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职业流行病学中剂量反应分析与风险评估实用指南。

A practical guide to dose-response analyses and risk assessment in occupational epidemiology.

作者信息

Steenland Kyle, Deddens James A

机构信息

Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA.

出版信息

Epidemiology. 2004 Jan;15(1):63-70. doi: 10.1097/01.ede.0000100287.45004.e7.

Abstract

Dose-response modeling in occupational epidemiology is usually motivated by questions of causal inference (eg, is there a monotonic increase of risk with increasing exposure?) or risk assessment (eg, how much excess risk exists at any given level of exposure?). We focus on several approaches to dose-response in occupational cohort studies. Categorical analyses are useful for detecting the shape of dose-response. However, they depend on the number and location of cutpoints and result in step functions rather than smooth curves. Restricted cubic splines and penalized splines are useful parametric techniques that provide smooth curves. Although splines can complement categorical analyses, they do not provide interpretable parameters. The shapes of these curves will depend on the degree of "smoothing" chosen by the analyst. We recommend combining categorical analyses and some type of smoother, with the goal of developing a reasonably simple parametric model. A simple parametric model should serve as the goal of dose-response analyses because (1) most "true" exposure response curves in nature may be reasonably simple, (2) a simple parametric model is easily communicated and used by others, and (3) a simple parametric model is the best tool for risk assessors and regulators seeking to estimate individual excess risks per unit of exposure. We discuss these issues and others, including whether the best model is always the one that fits the best, reasons to prefer a linear model for risk in the low-exposure region when conducting risk assessment, and common methods of calculating excess lifetime risk at a given exposure from epidemiologic results (eg, from rate ratios). Points are illustrated using data from a study of dioxin and cancer.

摘要

职业流行病学中的剂量反应建模通常是由因果推断问题(例如,风险是否随着暴露增加而单调增加?)或风险评估问题(例如,在任何给定暴露水平下存在多少额外风险?)所推动的。我们关注职业队列研究中几种剂量反应的方法。分类分析对于检测剂量反应的形状很有用。然而,它们取决于切点的数量和位置,并产生阶梯函数而非平滑曲线。受限立方样条和惩罚样条是有用的参数技术,可提供平滑曲线。尽管样条可以补充分类分析,但它们不能提供可解释的参数。这些曲线的形状将取决于分析师选择的“平滑”程度。我们建议将分类分析与某种类型的平滑方法相结合,目标是开发一个相当简单的参数模型。一个简单的参数模型应该作为剂量反应分析的目标,因为(1)自然界中大多数“真实”的暴露反应曲线可能相当简单,(2)一个简单的参数模型易于被他人交流和使用,(3)一个简单的参数模型是风险评估者和监管者寻求估计每单位暴露的个体额外风险的最佳工具。我们讨论这些问题以及其他问题,包括最佳模型是否总是拟合最好的那个,在进行风险评估时在低暴露区域倾向于使用线性风险模型的原因,以及根据流行病学结果(例如,从率比)计算给定暴露下超额终身风险的常用方法。使用二恶英与癌症研究的数据来说明这些要点。

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