Empirical evaluation of complex epidemiologic study designs: workplace exposure and cancer

To test whether a frequently used cohort-nested case-control study design exaggerated exposure-response relationships because of unrecognized study design bias. Our aim was to evaluate empirically the performance of this complex study design.

We applied the design from one such study to a closely related cohort using randomly selected probands as cases. Values for average exposures were assigned to probands equal to, greater than, and less than those assigned to controls (matches).

Under certain lag scenarios, the nested study design produced higher average exposure in probands compared with their matches, even when this was clearly not the case.

Empirical evaluation demonstrated that the study design produced a biased case-control lagged exposure difference under the null hypothesis and could not distinguish qualitatively between null and alternate hypotheses. Empirical evaluation provided a useful check on results generated from a complex study design. It gave useful insight into the behavior of the index study design that was not otherwise readily deducible.