Assessing dose-response relationships by cumulative exposures in epidemiological studies

Background If the occurrence of disease monotonically increases with the degree of exposure in an epidemiologic study, a dose-response (or exposure-response) relationship is indicated and facilitates the interpretation that the exposure has a causal role. It is not uncommon, however, that there is some effect in terms of an overall increased relative risk but no clear dose-response relationship. Methods Models presented here show that cumulative exposure, as involving the duration of exposure, is not an adequate parameter when more recent exposure or the intensity of the exposure plays the greater role for the disease outcome. Conclusions In lack of a dose-response pattern by cumulative exposure, the interpretation of an overall increased risk might well be that there is no definite effect. The proper consideration should be, however that the measure of exposure could be inadequate, suggesting a need for further analyses and evaluations of the material studied. (c) 2007 Wiley-Liss, Inc.