Estimating the Sampling Distribution of Test-Statistics in Bayesian Clinical Trials

Bayesian inference and the use of posterior or posterior predictive probabilities for decision making have become increasingly popular in clinical trials. The current approach toward Bayesian clinical trials is, however, a hybrid Bayesian-frequentist approach where the design and decision criteria are assessed with respect to frequentist operating characteristics such as power and type I error rate. These operating characteristics are commonly obtained via simulation studies. In this article we propose methodology to utilize large sample theory of the posterior distribution to define simple parametric models for the sampling distribution of the Bayesian test statistics, i.e., posterior tail probabilities. The parameters of these models are then estimated using a small number of simulation scenarios, thereby refining these models to capture the sampling distribution for small to moderate sample size. The proposed approach toward assessment of operating characteristics and sample size determination can be considered as simulation-assisted rather than simulation-based and significantly reduces the computational burden for design of Bayesian trials.