Methodological issues regarding confounding and exposure misclassification in epidemiological studies of occupational exposures

Abstract

Confounding and exposure misclassification are issues that concern epidemiologists because of their potential to bias results of studies and complicate interpretations. In occupational epidemiology both are routinely raised to argue that an observed result is either a false positive or a false negative finding. Although it is important to consider the potential for limitations of epidemiologic investigations, judgment regarding their importance should be based on their actual likelihood of occurrence. This paper is based on our experience in epidemiologic analyses and a brief review of the literature regarding confounding and exposure misclassification. Examples of substantial confounding are rare in occupational epidemiology. In fact, even for studies of occupational exposures and lung cancer, tobacco-adjusted relative risks rarely differ appreciably from the unadjusted estimates. This is surprising because it seems the perfect situation for confounding to occur. Yet, despite the lack of evidence that confounding is a common problem, nearly every epidemiologic paper includes a lengthy discussion on uncontrolled or residual confounding. On the other hand, exposure misclassification probably occurs in all studies. The only question is, how much? The direction and magnitude of nondifferential exposure misclassification (the type most likely to occur in cohort studies) on estimates of relative risks can be largely predicted given knowledge on the degree of misclassification, that is, relatively small amounts of misclassification can bias relative risks substantially towards the null. The literature, however, is full of discussions implying that misclassification of exposure is an explanation for a positive finding. These comments are not to suggest that all potential limitations for epidemiologic studies should not be considered and evaluated. We do believe, however, that the likelihood of occurrence and the direction and magnitude of the effect should be more carefully and realistically considered when making judgments about study design or data interpretation.