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

J Occup Environ Med. 2007 Sep;49(9):953-9. doi: 10.1097/JOM.0b013e318145b28d.


Objective: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Beryllium / toxicity*
  • Bias
  • Case-Control Studies
  • Cohort Studies
  • Empirical Research
  • Epidemiologic Research Design*
  • Humans
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / mortality*
  • Middle Aged
  • Occupational Exposure / analysis*
  • Occupational Exposure / statistics & numerical data
  • Random Allocation
  • Sampling Studies
  • Statistics as Topic
  • Time Factors


  • Beryllium