Shen Jincheng, Wang Lu, Daignault Stephanie, Spratt Daniel E, Morgan Todd M, Taylor Jeremy M G
a Department of Population Health Sciences , University of Utah School of Medicine , Salt Lake City , UT , USA.
b Department of Biostatistics , University of Michigan , Ann Arbor , MI , USA.
J Biopharm Stat. 2018;28(2):362-381. doi: 10.1080/10543406.2017.1380036. Epub 2017 Oct 25.
A personalized treatment policy requires defining the optimal treatment for each patient based on their clinical and other characteristics. Here we consider a commonly encountered situation in practice, when analyzing data from observational cohorts, that there are auxiliary variables which affect both the treatment and the outcome, yet these variables are not of primary interest to be included in a generalizable treatment strategy. Furthermore, there is not enough prior knowledge of the effect of the treatments or of the importance of the covariates for us to explicitly specify the dependency between the outcome and different covariates, thus we choose a model that is flexible enough to accommodate the possibly complex association of the outcome on the covariates. We consider observational studies with a survival outcome and propose to use Random Survival Forest with Weighted Bootstrap (RSFWB) to model the counterfactual outcomes while marginalizing over the auxiliary covariates. By maximizing the restricted mean survival time, we estimate the optimal regime for a target population based on a selected set of covariates. Simulation studies illustrate that the proposed method performs reliably across a range of different scenarios. We further apply RSFWB to a prostate cancer study.
个性化治疗策略需要根据每位患者的临床特征和其他特点来确定最佳治疗方案。在此,我们考虑实际中常见的一种情况,即在分析观察性队列数据时,存在一些辅助变量,它们既影响治疗又影响结果,但这些变量并非纳入可推广治疗策略时的主要关注对象。此外,对于治疗效果或协变量的重要性,我们没有足够的先验知识来明确指定结果与不同协变量之间的依赖关系,因此我们选择一个足够灵活的模型,以适应结果与协变量之间可能复杂的关联。我们考虑具有生存结局的观察性研究,并建议使用带加权自助法的随机生存森林(RSFWB)来对反事实结局进行建模,同时对辅助协变量进行边缘化处理。通过最大化受限平均生存时间,我们基于一组选定的协变量估计目标人群的最优治疗方案。模拟研究表明,所提出的方法在一系列不同场景下都能可靠地执行。我们进一步将RSFWB应用于一项前列腺癌研究。