A Bayesian predictive sample size selection design for single-arm exploratory clinical trials.

The aim of an exploratory clinical trial is to determine whether a new intervention is promising for further testing in confirmatory clinical trials. Most exploratory clinical trials are designed as single-arm trials using a binary outcome with or without interim monitoring for early stopping. In this context, we propose a Bayesian adaptive design denoted as predictive sample size selection design (PSSD). The design allows for sample size selection following any planned interim analyses for early stopping of a trial, together with sample size determination before starting the trial. In the PSSD, we determine the sample size using the method proposed by Sambucini (Statistics in Medicine 2008; 27:1199-1224), which adopts a predictive probability criterion with two kinds of prior distributions, that is, an 'analysis prior' used to compute posterior probabilities and a 'design prior' used to obtain prior predictive distributions. In the sample size determination of the PSSD, we provide two sample sizes, that is, N and N(max) , using two types of design priors. At each interim analysis, we calculate the predictive probabilities of achieving a successful result at the end of the trial using the analysis prior in order to stop the trial in case of low or high efficacy (Lee et al., Clinical Trials 2008; 5:93-106), and we select an optimal sample size, that is, either N or N(max) as needed, on the basis of the predictive probabilities. We investigate the operating characteristics through simulation studies, and the PSSD retrospectively applies to a lung cancer clinical trial. (243)