Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
School of Social and Community Medicine, University of Bristol, Bristol, UK; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Ann Epidemiol. 2016 Sep;26(9):605-11. doi: 10.1016/j.annepidem.2016.07.009. Epub 2016 Aug 3.
PURPOSE: Observational studies are prone to (unmeasured) confounding. Sensitivity analysis of unmeasured confounding typically focuses on a single unmeasured confounder. The purpose of this study was to assess the impact of multiple (possibly weak) unmeasured confounders. METHODS: Simulation studies were performed based on parameters estimated from the British Women's Heart and Health Study, including 28 measured confounders and assuming no effect of ascorbic acid intake on mortality. In addition, 25, 50, or 100 unmeasured confounders were simulated, with various mutual correlations and correlations with measured confounders. RESULTS: The correlated unmeasured confounders did not need to be strongly associated with exposure and outcome to substantially bias the exposure-outcome association at interest, provided that there are sufficiently many unmeasured confounders. Correlations between unmeasured confounders, in addition to the strength of their relationship with exposure and outcome, are key drivers of the magnitude of unmeasured confounding and should be considered in sensitivity analyses. However, if the unmeasured confounders are correlated with measured confounders, the bias yielded by unmeasured confounders is partly removed through adjustment for the measured confounders. CONCLUSIONS: Discussions of the potential impact of unmeasured confounding in observational studies, and sensitivity analyses to examine this, should focus on the potential for the joint effect of multiple unmeasured confounders to bias results.
目的:观察性研究容易受到(未测量的)混杂因素的影响。未测量混杂因素的敏感性分析通常集中于单个未测量的混杂因素。本研究的目的是评估多个(可能较弱的)未测量混杂因素的影响。
方法:基于从英国女性心脏与健康研究中估计的参数进行模拟研究,包括 28 个已测量混杂因素,并假设维生素 C 摄入量对死亡率没有影响。此外,模拟了 25、50 或 100 个未测量混杂因素,它们之间存在各种相互关联和与已测量混杂因素的关联。
结果:相关的未测量混杂因素不需要与暴露和结局强烈相关,就可以实质性地偏倚感兴趣的暴露结局关联,前提是存在足够多的未测量混杂因素。未测量混杂因素之间的相关性,以及它们与暴露和结局的关系强度,是未测量混杂程度的关键驱动因素,应该在敏感性分析中加以考虑。然而,如果未测量混杂因素与已测量混杂因素相关,那么通过调整已测量混杂因素,可以部分消除未测量混杂因素产生的偏差。
结论:讨论观察性研究中未测量混杂的潜在影响,以及进行敏感性分析以检查这种影响,应重点关注多个未测量混杂因素的联合效应可能偏倚结果的情况。
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