Methods in dynamic treatment regimens using observational healthcare data: A systematic review

Abstract

We present a systematic review of methods used to estimate Dynamic Treatment Regimens (DTR) using observational healthcare data and provide a brief summary of their strengths and weaknesses, evaluation metrics, and suitable research problem settings. We considered all observational studies identified in PubMed or EMBASE between January 1950 until January 2022, including only studies that evaluated medical treatments or interventions as exposure and/or outcome in patients and where DTRs were estimated. 83 studies met our inclusion criteria; 44.6% estimating DTR utilizing reinforcement learning, 18.1% utilizing counterfactual-based models, 12.1% utilizing classification-based methods, and 9.6% utilized g-methods. Among the studies analyzed, 28.9% aimed to replicate human expert DTRs, while 71.1% aimed to refine and improve existing DTRs. Approximately two-thirds of studies (65.1%) reported the assumptions required for their applied methods, such as exchangeability, positivity, consistency, and Markov property. Most of the studies (83.1%) estimated DTRs with more than two treatment options; 50.6% mentioned time-varying confounders, only a few estimated conditional average treatment effects (7.2%). Most (85.5%) validated their methods, with 32.5% using expected outcomes (e.g., survival rates), 26.5% employing simulated data, and 25.3% conducting direct comparisons with observational data.