Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies
Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies
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DOI：
10.1093/aje/kwv445
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发表时间：
2016-08-15
影响因子：
5
通讯作者：
Tremlett, Helen
中科院分区：
文献类型：
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作者：
Karim, Mohammad Ehsanul;Gustafson, Paul;Tremlett, Helen
在药物有效性观察性研究的至事件发生时间分析中，对队列入组和随访期间首次治疗暴露之间的时间段处理不当可能导致永久性时间偏倚。通过时间依赖性分析（如拟合时间依赖性考克斯模型）确认治疗暴露状态的变化，可消除该偏倚。处方时间分布匹配（PTDM）方法已被提出作为一种简单的方法来控制不朽的时间偏差。使用模拟研究和理论量化的偏差，我们比较了PTDM方法的性能与时间依赖的考克斯模型中存在不朽的时间。两项评估均显示PTDM方法未充分解决永生时间偏倚。基于我们的模拟结果，另一个最近提出的观测数据分析技术，序贯考克斯方法，被发现是更有用的比PTDM方法（考克斯：偏差=-0.002，均方误差= 0.025; PTDM：偏差=-1.411，均方误差= 2.011）。我们应用这些方法研究β-干扰素治疗与延迟加拿大不列颠哥伦比亚省多发性硬化症队列残疾进展的相关性（β-干扰素治疗多发性硬化症的长期获益和不良反应（BeAMS）研究，1995-2008）。
In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time. Both assessments revealed that the PTDM approach did not adequately address immortal time bias. Based on our simulation results, another recently proposed observational data analysis technique, the sequential Cox approach, was found to be more useful than the PTDM approach (Cox: bias = -0.002, mean squared error = 0.025; PTDM: bias = -1.411, mean squared error = 2.011). We applied these approaches to investigate the association of beta-interferon treatment with delaying disability progression in a multiple sclerosis cohort in British Columbia, Canada (Long-Term Benefits and Adverse Effects of Beta-Interferon for Multiple Sclerosis (BeAMS) Study, 1995-2008).