A scoping review of studies using observational data to optimise dynamic treatment regimens

Robert K Mahar,Bibhas Chakraborty,Myra B Mcguinness,Maarten J Ijzerman,Julie A Simpson,John B Carlin

doi:10.1186/s12874-021-01211-2

Abstract

BackgroundDynamic treatment regimens (DTRs) formalise the multi-stage and dynamic decision problems that clinicians often face when treating chronic or progressive medical conditions. Compared to randomised controlled trials, using observational data to optimise DTRs may allow a wider range of treatments to be evaluated at a lower cost. This review aimed to provide an overview of how DTRs are optimised with observational data in practice.MethodsUsing the PubMed database, a scoping review of studies in which DTRs were optimised using observational data was performed in October 2020. Data extracted from eligible articles included target medical condition, source and type of data, statistical methods, and translational relevance of the included studies.ResultsFrom 209 PubMed abstracts, 37 full-text articles were identified, and a further 26 were screened from the reference lists, totalling 63 articles for inclusion in a narrative data synthesis. Observational DTR models are a recent development and their application has been concentrated in a few medical areas, primarily HIV/AIDS (27, 43%), followed by cancer (8, 13%), and diabetes (6, 10%). There was substantial variation in the scope, intent, complexity, and quality between the included studies. Statistical methods that were used included inverse-probability weighting (26, 41%), the parametric G-formula (16, 25%), Q-learning (10, 16%), G-estimation (4, 6%), targeted maximum likelihood/minimum loss-based estimation (4, 6%), regret regression (3, 5%), and other less common approaches (10, 16%). Notably, studies that were primarily intended to address real-world clinical questions (18, 29%) tended to use inverse-probability weighting and the parametric G-formula, relatively well-established methods, along with a large amount of data. Studies focused on methodological developments (45, 71%) tended to be more complicated and included a demonstrative real-world application only.ConclusionsAs chronic and progressive conditions become more common, the need will grow for personalised treatments and methods to estimate the effects of DTRs. Observational DTR studies will be necessary, but so far their use to inform clinical practice has been limited. Focusing on simple DTRs, collecting large and rich clinical datasets, and fostering tight partnerships between content experts and data analysts may result in more clinically relevant observational DTR studies.

Highlights

Dynamic treatment regimens (DTRs) formalise the multi-stage and dynamic decision problems that clinicians often face when treating chronic or progressive medical conditions
As chronic and progressive conditions become more common, the need will grow for personalised treatments and methods to estimate the effects of DTRs
This study provides a scoping review [16] to systematically map how observational data have been used to estimate the value of DTRs in practice with the following specific aims:

Summary

Introduction

Dynamic treatment regimens (DTRs) formalise the multi-stage and dynamic decision problems that clinicians often face when treating chronic or progressive medical conditions. Dynamic treatment regimens (or regimes) (DTRs) formalise the multi-stage and dynamic decision problems clinicians often face when treating chronic or progressive conditions [1–5]. A DTR can be defined using decision rules, functions that map each patient’s accumulated clinical and treatment history to the subsequent treatment at each treatment decision point. These rules are typically derived from parametric models. In order for the estimated treatment effects that inform the decision rules to have a causal interpretation, a number of conditions must be met, which are summarised

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Conclusion