Machine learning approaches to evaluate heterogeneous treatment effects in randomized controlled trials: a scoping review

BACKGROUND AND OBJECTIVES: Estimating heterogeneous treatment effects (HTEs) in randomized controlled trials (RCTs) has received substantial attention recently. This has led to the development of several statistical and machine learning (ML) algorithms to assess HTEs through identifying individualized treatment effects. However, a comprehensive review of these algorithms is lacking. We thus aimed to catalog and outline currently available statistical and ML methods for identifying HTEs via effect modeling using clinical RCT data and summarize how they have been applied in practice. STUDY DESIGN AND SETTING: We performed a scoping review using prespecified search terms in MEDLINE and Embase, aiming to identify studies that assessed HTEs using advanced statistical and ML methods in RCT data published from 2010 to 2022. RESULTS: Among a total of 32 studies identified in the review, 17 studies applied existing algorithms to RCT data, and 15 extended existing algorithms or proposed new algorithms. Applied algorithms included penalized regression, causal forest, Bayesian causal forest, and other metalearner frameworks. Of these methods, causal forest was the most frequently used (7 studies) followed by Bayesian causal forest (4 studies). Most applications were in cardiology (6 studies), followed by psychiatry (4 studies). We provide example R codes in simulated data to illustrate how to implement these algorithms. CONCLUSION: This review identified and outlined various algorithms currently used to identify HTEs and individualized treatment effects in RCT data. Given the increasing availability of new algorithms, analysts should carefully select them after examining model performance and considering how the models will be used in practice.