Selection of the treatment effect for sample size determination in a superiority clinical trial using a hybrid classical and Bayesian procedure

Contemp Clin Trials. 2015 Mar:41:160-71. doi: 10.1016/j.cct.2015.01.002. Epub 2015 Jan 9.

Abstract

Specification of the treatment effect that a clinical trial is designed to detect (θA) plays a critical role in sample size and power calculations. However, no formal method exists for using prior information to guide the choice of θA. This paper presents a hybrid classical and Bayesian procedure for choosing an estimate of the treatment effect to be detected in a clinical trial that formally integrates prior information into this aspect of trial design. The value of θA is found that equates the pre-specified frequentist power and the conditional expected power of the trial. The conditional expected power averages the traditional frequentist power curve using the conditional prior distribution of the true unknown treatment effect θ as the averaging weight. The Bayesian prior distribution summarizes current knowledge of both the magnitude of the treatment effect and the strength of the prior information through the assumed spread of the distribution. By using a hybrid classical and Bayesian approach, we are able to formally integrate prior information on the uncertainty and variability of the treatment effect into the design of the study, mitigating the risk that the power calculation will be overly optimistic while maintaining a frequentist framework for the final analysis. The value of θA found using this method may be written as a function of the prior mean μ0 and standard deviation τ0, with a unique relationship for a given ratio of μ0/τ0. Results are presented for Normal, Uniform, and Gamma priors for θ.

Keywords: Clinical trial; Clinically relevant difference; Hybrid classical–Bayesian; Sample size; Treatment effect.

MeSH terms

  • Bayes Theorem
  • Clinical Trials as Topic*
  • Humans
  • Sample Size*
  • Statistics as Topic*