Applying Meta-Analytic-Predictive Priors with the R Bayesian Evidence Synthesis Tools

Abstract

Use of historical data in clinical trial design and analysis has shown various advantages such as reduction of number of subjects and increase of study power. The meta-analytic-predictive (MAP) approach accounts with a hierarchical model for between-trial heterogeneity in order to derive an informative prior from historical data. In this paper, we introduce the package RBesT (R Bayesian evidence synthesis tools) which implements the MAP approach with normal (known sampling standard deviation), binomial and Poisson endpoints. The hierarchical MAP model is evaluated by Markov chain Monte Carlo (MCMC). The MCMC samples representing the MAP prior are approximated with parametric mixture densities which are obtained with the expectation maximization algo-rithm. The parametric mixture density representation facilitates easy communication of the MAP prior and enables fast and accurate analytical procedures to evaluate properties of trial designs with informative MAP priors. The paper first introduces the framework of robust Bayesian evidence synthesis in this setting and then explains how RBesT facilitates the derivation and evaluation of an informative MAP prior from historical control data. In addition we describe how the meta-analytic framework relates to further applications including probability of success calculations.