Propensity score weighted multi-source exchangeability models for incorporating external control data in randomized clinical trials.

Abstract

Among clinical trialists, there has been a growing interest in using external data to improve decision-making and accelerate drug development in randomized clinical trials (RCTs). Here we propose a novel approach that combines the propensity score weighting (PW) and the multi-source exchangeability modelling (MEM) approaches to augment the control arm of a RCT in the rare disease setting. First, propensity score weighting is used to construct weighted external controls that have similar observed pre-treatment characteristics as the current trial population. Next, the MEM approach evaluates the similarity in outcome distributions between the weighted external controls and the concurrent control arm. The amount of external data we borrow is determined by the similarities in pretreatment characteristics and outcome distributions. The proposed approach can be applied to binary, continuous and count data. We evaluate the performance of the proposed PW-MEM method and several competing approaches based on simulation and re-sampling studies. Our results show that the PW-MEM approach improves the precision of treatment effect estimates while reducing the biases associated with borrowing data from external sources.