The "case-control" study: valid selection of subjects.

For valid selection of subjects in "case-control" (case-referent) studies it is critical to understand that these studies do not represent an alternative to cohort studies but, rather, to census-ascertainment of the facts about the study base. Specifically, in these studies, the fact-finding scheme is to obtain a census of the study base with respect to outcome, and then a census of the cases together with a sample of the base to gather information on the determinant(s) as well as modifiers and confounders. If the base is defined a priori (primary base), then the challenge is to devise a scheme to obtain a census of the cases in it and a sample of the base itself ("control" or reference series) that is representative of it, conditional on the covariates that will be controlled in the analysis of the data. On the other hand, if the definition of the base is secondary, a corollary of the way the cases are selected, then the case series is best viewed as the totality of the cases in the base as a matter of definition. The corresponding secondary base is the population experience in which each potential case, had it occurred, would have been included in the case series. Representative sampling of a secondary base tends to call for the use of subjects coming to the source of cases because of other conditions--conditions whose occurrence is known to be unrelated to the determinant under study and whose diagnosis and referral to the source are known to have the same relation to the determinant as those of the illness under study. With both types of base, primary and secondary, the accuracy of the information on the determinant should be comparable between the case and reference series, and this requirement of comparability, just as that of representativeness, can have important implications for the selection of the study subjects.