Nonparametric estimation of an optimal treatment rule with fused randomized trials and missing effect modifiers

TL;DR

This paper introduces a nonparametric method to estimate optimal personalized treatment rules by combining data from multiple randomized trials with differing covariate sets, aiming to improve individualized treatment decisions.

Contribution

It proposes a novel nonparametric estimator for dynamic treatment rules that effectively fuses data across trials with mismatched covariates, enhancing personalized medicine.

Findings

Successfully applied to opioid treatment trials

Estimated treatment rules reducing relapse risk

Demonstrated improved personalization over standard methods

Abstract

A fundamental principle of clinical medicine is that a treatment should only be administered to those patients who would benefit from it. Treatment strategies that assign treatment to patients as a function of their individual characteristics are known as dynamic treatment rules. The dynamic treatment rule that optimizes the outcome in the population is called the optimal dynamic treatment rule. Randomized clinical trials are considered the gold standard for estimating the marginal causal effect of a treatment on an outcome; they are often not powered to detect heterogeneous treatment effects, and thus, may rarely inform more personalized treatment decisions. The availability of multiple trials studying a common set of treatments presents an opportunity for combining data, often called data-fusion, to better estimate dynamic treatment rules. However, there may be a mismatch in the set of patient covariates measured across trials. We address this problem here; we propose a nonparametric estimator for the optimal dynamic treatment rule that leverages information across the set of randomized trials. We apply the estimator to fused randomized trials of medications for the treatment of opioid use disorder to estimate a treatment rule that would match patient subgroups with the medication that would minimize risk of return to regular opioid use.