Estimating the optimal individualized treatment rule from a cost‐effectiveness perspective

Optimal individualized treatment rules (ITRs) provide customized treatment recommendations based on subject characteristics to maximize clinical benefit in accordance with the objectives in precision medicine. As a result, there is growing interest in developing statistical tools for estimating optimal ITRs in evidence‐based research. In health economic perspectives, policy makers consider the tradeoff between health gains and incremental costs of interventions to set priorities and allocate resources. However, most work on ITRs has focused on maximizing the effectiveness of treatment without considering costs. In this paper, we jointly consider the impact of effectiveness and cost on treatment decisions and define ITRs under a composite‐outcome setting, so that we identify the most cost‐effective ITR that accounts for individual‐level heterogeneity through direct optimization. In particular, we propose a decision‐tree–based statistical learning algorithm that uses a net‐monetary‐benefit–based reward to provide nonparametric estimations of the optimal ITR. We provide several approaches to estimating the reward underlying the ITR as a function of subject characteristics. We present the strengths and weaknesses of each approach and provide practical guidelines by comparing their performance in simulation studies. We illustrate the top‐performing approach from our simulations by evaluating the projected 15‐year personalized cost‐effectiveness of the intensive blood pressure control of the Systolic Blood Pressure Intervention Trial (SPRINT) study.