Due to the heterogeneity of the randomized controlled trial (RCT) and external target populations, the estimated treatment effect from the RCT is not directly applicable to the target population. For example, the patient characteristics of the ACTG 175 HIV trial are significantly different from that of the three external target populations of interest: US early-stage HIV patients, Thailand HIV patients, and southern Ethiopia HIV patients. This paper considers several methods to transport the treatment effect from the ACTG 175 HIV trial to the target populations beyond the trial population. Most transport methods focus on continuous and binary outcomes; on the contrary, we derive and discuss several transport methods for survival outcomes: an outcome regression method based on a Cox proportional hazard (PH) model, an inverse probability weighting method based on the models for treatment assignment, sampling score, and censoring, and a doubly robust method that combines both methods, called the augmented calibration weighting (ACW) method. However, as the PH assumption was found to be incorrect for the ACTG 175 trial, the methods that depend on the PH assumption may lead to the biased quantification of the treatment effect. To account for the violation of the PH assumption, we extend the ACW method with the linear spline-based hazard regression model that does not require the PH assumption. Applying the aforementioned methods for transportability, we explore the effect of PH assumption, or the violation thereof, on transporting the survival results from the ACTG 175 trial to various external populations.
翻译:由于随机控制试验(RCT)和外部目标人群的异质性,RCT的估计治疗效应并不直接适用于目标人群,例如,ACT175艾滋病毒试验的病人特征与三个感兴趣的外部目标人群(美国早期艾滋病毒病人、泰国艾滋病毒病人和埃塞俄比亚南部艾滋病毒病人)的病人特征大不相同。本文考虑了将ACT175艾滋病毒试验的治疗效应从ACT175艾滋病毒试验转移到试验人群以外的目标人群的若干方法。大多数运输方法侧重于连续和二进制结果;相反,我们得出和讨论几种生存结果的运输方法:基于Cox比例危害(PH)模型的结果回归方法,基于治疗分配、抽样评分和检查模式的逆差概率加权方法,以及结合这两种方法的双倍稳健方法,要求加强校准权重(ACW)方法。然而,由于发现PH假设在ACTG175各种试验中并不正确,因此取决于PH假设可能导致对治疗效果的偏差量化。根据CH标准计算结果的结果,根据CH原则,我们根据Cox比例假设的BRA值假设,我们适用了PHRB的运输结果。