title: Empirical evaluation of complex epidemiologic study designs: workplace exposure and cancer.
abstract: 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.
authors.affiliation: Brush Wellman, Inc, 14710 West Portage River South Road, Elmore, OH 43416, USA. david_deubner@brushwellman.com
authors.forename: David C
authors.initials: DC
authors.lastname: Deubner
authors.forename: H Daniel
authors.initials: HD
authors.lastname: Roth
authors.forename: Paul S
authors.initials: PS
authors.lastname: Levy
mesh_terms: D000328:Adult; D000367:Age Factors; D001608:Beryllium / Q000633:toxicity*; D015982:Bias; D016022:Case-Control Studies; D015331:Cohort Studies; D036262:Empirical Research; D015340:Epidemiologic Research Design; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000401:mortality*; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis* / Q000706:statistics & numerical data; D011897:Random Allocation; D012494:Sampling Studies; D013223:Statistics as Topic; D013997:Time Factors
chemical_list: D001608:Beryllium