药物流行病学中的不朽时间偏倚。

Immortal time bias in pharmaco-epidemiology.

作者信息

Suissa Samy

机构信息

Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada.

出版信息

Am J Epidemiol. 2008 Feb 15;167(4):492-9. doi: 10.1093/aje/kwm324. Epub 2007 Dec 3.

Abstract

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 pharmaco-epidemiology, 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.

摘要

不朽时间是队列随访的一段时间,在此期间,由于暴露定义,所研究的结局不可能发生。不朽时间偏差最早于20世纪70年代在流行病学中,在心脏移植生存获益的队列研究背景下被发现。它最近在药物流行病学中再次出现,有几项观察性研究报告称,各种药物在降低发病率和死亡率方面可能极其有效。这些研究虽然采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差。在本文中,作者描述了导致这种偏差的各种队列研究设计,量化了在不同生存分布下其大小,并通过一组肺癌患者的数据进行了说明。作者表明,对于基于时间、基于事件和基于暴露的队列定义,因错误分类或排除不朽时间而导致的率比偏差与不朽时间的持续时间成比例增加。结局事件的风险函数下降时,偏差更为明显,如威布尔分布所示,与指数分布的恒定风险相比。总之,使用计算机化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,以避免不朽时间偏差。

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