在竞争风险下精准评估治疗效果,助力个性化医疗决策
A Guide to Estimating Conditional Average Treatment Effects in Competing Risks Settings
- 用元学习框架整合生存模型与机器学习,估计患者特异性治疗效应
- 六种方法在多种场景下对比,发现随机生存森林+弹性网表现最优
- 提供R包crsurvlearners,适合医学研究者直接应用
条件平均治疗效应(CATE)是个性化医疗中制定治疗决策的核心。在竞争风险场景下,从生存数据中估计CATE可对特定事件的治疗效果进行患者级评估,同时合理考虑其他事件类型的影响。这一区分在合并症存在时尤为重要,否则其他死亡原因可能混淆治疗收益。本文聚焦右删失生存时间与二元治疗设定,定义CATE为固定时间点上事件相关绝对风险的协变量条件差异。我们系统研究了六种元学习器,结合Cox回归或随机生存森林用于风险建模,再搭配弹性网回归或随机森林进行直接CATE建模。通过多种模拟场景评估性能,涵盖危险函数复杂度、治疗异质性、治疗分配方式、事件类型分布及删失程度等变量。为便于实际应用,我们提供了R包crsurvlearners,实现所有方法。
原文摘要 · Abstract (English)
Conditional average treatment effects (CATEs) are central to treatment decision-making in personalized medicine. In competing risks settings, estimating CATEs from survival data allows for patient-specific assessments of treatment effectiveness for a specific event of interest while properly accounting for alternative event types. This distinction is essential in the presence of comorbidities, where competing causes of death may otherwise confound the therapeutic benefit. Focusing on right-censored survival times with binary treatment, we examine CATEs defined as covariate-conditional differences in the absolute risk for the event of interest at a fixed time. To this end, we study meta-learners which adapt machine learning algorithms for CATE estimation in competing risks scenarios. We systematically compare six meta-learners, combining Cox regression or random survival forests for risk modeling with elastic net regression or random forests for direct CATE modeling. To provide practical guidance on model selection, we evaluate their performance in multiple simulation settings, that differ in hazard complexity, treatment heterogeneity, treatment assignment, event type distribution and censoring. To facilitate applied use, we provide the R package, crsurvlearners, which implements all considered approaches.
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