Personalized Dose Finding Using Outcome Weighted Learning

Guanhua Chen, Donglin Zeng and Michael R. Kosorok

Journal of the American Statistical Association, 2016, vol. 111, issue 516, 1509-1521

Abstract: In dose-finding clinical trials, it is becoming increasingly important to account for individual-level heterogeneity while searching for optimal doses to ensure an optimal individualized dose rule (IDR) maximizes the expected beneficial clinical outcome for each individual. In this article, we advocate a randomized trial design where candidate dose levels assigned to study subjects are randomly chosen from a continuous distribution within a safe range. To estimate the optimal IDR using such data, we propose an outcome weighted learning method based on a nonconvex loss function, which can be solved efficiently using a difference of convex functions algorithm. The consistency and convergence rate for the estimated IDR are derived, and its small-sample performance is evaluated via simulation studies. We demonstrate that the proposed method outperforms competing approaches. Finally, we illustrate this method using data from a cohort study for warfarin (an anti-thrombotic drug) dosing. Supplementary materials for this article are available online.

Date: 2016
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DOI: 10.1080/01621459.2016.1148611

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