Sources of uncertainty in dose-response modeling of epidemiological data for cancer risk assessment.
Stayner-L; Bailer-AJ; Smith-R; Gilbert-S; Rice-F; Kuempel-E
Ann NY Acad Sci 1999 Dec; 895(1):212-222
Epidemiologic data is increasingly being used for dose-response analysis in risk assessment. The Environmental Protection Agency (EPA) and other U.S. agencies have expressed a preference for using epidemiologic data rather than toxicologic data when possible. However, there are a number of important sources of uncertainty in using epidemiologic data for this purpose that need to be clearly recognized and, when possible, quantified. This paper presents a critical review of the major sources of uncertainty in the use of epidemiologic data for cancer risk assessment. These may include: (1) study design issues such as potential confounding and other biases, inadequate sample size, and followup, (2) the choice of the data set, (3) specification of the dose-response model, (4) estimation of exposure and dose, and (5) unrecognized variability in susceptibility. Examples from risk assessments for cadmium, asbestos, and diesel exhaust are used to illustrate the potential magnitude of some of these sources of uncertainty. It is shown that the overall uncertainty from these various sources combined may often result in highly uncertain risk estimates from dose-response modeling of epidemiologic data. For this reason, we believe it is best to present a range of possible risk estimates, which, to the extent possible, reflects the variability and uncertainty inherent in the dose-response evaluation of epidemiologic data.
Risk-analysis; Risk-factors; Statistical-analysis; Analytical-processes; Analytical-methods; Exposure-assessment; Quantitative-analysis; Dose-response; Biomarkers; Epidemiology; Cancer-rates; Cancer; Cadmium-compounds; Cadmium-dust; Asbestos-dust; Asbestos-fibers; Diesel-exhausts
National Institute for Occupational Safety and Health, Education and Information Division, Risk Evaluation Branch, 4676 Columbia Parkway, Cincinnati, Ohio 45226, USA
Annals of the New York Academy of Sciences