Multi-Study R-Learner for Estimating Heterogeneous Treatment Effects Across Studies Using Statistical Machine Learning

Abstract: Estimating heterogeneous treatment effects (HTEs) is crucial for precision medicine. While multiple studies can improve the generalizability of results, leveraging them for estimation is statistically challenging. Existing approaches often assume identical HTEs across studies, but this may be violated due to various sources of between-study heterogeneity, including differences in study design, study populations, and data collection protocols, among others. To this end, we propose a framework for multi-study HTE estimation that accounts for between-study heterogeneity in the nuisance functions and treatment effects. Our approach, the multi-study R-learner, extends the R-learner to obtain principled statistical estimation with ML in the multi-study setting. It involves a data-adaptive objective function that links study-specific treatment effects with nuisance functions through membership probabilities, which enable information to be borrowed across potentially heterogeneous studies. The multi-study R-learner framework can combine data from randomized controlled trials, observational studies, or a combination of both. It's easy to implement and flexible in its ability to incorporate ML for estimating HTEs, nuisance functions, and membership probabilities. In the series estimation framework, we show that the multi-study R-learner is asymptotically normal and more efficient than the R-learner when there is between-study heterogeneity in the propensity score model under homoscedasticity. We illustrate using cancer data that the proposed method performs favorably compared to existing approaches in the presence of between-study heterogeneity.