Assessing, accommodating, and interpreting the influences of heterogeneity

Heterogeneity, ranging from measurement error to variation among individuals or regions, influences all levels of data collected for risk assessment. In its role as a nemesis, heterogeneity can reduce the precision of estimates, change the shape of a population model, or reduce the generalizability of study results. In many contexts, however, heterogeneity is the primary object of inference. Indeed, some degree of heterogeneity in excess of a baseline amount associated with a statistical model is necessary in order to identify important determinants of response. This report outlines the causes and influences of heterogeneity, develops statistical methods used to estimate and account for it, discusses interpretations of heterogeneity, and shows how it should influence study design. Examples from dose-response modeling, identification of sensitive individuals, assessment of small area variations and meta analysis provide applied contexts.