A likely responder approach for the analysis of randomized controlled trials

随机对照试验分析中可能的反应者方法

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Abstract

OBJECTIVE: To further the precision medicine goal of tailoring medical treatment to individual patient characteristics by providing a method of analysis of the effect of test treatment, T, compared to a reference treatment, R, in participants in a RCT who are likely responders to T. METHODS: Likely responders to T are individuals whose expected response at baseline exceeds a prespecified minimum. A prognostic score, the expected response predicted as a function of baseline covariates, is obtained at trial completion. It is a balancing score that can be used to match likely responders randomized to T with those randomized to R; the result is comparable treatment groups that have a common covariance distribution. Treatments are compared based on observed outcomes in this enriched sample. The approach is illustrated in a RCT comparing two treatments for opioid use disorder. RESULTS: A standard statistical analysis of the opioid use disorder RCT found no treatment difference in the total sample. However, a subset of likely responders to T were identified and in this group, T was statistically superior to R. CONCLUSION: The causal treatment effect of T relative to R among likely responders may be more important than the effect in the whole target population. The prognostic score function provides quantitative information to support patient specific treatment decisions regarding T furthering the goal of precision medicine.

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