论文标题
双重稳定的估计器,用于概括从随机对照试验到目标人群的生存结果的治疗效果
Doubly robust estimators for generalizing treatment effects on survival outcomes from randomized controlled trials to a target population
论文作者
论文摘要
在随机对照试验(RCT)参与者与目标人群之间存在异质性的情况下,仅基于RCT评估治疗效果通常会导致对现实治疗效果的偏见。为了解决RCT样本估计的治疗效果缺乏普遍性的问题,我们利用代表目标人群的大量样本的观察性研究。本文涉及评估治疗对目标人群生存结果的影响,并考虑了一系列广泛的估计,这些估计值是特定治疗特定生存功能的功能,包括生存概率和限制平均生存时间的差异。由两种直观但不同的方法,即基于生存结果回归和加权基于采样,审查和治疗分配的加权的插补,我们建议通过指导有效的影响力功能,提出一个半参数估计器。如果生存模型或加权模型正确指定,则提出的估计器在目标群体估计的意义上是双重鲁棒的,并且当两者都正确时局部效率高。此外,作为参数估计的一种替代方法,我们采用了筛子的非参数方法来灵活和稳健地估计滋扰功能,并表明所得估计器保留了根-N的一致性和效率,即所谓的IT速率双重双重鲁棒性。仿真研究证实了所提出的估计量的理论特性,并表明其表现优于竞争者。我们应用了提出的方法来估计辅助化疗对早期切除的非小肺癌患者的生存作用。
In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment effect. To address the problem of lack of generalizability for the treatment effect estimated by the RCT sample, we leverage observational studies with large samples that are representative of the target population. This paper concerns evaluating treatment effects on survival outcomes for a target population and considers a broad class of estimands that are functionals of treatment-specific survival functions, including differences in survival probability and restricted mean survival times. Motivated by two intuitive but distinct approaches, i.e., imputation based on survival outcome regression and weighting based on inverse probability of sampling, censoring, and treatment assignment, we propose a semiparametric estimator through the guidance of the efficient influence function. The proposed estimator is doubly robust in the sense that it is consistent for the target population estimands if either the survival model or the weighting model is correctly specified, and is locally efficient when both are correct. In addition, as an alternative to parametric estimation, we employ the nonparametric method of sieves for flexible and robust estimation of the nuisance functions and show that the resulting estimator retains the root-n consistency and efficiency, the so-called it rate-double robustness. Simulation studies confirm the theoretical properties of the proposed estimator and show it outperforms competitors. We apply the proposed method to estimate the effect of adjuvant chemotherapy on survival in patients with early-stage resected non-small lung cancer.