Differential exposure misclassification in case-control studies of environmental tobacco smoke and lung cancer

We review some of the literature on the effects of exposure misclassification on the statistical analysis of case-control studies. In particular, we focus on evidence for exposure misclassification which may be different for cases and controls in studies of environmental tobacco smoke (ETS). For example, such misclassification could induce relative risk estimates below unity for low exposure which appears to be the case in U.S. lung cancer and ETS studies. We describe procedures for systematically examining the sensitivity of dose-response statistics on exposure misclassification. The procedures demonstrate how p-values for the null hypothesis of no dose-response trend could be adjusted to account for exposure misclassification. The adjustment procedures were applied to an example based on a recently published large study of ETS and lung cancer in which a p-value for trend was reported as 0.03. In this example it is seen that modest differential exposure misclassification can induce substantial increases in the actual p-value, changing what appears to be statistically significant to decidedly nonsignificant.