Yang Guoyi, Burgess Stephen, Schooling Catherine Mary
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Int J Epidemiol. 2024 Dec 16;54(1). doi: 10.1093/ije/dyae176.
Immortal time is a period of follow-up during which death or the study outcome cannot occur by design. Bias from immortal time has been increasingly recognized in epidemiological studies. However, the fundamental causes and structures of bias from immortal time have not been explained systematically.
We use an example 'Does winning a Nobel Prize prolong lifespan?' for illustration. We illustrate how immortal time arises and present structures of bias from immortal time using directed acyclic graphs that specify time-varying variables. We further explore the structures of bias with the exclusion of immortal time and with the presence of competing risks. We discuss how these structures are shared by different study designs in pharmacoepidemiology and provide solutions, where possible, to address the bias.
The fundamental cause of immortal time is misalignment of exposure allocation and eligibility. Specifically, immortal time arises from using post-eligibility information to define exposure or using post-exposure information to define eligibility. The structures of bias from immortal time are confounding by survival until exposure allocation or selection bias from selecting on survival until eligibility. Excluding immortal time from follow-up does not fully address this confounding or selection bias, and the presence of competing risks can worsen the bias. Bias from immortal time may be avoided by aligning baseline, exposure allocation and eligibility, and by excluding individuals with prior exposure.
Understanding bias from immortal time in terms of confounding or selection bias helps researchers identify and thereby avoid or ameliorate this bias.
不朽时间是一段随访期，在此期间，根据设计，死亡或研究结果不会发生。不朽时间导致的偏倚在流行病学研究中日益受到关注。然而，不朽时间导致偏倚的根本原因和结构尚未得到系统解释。
我们用一个例子“获得诺贝尔奖会延长寿命吗？”来说明。我们通过有向无环图展示不朽时间是如何产生的，并呈现不朽时间导致的偏倚结构，该图指定了随时间变化的变量。我们进一步探讨排除不朽时间和存在竞争风险时的偏倚结构。我们讨论这些结构在药物流行病学的不同研究设计中是如何共有的，并在可能的情况下提供解决偏倚的方法。
不朽时间的根本原因是暴露分配与合格标准不一致。具体而言，不朽时间源于使用合格后信息来定义暴露，或使用暴露后信息来定义合格标准。不朽时间导致的偏倚结构是在暴露分配前的生存混杂，或在合格前的生存选择偏倚。从随访中排除不朽时间并不能完全解决这种混杂或选择偏倚，竞争风险的存在会使偏倚加剧。通过使基线、暴露分配和合格标准一致，并排除有既往暴露的个体，可以避免不朽时间导致的偏倚。
从混杂或选择偏倚的角度理解不朽时间导致的偏倚，有助于研究人员识别并因此避免或减轻这种偏倚。
