Propensity score-integrated Bayesian prior approaches for augmented control designs: a simulation study

Abstract

ABSTRACT Drug development can be costly, and the availability of clinical trial participants may be limited either due to the disease setting (rare or pediatric diseases) or due to many sponsors evaluating multiple drugs or combinations in the same patient population. To maximize resource utilization, sponsors may leverage patient-level control data from historical trials. However, in a study with no control arm, it is impossible to evaluate if the historical controls are an appropriate comparator for the current study. Here, instead of conducting a single-arm trial and relying solely on historical controls, we evaluate the situation where a minimal number of patients are enrolled into a control arm, which is augmented by borrowing historical control data. Propensity score (PS) methods are commonly used to minimize bias for non-randomized data. In addition, Bayesian information borrowing with PS adjustments has been proposed when it may not be reasonable to include all available historical data. This paper proposes using PS adjustment integrated with Bayesian commensurate priors to adaptively borrow information. We then evaluate the performance of different PS adjustment methods and different Bayesian priors for augmented control using simulation studies to help inform the design of future trials. In general, we find that propensity weighting or matching combined with the commensurate prior yield reasonable statistical properties across a range of scenarios. Finally, our proposed methods are applied to a real trial with a binary outcome. Abbreviations: PS: propensity score; IPTW: inverse probability of treatment weighting; ATT: average treatment effect on those who received treatment; RCT: randomized controlled trial; CDD: covariate distribution difference; ESS: effective sample size