Personalized Dose Finding Using Outcome Weighted Learning

• 成果类型: Article
• 署名作者: Chen, Guanhua; Zeng, Donglin; Kosorok, Michael R.
• 署名单位: Vanderbilt University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill
• 刊物名称: JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
• ISSN/ISSBN: 0162-1459
• DOI: 10.1080/01621459.2016.1148611
• 发表日期: 2016
• 页码: 1509-1521
• 关键词: treatment regimes; treatment rules; RISK; warfarin; regression; inference; TUTORIAL; DRUG

摘要

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.