Imputation-Based Q-Learning for Optimizing Dynamic Treatment Regimes with Right-Censored Survival Outcome

Author:

Lyu Lingyun1,Cheng Yu12ORCID,Wahed Abdus S.3ORCID

Affiliation:

1. Department of Biostatistics, University of Pittsburgh , Pittsburgh, Pennsylvania , USA

2. Department of Statistics, University of Pittsburgh , Pittsburgh, Pennsylvania , USA

3. Departments of Biostatistics and Computational Biology, University of Rochester , Rochester, New York , USA

Abstract

Abstract Q-learning has been one of the most commonly used methods for optimizing dynamic treatment regimes (DTRs) in multistage decision-making. Right-censored survival outcome poses a significant challenge to Q-Learning due to its reliance on parametric models for counterfactual estimation which are subject to misspecification and sensitive to missing covariates. In this paper, we propose an imputation-based Q-learning (IQ-learning) where flexible nonparametric or semiparametric models are employed to estimate optimal treatment rules for each stage and then weighted hot-deck multiple imputation (MI) and direct-draw MI are used to predict optimal potential survival times. Missing data are handled using inverse probability weighting and MI, and the nonrandom treatment assignment among the observed is accounted for using a propensity-score approach. We investigate the performance of IQ-learning via extensive simulations and show that it is more robust to model misspecification than existing Q-Learning methods, imputes only plausible potential survival times contrary to parametric models and provides more flexibility in terms of baseline hazard shape. Using IQ-learning, we developed an optimal DTR for leukemia treatment based on a randomized trial with observational follow-up that motivated this study.

Funder

Patient-Centered Outcomes Research Institute

Publisher

Oxford University Press (OUP)

Subject

Applied Mathematics,General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,Statistics and Probability

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