Bayesian Optimal Designs for Multi-Arm Multi-Stage Phase II Randomized Clinical Trials with Multiple Endpoints.

Authors

Guillaume Mulier
Sylvie Chevret
Ruitao Lin
Lucie Biard

Publication Date

1-1-2024

Journal

Statistics in Biopharmaceutical Research

Abstract

There is a growing need to evaluate of multiple competing drugs in phase II trials where the number of patients is often limited, and simultaneous assessment of both efficacy and toxicity is crucial. To avoid the waste of research resources, it is indeed more efficient to screen multiple drugs at once in a platform phase II setting. We aim to adapt the Bayesian optimal phase II (BOP2) design to multi-arm trials for both uncontrolled and controlled settings. The binary efficacy and toxicity endpoints are modeled by a Dirichlet distribution as a vector of four outcomes. Posterior marginal distributions at each analysis are used to derive the monitoring threshold that varies during the trial. We control the family-wise Type I error rate for multiple comparison against a common reference value or a shared control. We conduct simulation studies under both uncontrolled and controlled settings to evaluate the operating characteristics of the proposed design. Our simulations demonstrate that the design exhibits better operating characteristics compared to a design using a constant threshold and is less sensitive to changes in accrual rate relative to what was planned. The design had promising operating characteristics and could be used in phase II oncology clinical trials for evaluating multiple drugs at a time.

Keywords

Bayes, Multi-arm, Oncology, Phase II, Randomization

DOI

10.1080/19466315.2024.2344543

PMID

39301054

PMCID

PMC11412438

PubMedCentral® Posted Date

9-19-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes