RTI Health Solutions, Research Triangle Institute, Research Triangle Park, NC 27709, USA.
Ann Epidemiol. 2011 Oct;21(10):773-9. doi: 10.1016/j.annepidem.2011.03.008. Epub 2011 Apr 16.
Beryllium is classified as carcinogenic on the basis largely of limited human data showing a modest increase in lung cancer from occupational exposure. With occupational exposure now curtailed, earlier results merit more scrutiny. We simulated data to understand the design implications of a landmark case-control study.
We generated datasets from the original occupational cohort by randomly assigning lung cancer events to workers independently of their exposure. We analyzed the simulated data on the basis of different modes of risk-set sampling, with risk sets defined by calendar time, age, or both, to assess how much bias existed using several exposure metrics. We controlled for several time related variables to assess confounding. Finally, we re-analyzed the data from the original study, controlling for time-related covariates.
No bias occurred using any type of risk-set sampling with unlagged exposures. When exposure was lagged 10 or 20 years, however, there was considerable confounding by year of birth and year of hire, which remained uncontrolled in the original study.
Simulations and reanalysis show that much of the reported association with lagged exposure is attributable to confounding by year of birth and year of hire. Lagging changes the exposure variable and can thus lead to changes in the amount of confounding.
铍被归类为致癌物质，主要基于有限的人类数据显示，职业暴露会导致肺癌发病率略有增加。由于职业暴露现在已得到控制，早期的结果值得更仔细的审查。我们模拟数据，以了解一项具有里程碑意义的病例对照研究的设计意义。
我们通过随机将肺癌事件分配给工人，而与他们的暴露无关，从原始职业队列中生成数据集。我们根据不同的风险集抽样模式（按日历时间、年龄或两者同时定义风险集）分析模拟数据，以评估使用几种暴露指标存在多少偏差。我们控制了几个与时间相关的变量以评估混杂因素。最后，我们控制了与时间相关的协变量，重新分析了原始研究的数据。
使用无滞后暴露的任何类型的风险集抽样都没有出现偏差。然而，当暴露滞后 10 或 20 年时，出生年份和入职年份的混杂因素很大，而在原始研究中未得到控制。
模拟和重新分析表明，报告的与滞后暴露相关的大部分关联归因于出生年份和入职年份的混杂因素。滞后改变了暴露变量，因此可能导致混杂因素的变化。
