Tweedie R L, Mengersen K L
Department of Statistics, Colorado State University, Fort Collins 80523, USA.
Stat Med. 1995;14(5-7):545-69. doi: 10.1002/sim.4780140514.
This paper outlines several meta-analytic approaches to the assessment of quantal dose-response relationships; that is, to the evaluation of an increase in the level of exposure to an agent and the associated relative risk of a disease when this is investigated over a number of different studies. Analysis is developed at two levels: first, a consistent method of evaluating the dose-response relationship is applied to each study, and second, an overall picture is obtained by comparing and combining these relationships. At the first stage, for an individual study, dose-response assessment involves choices of model and appropriate tests for trend, which are influenced by such issues as dose measurement and use of the unexposed group. At the second stage, different methods for pooling results across studies must be considered. These depend on the choices made in the first stage of analysis, with additional attention paid to heterogeneity, and possible bias due to studies included in meta-analysis. We describe these meta-analytic approaches for three methods of evaluating dose response. The approaches are illustrated by evaluating the relationship between lung cancer and levels of exposure to environmental tobacco smoke (ETS). The strength of this relationship has been a point of debate in recent assessment of evidence for an overall carcinogenic effect of ETS exposure. We find little indication of a consistent dose response, a result explained in terms of recent models for cancer and passive smoking developed by Darby and Pike, the current meta-analysis results of overall risk-ratios of current studies in Tweedie and Mengersen, and misclassification models developed by the United States Environmental Protection Agency (EPA).
本文概述了几种用于评估定量剂量反应关系的荟萃分析方法；即，当在多项不同研究中对某种因素的暴露水平增加及其相关疾病相对风险进行研究时，对其进行评估。分析在两个层面展开：首先，将一种评估剂量反应关系的一致方法应用于每项研究；其次，通过比较和综合这些关系得出总体情况。在第一阶段，对于单个研究，剂量反应评估涉及模型选择和趋势的适当检验，这些会受到剂量测量和未暴露组使用等问题的影响。在第二阶段，必须考虑跨研究汇总结果的不同方法。这些方法取决于在分析第一阶段所做的选择，同时要额外关注异质性以及荟萃分析中纳入的研究可能存在的偏差。我们针对三种评估剂量反应的方法描述了这些荟萃分析方法。通过评估肺癌与环境烟草烟雾（ETS）暴露水平之间的关系来说明这些方法。在近期对ETS暴露总体致癌效应证据的评估中，这种关系的强度一直是一个争论点。我们几乎没有发现一致剂量反应的迹象，这一结果可根据达比和派克最近提出的癌症与被动吸烟模型、特威迪和门格森当前研究中总体风险比的荟萃分析结果以及美国环境保护局（EPA）开发的错误分类模型来解释。
