METAANALYTIC APPROACHES TO DOSE-RESPONSE RELATIONSHIPS, WITH APPLICATION IN STUDIES OF LUNG-CANCER AND EXPOSURE TO ENVIRONMENTAL TOBACCO-SMOKE

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 r elative risk of a disease when this is investigated over a number of d ifferent studies. Analysis is developed at two levels: first, a consis tent method of evaluating the dose-response relationship is applied to each study, and second, an overall picture is obtained by comparing a nd combining these relationships. At the first stage, for an individua l study, dose-response assessment involves choices of model and approp riate tests for trend, which are influenced by such issues as dose mea surement and use of the unexposed group, At the second stage, differen t methods for pooling results across studies must be considered. These depend on the choices made in the first stage of analysis, with addit ional attention paid to heterogeneity, and possible bias due to studie s included in meta-analysis. We describe these meta-analytic approache s for three methods of evaluating dose response. The approaches are il lustrated by evaluating the relationship between lung cancer and level s of exposure to environmental tobacco smoke (ETS). The strength of th is relationship has been a point of debate in recent assessment of evi dence for an overall carcinogenic effect of ETS exposure. We find litt le indication of a consistent dose response, a result explained in ter ms 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 Tweedle and Mengersen, and misclassification models developed by the United States Environmental Protection Agency (EPA).