MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Int J Epidemiol. 2018 Apr 1;47(2):587-596. doi: 10.1093/ije/dyx213.
Negative control exposure studies are increasingly being used in epidemiological studies to strengthen causal inference regarding an exposure-outcome association when unobserved confounding is thought to be present. Negative control exposure studies contrast the magnitude of association of the negative control, which has no causal effect on the outcome but is associated with the unmeasured confounders in the same way as the exposure, with the magnitude of the association of the exposure with the outcome. A markedly larger effect of the exposure on the outcome than the negative control on the outcome strengthens inference that the exposure has a causal effect on the outcome.
We investigate the effect of measurement error in the exposure and negative control variables on the results obtained from a negative control exposure study. We do this in models with continuous and binary exposure and negative control variables using analysis of the bias of the estimated coefficients and Monte Carlo simulations.
Our results show that measurement error in either the exposure or negative control variables can bias the estimated results from the negative control exposure study.
Measurement error is common in the variables used in epidemiological studies; these results show that negative control exposure studies cannot be used to precisely determine the size of the effect of the exposure variable, or adequately adjust for unobserved confounding; however, they can be used as part of a body of evidence to aid inference as to whether a causal effect of the exposure on the outcome is present.
当认为存在未观察到的混杂因素时，阴性对照暴露研究越来越多地被用于流行病学研究中，以加强暴露-结局关联的因果推断。阴性对照暴露研究对比了阴性对照的关联程度，阴性对照对结局没有因果影响，但与未测量的混杂因素的关联方式与暴露相同，与暴露与结局的关联程度进行对比。暴露对结局的影响明显大于阴性对照对结局的影响，这加强了暴露对结局有因果影响的推断。
我们研究了暴露和阴性对照变量中的测量误差对阴性对照暴露研究结果的影响。我们在连续和二分类暴露和阴性对照变量的模型中，使用估计系数的偏差分析和蒙特卡罗模拟来进行研究。
我们的结果表明，暴露或阴性对照变量中的测量误差都可能会对阴性对照暴露研究的估计结果产生偏差。
在流行病学研究中使用的变量中，测量误差很常见；这些结果表明，阴性对照暴露研究不能用来精确确定暴露变量的效应大小，或充分调整未观察到的混杂因素；然而，它们可以作为证据的一部分，帮助推断暴露对结局是否存在因果效应。
