Methodologic Issues in Using Epidemiologic Studies for Quantitative Risk Assessment

Although animal studies have been used most often for quantitative risk assessment, it is generally recognized that well-conducted epidemiologic studies would provide the best basis for estimating human risk. However, there are several features related to the design and analysis of epidemiologic studies that frequently limit their usefulness for quantitating risks. The lack of accurate information on exposure in epidemiologic studies is perhaps the most frequently cited limitation of these studies for risk assessment. However. other features of epidemiologic study design, such as statistical power, length of follow-up, confounding, and effect modification, may also limit the inferences that can be drawn from these studies. Furthermore, even when the aforementioned limitations are overcome, substantial uncertainty exists concerning the choice of an appropriate statistical (or biologic) model for extrapolation beyond the range of exposures observed in a particular study. This paper focuses on presenting a review and discussion of the methodologic issues involved in using epidemiologic studies for risk assessment. This review concentrates on the use of retrospective, cohort, mortality studies of occupational groups for assessing cancer risk because this is the most common application of epidemiologic data for quantitative risk assessment (QRA). Epidemiologic data should not be viewed as a panacea for the problems inherent in using animal bioassay data for QRA. Rather, information that can be derived from epidemiologic and toxicologic studies complement one another, and both data sources need to be used to provide the best characterization of human risk.