Immortal time bias in pharmacoepidemiology
Immortal time bias in pharmacoepidemiology
复制标题
DOI：
10.1093/aje/kwm324
复制
发表时间：
2008-02-15
影响因子：
5
通讯作者：
Suissa, Samy
中科院分区：
文献类型：
--
作者：
Suissa, Samy
不朽时间是指队列随访的时间跨度，在此期间，由于暴露定义，研究中的结局无法发生。不死时间的偏倚最早是在20世纪70年代的流行病学中，在心脏移植生存获益的队列研究中发现的。它最近重新出现在药物流行病学中，几项观察性研究报告说，各种药物可以非常有效地降低发病率和死亡率。这些研究虽然使用了不同的队列设计，但都涉及某种形式的不朽时间和相应的偏倚。在本文中，作者描述了导致这种偏倚的各种队列研究设计，量化了不同生存分布下的偏倚大小，并通过使用肺癌患者队列的数据进行了说明。作者表明，对于基于时间、基于事件和基于确定性的队列定义，错误分类或排除不朽时间导致的率比偏倚与不朽时间的持续时间成比例增加。与指数分布的恒定风险相比，如Weibull分布所示，结局事件的风险函数越小，偏倚越明显。总之，使用计算机数据库的药物获益观察性研究必须进行适当的设计和分析，以避免永久性时间偏倚。
Immortal time is a span of cohort follow-up during which, because of exposure definition, the outcome under study could not occur. Bias from immortal time was first identified in the 1970s in epidemiology in the context of cohort studies of the survival benefit of heart transplantation. It recently resurfaced in pharmacoepidemiology, with several observational studies reporting that various medications can be extremely effective at reducing morbidity and mortality. These studies, while using different cohort designs, all involved some form of immortal time and the corresponding bias. In this paper, the author describes various cohort study designs leading to this bias, quantifies its magnitude under different survival distributions, and illustrates it by using data from a cohort of lung cancer patients. The author shows that for time-based, event-based, and exposure-based cohort definitions, the bias in the rate ratio resulting from misclassified or excluded immortal time increases proportionately to the duration of immortal time. The bias is more pronounced with a decreasing hazard function for the outcome event, as illustrated with the Weibull distribution compared with a constant hazard from the exponential distribution. In conclusion, observational studies of drug benefit in which computerized databases are used must be designed and analyzed properly to avoid immortal time bias.