The case-referent study--some comments on its structure, merits and limitations.

Case-referent (case-control) studies have become increasingly important in occupational health epidemiology. The concept of study base [Miettinen, Scand J Work Environ Health 8 (1982):suppl 1, 7-14] as referring to the health experience of the study population over time, and a clear recognition of open and closed populations, ie, with or without turnover, make the structure of the case-referent study clearer. The referents should represent the study base in terms of exposure and nonexposure and even with regard to other determinants of the disease under study. Case-referent studies refer to open populations unless nested in cohorts. Matching in cohort studies is straight-forward and creates a symmetrical situation among the exposed and unexposed with regard to the matching factor, but this symmetry is not achieved in case-referent studies, in which matching tends to distort the representativeness of the referents with regard to the study base. This circumstance suggests that matching on determinants of the disease should be maintained in the analysis. However, since the referents are a sample of the base, there might be confounding in the data, which does not exist in the base and vice versa, ie, full control of confounding in case-referent studies is not achievable either through matching or through any other procedure, but a large sample of referents would more properly reflect the distribution of confounders in the base. Using hospital referents, one has to consider possible relations between the referent diseases and the exposure under study, and therefore evaluation of multiple exposures may even require different sets of hospital referents.(ABSTRACT TRUNCATED AT 250 WORDS)