论文标题
将HIV临床试验的生存运送到外部目标人群
Transporting survival of an HIV clinical trial to the external target populations
论文作者
论文摘要
由于随机对照试验（RCT）和外部目标种群的异质性，RCT的估计治疗效果不适用于目标群体。例如，ACTG 175 HIV试验的患者特征与感兴趣的三个外部目标种群中的患者特征显着不同：美国早期HIV患者，泰国HIV患者和埃塞俄比亚南部HIV患者。本文考虑了几种将治疗效果从ACTG 175 HIV试验转移到试验人群以外的目标人群的方法。大多数运输方法都集中在连续和二进制的结果上；相反，我们得出并讨论了几种生存结果的传输方法：基于COX比例危害（PH）模型的结果回归方法，一种基于治疗分配的模型，采样得分和审查的模型，一种双重鲁棒的方法，一种结合了这两种方法，称为增强的校准权重（ACW）方法。但是，由于发现ACTG 175试验的pH假设是不正确的，因此取决于pH假设的方法可能导致治疗效果的偏见定量。为了说明违反pH假设的行为，我们使用基于线性样条的危害回归模型扩展了ACW方法，该模型不需要pH假设。应用上述方法以进行可运输能力，我们探讨了pH假设或违规行为对运输ACTG 175试验的生存结果的影响。
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.
