A parsimonious personalized dose-finding model via dimension reduction

DOI10.48550/ARXIV.1802.06156zbMATH Open1478.62352OpenAlexW2897519621MaRDI QIDQ101644FDOQ101644

Authors Wenzhuo Zhou, Ruoqing Zhu, Donglin Zeng, Wenzhuo Zhou, Ruoqing Zhu, Donglin Zeng 

Publication date 16 February 2018

Published in Biometrika (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1802.06156

zbMATH Keywords

dimension reductionpropensity scoredirect learningindividualized dose rulesemiparametric inferenceStiefel manifold

Mathematics Subject Classification ID

Nonparametric regression and quantile regression (62G08) Applications of statistics to biology and medical sciences; meta analysis (62P10)

Abstract: Learning an individualized dose rule in personalized medicine is a challenging statistical problem. Existing methods often suffer from the curse of dimensionality, especially when the decision function is estimated nonparametrically. To tackle this problem, we propose a dimension reduction framework that effectively reduces the estimation to a lower-dimensional subspace of the covariates. We exploit that the individualized dose rule can be defined in a subspace spanned by a few linear combinations of the covariates, leading to a more parsimonious model. The proposed framework does not require the inverse probability of the propensity score under observational studies due to a direct maximization of the value function. This distinguishes us from the outcome weighted learning framework, which also solves decision rules directly. Under the same framework, we further propose a pseudo-direct learning approach that focuses more on estimating the dimensionality-reduced subspace of the treatment outcome. Parameters in both approaches can be estimated efficiently using an orthogonality constrained optimization algorithm on the Stiefel manifold. Under mild regularity assumptions, the results on the asymptotic normality of the proposed estimators are established, respectively. We also derive the consistency and convergence rate for the value function under the estimated optimal dose rule. We evaluate the performance of the proposed approaches through extensive simulation studies and a warfarin pharmacogenetic dataset.

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Cited in

(4)

• Statistical Learning for Individualized Asset Allocation
• A Single-Index Model With a Surface-Link for Optimizing Individualized Dose Rules
• orthoDr
• Patient‐Specific Dose Finding Based on Bivariate Outcomes and Covariates

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