A Bayesian basket trial design accounting for uncertainties of homogeneity and heterogeneity of treatment effect among subpopulations.

Basket trials are a recent and innovative approach in oncological clinical trial design. A basket trial is a type of clinical trial for which eligibility is based on the presence of a specific genomic alteration, irrespective of cancer type. Additionally, basket trials are often used to evaluate the response rate of an investigational therapy across several types of cancer. Recently developed statistical methods for evaluating the response rate in basket trials can be generally categorized into two groups: (a) those that account for the degrees of homogeneity/heterogeneity of response rates among subpopulations, and (b) those using borrowed response rate information across subpopulations to improve the statistical efficiency using Bayesian hierarchical models. In this study, we developed a new basket trial design that accounts for the uncertainties of homogeneity and heterogeneity of response rates among subpopulations using the Bayesian model averaging approach. We demonstrated the utility of the proposed method by comparing our approach against other methods for the two methodological groups using simulated and actual data. On an average, the proposed methods offered an intermediate performance between the BHM-weak and BHM-strong methods. The proposed method would be useful for "signal-finding" basket trials without prior information on the treatment effect of an investigational drug, in part because the proposed method does not require specifications regarding prior distributions of homogeneity response rates among subpopulations.
(© 2020 John Wiley & Sons Ltd.)