Predictive Posterior Power for Sample Size Re-estimation
Creative Commons CC BY 4.0
Information before unblinding regarding the success of confirmatory clinical trials is highly uncertain. Estimates of expected future power which purport to use this information for purposes of sample size adjustment after given interim points need to reflect this uncertainty. Estimates of future power at later interim points need to track the evolution of the clinical trial. We employ sequential models to describe this evolution. We show that current techniques using point estimates of auxiliary parameters for estimating expected power: (i) fail to describe the range of likely power obtained after the anticipated data are observed, (ii) fail to adjust to different kinds of thresholds, and (iii) fail to adjust to the changing patient population. Our algorithms address each of these shortcomings. We show that the uncertainty arising from clinical trials is characterized by filtering later auxiliary parameters through their earlier counterparts and employing the resulting posterior distribution to estimate power. We devise MCMC-based algorithms to implement sample size adjustments after the first interim point. Bayesian models are designed to implement these adjustments in settings where both hard and soft thresholds for distinguishing the presence of treatment effects are present. Sequential MCMC-based algorithms are devised to implement accurate sample size adjustments for multiple interim points. We apply these suggested algorithms to a depression trial for purposes of illustration.