Treatment Heterogeneity for Survival Outcomes

TL;DR

This paper reviews and guides the application of metalearners for estimating treatment heterogeneity in survival outcomes, supported by simulations and real data reanalysis, and introduces an R package for implementation.

Contribution

It provides a comprehensive summary, practical guidance, and an R package for applying metalearners to estimate treatment heterogeneity in survival data from RCTs.

Findings

Simulation study shows varying performance based on data complexity

Reanalysis questions the validity of previously identified effect modifiers

Provides practical recommendations for causal inference in survival analysis

Abstract

Estimation of conditional average treatment effects (CATEs) plays an essential role in modern medicine by informing treatment decision-making at a patient level. Several metalearners have been proposed recently to estimate CATEs in an effective and flexible way by re-purposing predictive machine learning models for causal estimation. In this chapter, we summarize the literature on metalearners and provide concrete guidance for their application for treatment heterogeneity estimation from randomized controlled trials' data with survival outcomes. The guidance we provide is supported by a comprehensive simulation study in which we vary the complexity of the underlying baseline risk and CATE functions, the magnitude of the heterogeneity in the treatment effect, the censoring mechanism, and the balance in treatment assignment. To demonstrate the applicability of our findings, we reanalyze the data from the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. While recent literature reports the existence of heterogeneous effects of intensive blood pressure treatment with multiple treatment effect modifiers, our results suggest that many of these modifiers may be spurious discoveries. This chapter is accompanied by survlearners, an R package that provides well-documented implementations of the CATE estimation strategies described in this work, to allow easy use of our recommendations as well as the reproduction of our numerical study.