Use of the landmark method to address immortal person-time bias in comparative effectiveness research: a simulation study
Use of the landmark method to address immortal person-time bias in comparative effectiveness research: a simulation study
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DOI：
10.1002/sim.7019
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发表时间：
2016-10-01
影响因子：
2
通讯作者：
Setoguchi, Soko
中科院分区：
文献类型：
--
作者：
Mi, Xiaojuan;Hammill, Bradley G.;Setoguchi, Soko
观察性比较有效性和安全性研究通常需要不朽的人时间，即一段随访时间，在此期间由于治疗定义而无法出现结果。众所周知，常见的方法（例如从分析中排除不朽时间或天真地将不朽时间纳入分析）会导致对治疗效果的估计出现偏差。其他方法，例如曼特尔-拜亚尔法和地标法，也被提出来处理不朽时间。关于地标方法在不同场景下的性能知之甚少。我们进行了广泛的蒙特卡罗模拟，以评估地标方法与反映现实场景的设置中的其他方法相比的性能。我们考虑了界标方法的四个界标时间。我们发现，Mantel-Byar 方法在所有情况下都提供了无偏估计，而当事件的危险恒定或随着时间的推移而减少时，排除方法和朴素方法会导致很大的偏差。当治疗效果较小时，里程碑方法在纠正所有场景中的不朽人时偏差方面表现良好，并且在没有治疗效果时提供无偏估计。当早期随访期间的治疗率高于后期治疗率时，与标志性方法相关的偏倚往往较小。这些发现在慢性阻塞性肺病的案例研究中得到了证实。版权所有 (C) 2016 约翰·威利父子有限公司
Observational comparative effectiveness and safety studies are often subject to immortal person-time, a period of follow-up during which outcomes cannot occur because of the treatment definition. Common approaches, like excluding immortal time from the analysis or naively including immortal time in the analysis, are known to result in biased estimates of treatment effect. Other approaches, such as the Mantel-Byar and landmark methods, have been proposed to handle immortal time. Little is known about the performance of the landmark method in different scenarios. We conducted extensive Monte Carlo simulations to assess the performance of the landmark method compared with other methods in settings that reflect realistic scenarios. We considered four landmark times for the landmark method. We found that the Mantel-Byar method provided unbiased estimates in all scenarios, whereas the exclusion and naive methods resulted in substantial bias when the hazard of the event was constant or decreased over time. The landmark method performed well in correcting immortal person-time bias in all scenarios when the treatment effect was small, and provided unbiased estimates when there was no treatment effect. The bias associated with the landmark method tended to be small when the treatment rate was higher in the early follow-up period than it was later. These findings were confirmed in a case study of chronic obstructive pulmonary disease. Copyright (C) 2016 John Wiley & Sons, Ltd.