Some Multiplicity Adjustment Procedures for Clinical Trials with Sequential Design and Multiple Endpoints

Abstract

This article proposes some new multiplicity adjustment procedures for clinical trials with multiple endpoints and multiple interim analyses. The proposed sequential procedures, adapting the popular multiple comparison procedures for fixed time-point design and using α-spending for each endpoint, are shown to strongly control the family-wise Type-1 error rate and provide powerful yet versatile multiplicity adjustment solutions for monitoring multiple endpoints via interim analyses.

KEYWORDS:

• Generalized Simes inequality
• Group-sequential p-values
• Multiplicity
• q-values
• early submission
• α-propagation

Acknowledgments

The authors thank the anonymous referees and the Associate Editor for their helpful comments and suggestions, which have greatly improved this article.

Disclosure Statement

Both authors are Sanofi employees and may hold shares and/or stock options in the company.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.