Adaptive platform trials: the impact of common controls on type one error and power

Nguyen Q, Hees K, Hofner B (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Journal of Biopharmaceutical Statistics Taylor & Francis: STM, Behavioural Science and Public Health Titles / Taylor & Francis

DOI: 10.1080/10543406.2023.2275765

Abstract

Platform trials offer a framework to study multiple interventions in one trial with the opportunity of opening and closing arms. The use of common controls can increase efficiency as compared to individual controls. The need for multiplicity adjustment because of common controls is currently a debate among researchers, pharmaceutical companies, and regulators. The impact of common controls on the type one error in a fixed platform trial, i.e. when all treatments start and end recruitment at the same time, has been discussed in the literature before. We complement these findings by investigating the impact of a common control on the type one error and power in a flexible platform trial, i.e. when one arm joins the platform later. We derived the correlation of test statistics to assess the impact of the overlap and compared the results to a trial with individual controls. Furthermore, we evaluate the power, and the impact of multiplicity adjustment on the power in fixed and flexible platform trials. These methodological considerations are complemented by a regulatory guideline review. With multiple arms, the FWER is inflated when no multiplicity adjustment is applied. However, the FWER inflation is smaller with common controls than with individual controls. Even after multiplicity adjustment, a trial with common controls is often beneficial in terms of sample size and power. However, in some cases, the trial with common controls loses the efficiency gain and it might be advisable to run a separate trial rather than joining a platform trial.

Authors with CRIS profile

Benjamin Hofner

Involved external institutions

Paul Ehrlich Institute / Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel (PEI)

Germany (DE)

How to cite

APA:

Nguyen, Q., Hees, K., & Hofner, B. (2023). Adaptive platform trials: the impact of common controls on type one error and power. Journal of Biopharmaceutical Statistics. https://dx.doi.org/10.1080/10543406.2023.2275765

MLA:

Nguyen, Quynh, Katharina Hees, and Benjamin Hofner. "Adaptive platform trials: the impact of common controls on type one error and power." Journal of Biopharmaceutical Statistics (2023).

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