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Personalized Dose Finding Using Outcome Weighted Learning

delete2017-01-04
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OA
AI
G
Guanhua Chen
Donglin Zeng cover
Donglin Zeng (Donglin Zeng)
M
Michael R. Kosorok *
DOI:10.1080/01621459.2016.1148611delete
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Abstract

Abstract

En 中文
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.
Keywords:
DC algorithm
Dose finding
Individualized dose rule
Risk bound
Weighted support vector regression

Journal

J
Journal of the American Statistical Association
IF:
3
Papers:
5.2K
Citations:
4.8W

Organization

U
university of north carolina
Scholars:
7.4W
Papers: 6.5W
Citations: 93
V
vanderbilt university
Scholars:
5.1W
Papers: 4.1W
Citations: 59
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