Personalized Dose Finding Using Outcome Weighted Learning.

TitlePersonalized Dose Finding Using Outcome Weighted Learning.
Publication TypeJournal Article
Year of Publication2016
AuthorsChen, Guanhua, Donglin Zeng, and Michael R. Kosorok
JournalJ Am Stat Assoc
Volume111
Issue516
Pagination1509-1521
Date Published2016
ISSN0162-1459
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 paper, 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.

DOI10.1080/01621459.2016.1148611
Alternate JournalJ Am Stat Assoc
Original PublicationPersonalized dose finding using outcome weighted learning.
PubMed ID28255189
PubMed Central IDPMC5327863
Grant ListR01 CA082659 / CA / NCI NIH HHS / United States
R01 GM047845 / GM / NIGMS NIH HHS / United States
R01 NS073671 / NS / NINDS NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
U01 NS082062 / NS / NINDS NIH HHS / United States