Individualized treatment regimens under correlated data with multiple outcomes

Abstract

Precision medicine involves developing individualized treatment regimes (ITRs) which allow for treatment decisions to be tailored to patient characteristics. Naturally, the identification of the optimal regime, that is, the rule which maximizes patient outcomes, is of interest. Several procedures for estimating optimal ITRs from observational data have been proposed; however, relatively few methods exist for estimating optimal ITRs in the presence of competing risks. Previous approaches either target one particular cause of failure, or rely on singly-robust estimators. We propose a novel doubly-robust regression-based method for estimating optimal ITRs which accounts for the uncertainty related to the unobserved cause of failure by averaging over all possible causes, or targeting the most likely cause. Our approach is straightforward to implement, and we demonstrate an extension to incorporate clustering, motivated by the question of for whom kidney transplantation with hepatitis C virus (HCV)-positive donors is safe, using data from the Organ Procurement and Transplantation Network. Our analysis suggests that a large portion of HCV-negative kidney recipients would see their overall survival unchanged if they were instead provided a kidney from an HCV-positive donor. The estimated treatment rules could be used to provide more efficient allocation of HCV-positive kidneys, increasing the donor pool.