Liu Pan, Li Jialiang, Kosorok Michael R
Department of Statistics and Data Science, National University of Singapore, Singapore, Singapore.
Duke University NUS Graduate Medical School, Singapore, Singapore.
Stat Methods Med Res. 2023 Apr;32(4):773-788. doi: 10.1177/09622802231154327. Epub 2023 Feb 12.
Central to personalized medicine and tailored therapies is discovering the subpopulations that account for treatment effect heterogeneity and are likely to benefit more from given interventions. In this article, we introduce a change plane model averaging method to identify subgroups characterized by linear combinations of predictive variables and multiple cut-offs. We first fit a sequence of statistical models, each incorporating the thresholding effect of one particular covariate. The estimation of submodels is accomplished through an iterative integration of a change point detection method and numerical optimization algorithms. A frequentist model averaging approach is then employed to linearly combine the submodels with optimal weights. Our approach can deal with high-dimensional settings involving enormous potential grouping variables by adopting the sparsity-inducing penalties. Simulation studies are conducted to investigate the prediction and subgrouping performance of the proposed method, with a comparison to various competing subgroup detection methods. Our method is applied to a dataset from a warfarin pharmacogenetics study, producing some new findings.
个性化医疗和定制疗法的核心是发现那些导致治疗效果异质性且可能从特定干预措施中获益更多的亚群。在本文中,我们引入了一种变化平面模型平均法,以识别由预测变量的线性组合和多个临界值所表征的亚组。我们首先拟合一系列统计模型,每个模型都纳入一个特定协变量的阈值效应。子模型的估计通过变化点检测方法和数值优化算法的迭代整合来完成。然后采用频率主义模型平均法,以最优权重对子模型进行线性组合。我们的方法通过采用稀疏性诱导惩罚,可以处理涉及大量潜在分组变量的高维情况。进行了模拟研究,以调查所提方法的预测和亚组划分性能,并与各种竞争的亚组检测方法进行比较。我们的方法应用于一项华法林药物遗传学研究的数据集,得出了一些新发现。