Assessing the hierarchical beta-binomial model as a basic information sharing tool in basket trials

Abstract

ABSTRACT The majority of statistical methods to share information in basket trials are based on a Bayesian hierarchical model with a common normal distribution for the logit-transformed response rates. The methods are of varying complexity, yet they all use this basic model. Generally, complexity is an obstacle for the application in clinical trials and that includes the use of the logit-transformation. The transformation complicates the model and impedes a direct interpretation of the hyperparameters. On the other hand, there exist basket trial designs which directly work on the probability scale of the response rate which facilitates the understanding of the model for many stakeholders. In order to reduce unnecessary complexity, we considered using a hierarchical beta-binomial model instead of the transformed models. This article investigates whether this approach is a practicable alternative to the commonly applied sharing tools based on a logit-transformation of the response rates. For this purpose, we performed a systematic comparison of the two models, starting with the distributional assumptions for the response rates, continuing with the Bayesian behavior together with binomial data in an independent setting and ended with a simulation study for the hierarchical model under various data and prior scenarios. All Bayesian comparisons require equal starting points, wherefore we propose a calibration procedure to choose similar priors for the models. The evaluation of the sharing property additionally required an evaluation measure for simulation results, which we derived in this work. The conclusion of the comparison is that the hierarchical beta-binomial model is a feasible alternative basic model to share information in basket trials.