Design, data monitoring, and analysis of clinical trials with co-primary endpoints: A review

ABSTRACT

We review the design, data monitoring, and analyses of clinical trials with co-primary endpoints. Recently developed methods for fixed-sample and group-sequential settings are described. Practical considerations are discussed, and guidance for the application of these methods is provided.

KEYWORDS:

• Co-primary endpoints (CPE)
• fixed-sample designs
• group-sequential designs
• intersection–union test (IUT)
• multiple primary endpoints (MPE)
• type II error adjustment

Acknowledgments

The authors are indebted to Dr. Alex Dmitrienko for inviting us to contribute this paper to the Journal of Biopharmaceutical Statistics. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding

Research reported in this publication was partially supported by the Japan Agency for Medical Research and Development under the Project Promoting Clinical Trials for Development of New Drugs 17lk0201061h0002 and 17lk0201061h0202, and the National Institute of Allergy and Infectious Diseases under Award Numbers UM1AI104681 and UM1AI068634.

Additional information

Funding

Research reported in this publication was partially supported by the Japan Agency for Medical Research and Development under the Project Promoting Clinical Trials for Development of New Drugs 17lk0201061h0002 and 17lk0201061h0202, and the National Institute of Allergy and Infectious Diseases under Award Numbers UM1AI104681 and UM1AI068634.