A practical guide to dose-response analyses and risk assessment in occupational epidemiology

Dose-response modeling in occupational epidemiology is usually motivated by questions of causal inference (eg, is there a monotonic increase of risk with increasing exposure?) or risk assessment (eg, how much excess risk exists at any given level of exposure?). We focus on several approaches to dose-response in occupational cohort studies. Categorical analyses are useful for detecting the shape of dose-response. However, they depend on the number and location of cutpoints and result in step functions rather than smooth curves. Restricted cubic splines and penalized splines are useful parametric techniques that provide smooth curves. Although splines can complement categorical analyses, they do not provide interpretable parameters. The shapes of these curves will depend on the degree of smoothing chosen by the analyst. We recommend combining categorical analyses and some type of smoother, with the goal of developing a reasonably simple parametric model. A simple parametric model should serve as the goal of dose-response analyses because (1) most true exposure response curves in nature may be reasonably simple, (2) a simple parametric model is easily communicated and used by others, and (3) a simple parametric model is the best tool for risk assessors and regulators seeking to estimate individual excess risks per unit of exposure. We discuss these issues and others, including whether the best model is always the one that fits the best, reasons to prefer a linear model for risk in the low-exposure region when conducting risk assessment, and common methods of calculating excess lifetime risk at a given exposure from epidemiologic results (eg, from rate ratios). Points are illustrated using data from a study of dioxin and cancer.