Ranking of average treatment effects with generalized random forests for time‐to‐event outcomes

• Published in: Statistics in medicine Vol. 42; no. 10; pp. 1542 - 1564
• Main Authors: Rytgaard, Helene C. W., Ekstrøm, Claus T., Kessing, Lars V., Gerds, Thomas A.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 10.05.2023; Wiley Subscription Services, Inc
• Subjects: average treatment effect; Clinical outcomes; competing risks; Drug therapy; Humans; Probability; Random Forest; random forests; Statistical analysis; Statistical methods; time‐to‐event; competing risks; time-to-event; random forests; average treatment effect
• ISSN: 0277-6715; 1097-0258
• DOI: 10.1002/sim.9686

Linkage between drug claims data and clinical outcome allows a data‐driven experimental approach to drug repurposing. We develop an estimation procedure based on generalized random forests for estimation of time‐point specific average treatment effects in a time‐to‐event setting with competing risks. To handle right‐censoring, we propose a two‐step procedure for estimation, applying inverse probability weighting to construct time‐point specific weighted outcomes as input for the generalized random forest. The generalized random forests adaptively handle covariate effects on the treatment assignment by applying a splitting rule that targets a causal parameter. Using simulated data we demonstrate that the method is effective for a causal search through a list of treatments to be ranked according to the magnitude of their effect on clinical outcome. We illustrate the method using the Danish national health registries where it is of interest to discover drugs with an unexpected protective effect against relapse of severe depression.