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通过凹融合探索异质性治疗效果

Exploration of Heterogeneous Treatment Effects via Concave Fusion.

作者信息

Ma Shujie, Huang Jian, Zhang Zhiwei, Liu Mingming

机构信息

Department of Statistics, University of California at Riverside, Riverside, California 92521, USA.

Department of Statistics and Actuarial Science, University of Iowa, Iowa City, USA.

出版信息

Int J Biostat. 2019 Sep 20;16(1):ijb-2018-0026. doi: 10.1515/ijb-2018-0026.

Abstract

Understanding treatment heterogeneity is essential to the development of precision medicine, which seeks to tailor medical treatments to subgroups of patients with similar characteristics. One of the challenges of achieving this goal is that we usually do not have a priori knowledge of the grouping information of patients with respect to treatment effect. To address this problem, we consider a heterogeneous regression model which allows the coefficients for treatment variables to be subject-dependent with unknown grouping information. We develop a concave fusion penalized method for estimating the grouping structure and the subgroup-specific treatment effects, and derive an alternating direction method of multipliers algorithm for its implementation. We also study the theoretical properties of the proposed method and show that under suitable conditions there exists a local minimizer that equals the oracle least squares estimator based on a priori knowledge of the true grouping information with high probability. This provides theoretical support for making statistical inference about the subgroup-specific treatment effects using the proposed method. The proposed method is illustrated in simulation studies and illustrated with real data from an AIDS Clinical Trials Group Study.

摘要

理解治疗异质性对于精准医学的发展至关重要,精准医学旨在为具有相似特征的患者亚组量身定制医疗治疗方案。实现这一目标的挑战之一在于,我们通常对于患者在治疗效果方面的分组信息没有先验知识。为解决这个问题,我们考虑一种异质性回归模型,该模型允许治疗变量的系数依赖于个体且分组信息未知。我们开发了一种凹融合惩罚方法来估计分组结构和亚组特异性治疗效果,并推导了一种交替方向乘子算法来实现它。我们还研究了所提方法的理论性质,并表明在合适的条件下,存在一个局部极小值点,它以高概率等于基于真实分组信息先验知识的神谕最小二乘估计量。这为使用所提方法对亚组特异性治疗效果进行统计推断提供了理论支持。所提方法在模拟研究中得到了说明,并通过艾滋病临床试验组研究的真实数据进行了展示。

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