Reestimation for Confirmatory Clinical Trials

Chapter
Part of the Applied Bioinformatics and Biostatistics in Cancer Research book series (ABB)

Abstract

This chapter discusses the benefits and limitations of adaptive sample size reestimation for phase 3 confirmatory clinical trials. Comparisons are made with more traditional fixed sample and group sequential designs. It is seen that the real benefit of the adaptive approach arises through the ability to invest sample size resources into the trial in stages. The trial starts with a small up-front sample size commitment. Additional sample size resources are committed to the trial only if promising results are obtained at an interim analysis. This strategy is seen to be more advantageous than the fixed sample or group sequential approaches in certain settings. The discussion is illustrated with the help of three case studies of actual adaptive trials, one in neurology with a continuous endpoint and one in cardiology with a binomial endpoint, and one in oncology with a time to event endpoint. Methodological, regulatory and operational issues are examined.

Keywords

Placebo Schizophrenia Stake 

Notes

Acknowledgements

The author thanks Dr. Howie Golub for helpful discussions on adaptive designs and Dave Harrington for critical comments that have greatly improved the article.

Software support for this article was provided by the East (2008) software package developed by Cytel Corporation.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Cytel Corporation and Harvard School of Public HealthCambridgeUSA

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