A new design for phase II single-arm clinical trials: Bayesian predictive sample size selection design.

Abstract

6576 Background: The aim of phase II trials is to determine if a new treatment is promising for further testing in confirmatory clinical trials. Most phase II 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 PSSD, predictive sample size selection design (Statistics in Medicine 2012;31:4243-4254). Methods: The design allows for sample size selection followed by any planned interim analyses for early stopping of a trial, together with sample size determination before starting the trial. In the PSSD, we determined the sample size using the 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, we provide two sample sizes, that is, N and Nmax, using two types of design priors. At each interim analysis, we calculate the predictive probability of achieving a successful result at the end of the trial using analysis prior in order to stop the trial in case of low or high efficacy, and we select an optimal sample size, that is, either N or Nmax as needed, on the basis of the predictive probabilities. Results: We investigated the operating characteristics through simulation studies, and the PSSD retrospectively applies to a lung cancer clinical trial. As the number of interim looks increases, the probability of type I errors slightly decreases, and that of type II errors increases. The type I error probabilities of the probabilities of the proposed PSSD are almost similar to those of the non-adaptive design. The type II error probabilities in the PSSD are between those of the two fixed sample size (N or Nmax) designs. Conclusions: From a practical standpoint, the proposed design could be useful in phase II single-arm clinical trials with a binary endpoint. In the near future, this approach will be implemented in actual clinical trials to assess its usefulness and to extend it to more complicated clinical trials.