Accommodating Measurements Below a Limit of Detection: A Novel Application of Cox Regression
Accommodating Measurements Below a Limit of Detection: A Novel Application of Cox Regression
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DOI：
10.1093/aje/kwu017
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发表时间：
2014-04-15
影响因子：
5
通讯作者：
Weinberg, Clarice R.
中科院分区：
文献类型：
--
作者：
Dinse, Gregg E.;Jusko, Todd A.;Weinberg, Clarice R.
在环境流行病学中，暴露生物标志物的测量常常低于检测的检测极限。现有的处理这个问题的方法，包括删除、替换、参数回归和多重补偿，如果未检测的比例很高或参数模型被错误指定，则性能很差。我们提出了一种方法，将测量的分析物视为模型化的结果，当分析物是健康结果的推定原因时，意味着角色颠倒。在比例反转之后，我们的方法使用COX回归对分析物进行建模，并进行混杂调整。该方法充分利用了可量化的分析物测量方法，同时适当地将未检测到的内容视为审查。在比例风险假设下，二元健康结果的风险比可解释为调整后的优势比：任何特定分析物浓度的结果的优势除以给定较低浓度的优势。我们的方法广泛适用于队列研究、病例对照研究(频率匹配与否)和为确定暴露的决定因素而进行的横断面研究。我们用横断面调查数据说明了这种方法，以评估性别作为2，3，7，8-四氯二苯并对二恶英浓度的决定因素，并使用前瞻性队列数据来评估2，4，4-三氯联苯暴露与精神运动发育之间的关联。
In environmental epidemiology, measurements of exposure biomarkers often fall below the assays limit of detection. Existing methods for handling this problem, including deletion, substitution, parametric regression, and multiple imputation, can perform poorly if the proportion of nondetects is high or parametric models are misspecified. We propose an approach that treats the measured analyte as the modeled outcome, implying a role reversal when the analyte is a putative cause of a health outcome. Following a scale reversal as well, our approach uses Cox regression to model the analyte, with confounder adjustment. The method makes full use of quantifiable analyte measures, while appropriately treating nondetects as censored. Under the proportional hazards assumption, the hazard ratio for a binary health outcome is interpretable as an adjusted odds ratio: the odds for the outcome at any particular analyte concentration divided by the odds given a lower concentration. Our approach is broadly applicable to cohort studies, case-control studies (frequency matched or not), and cross-sectional studies conducted to identify determinants of exposure. We illustrate the method with cross-sectional survey data to assess sex as a determinant of 2,3,7,8-tetrachlorodibenzo-p-dioxin concentration and with prospective cohort data to assess the association between 2,4,4-trichlorobiphenyl exposure and psychomotor development.