Unanchored Population-Adjusted Indirect Comparison Methods for Time-to-Event Outcomes Using Inverse Odds Weighting, Regression Adjustment, and Doubly Robust Methods With Either Individual Patient or Aggregate Data.
Unanchored Population-Adjusted Indirect Comparison Methods for Time-to-Event Outcomes Using Inverse Odds Weighting, Regression Adjustment, and Doubly Robust Methods With Either Individual Patient or Aggregate Data.
复制标题
针对事件发生时间结果的非锚定群体调整间接比较方法，使用逆比值加权、回归调整和双稳健方法，针对个体患者或汇总数据。
DOI：
10.1016/j.jval.2023.11.011
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Park JE
中科院分区：
文献类型：
--
作者：
Park JE
几种方法无锚定人口调整的间接比较（PAIC）是可用的。根据外部研究中可用的个体患者数据（IPD）和汇总数据（AD），探索替代调整方法可能有助于最大限度地减少非锚定间接比较中的偏倚。然而，时间到事件结局的方法还没有得到很好的理解。本研究提供了一个概述和比较的方法，使用案例研究，以提高熟悉度。最近的一种方法被应用于边缘化条件风险比，这允许方法的比较，并提出了一个双重鲁棒的方法。MethodsThe以下PAIC方法通过三线小细胞肺癌的病例研究进行了比较，比较了纳武单抗与基于单臂II期试验的标准治疗（CheckMate 032）和真实世界研究（Flatiron）在总生存期方面：使用反向比值加权、回归调整和双重稳健方法的IPD-IPD分析;使用匹配调整的间接比较、模拟治疗比较进行的IPD-AD分析，结果与标准治疗相比，纳武利尤单抗延长了生存期，风险比范围为0.63（95% CI 0.44-0.90），在使用回归调整的IPD-IPD分析中为0.69（95% CI 0.44-0.98）。回归为基础的双重稳健估计产生了较宽的置信区间与倾向评分为基础的analysis.ConclusionsThe建议的双重稳健的方法，时间到事件的结果可能有助于尽量减少偏见，由于模型误设。然而，非锚定PAIC的所有方法都依赖于已纳入所有预后协变量的强假设。
ObjectivesSeveral methods for unanchored population-adjusted indirect comparisons (PAICs) are available. Exploring alternative adjustment methods, depending on the available individual patient data (IPD) and the aggregate data (AD) in the external study, may help minimize bias in unanchored indirect comparisons. However, methods for time-to-event outcomes are not well understood. This study provides an overview and comparison of methods using a case study to increase familiarity. A recent method is applied to marginalize conditional hazard ratios, which allows for the comparisons of methods, and a doubly robust method is proposed.MethodsThe following PAIC methods were compared through a case study in third-line small cell lung cancer, comparing nivolumab with standard of care based on a single-arm phase II trial (CheckMate 032) and real-world study (Flatiron) in terms of overall survival: IPD-IPD analyses using inverse odds weighting, regression adjustment, and a doubly robust method; IPD-AD analyses using matching-adjusted indirect comparison, simulated treatment comparison, and a doubly robust method.ResultsNivolumab extended survival versus standard of care with hazard ratios ranging from 0.63 (95% CI 0.44-0.90) in naive comparisons (identical estimates for IPD-IPD and IPD-AD analyses) to 0.69 (95% CI 0.44-0.98) in the IPD-IPD analyses using regression adjustment. Regression-based and doubly robust estimates yielded slightly wider confidence intervals versus the propensity score-based analyses.ConclusionsThe proposed doubly robust approach for time-to-event outcomes may help to minimize bias due to model misspecification. However, all methods for unanchored PAIC rely on the strong assumption that all prognostic covariates have been included.