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The case-control study is the design most widely used in etiologic research. In contrast to cohort studies, in which subjects are assembled based on exposure characteristics, subject selection in a case-control study is based on disease status. Individuals who have already developed the disease become eligible for recruitment as cases, and a sample of those who are disease-free are selected as controls. Following selection, all subjects are assessed for a history of the occurrence of exposures (or events) of interest prior to disease onset. This is generally achieved through extensive personal interviews or self-administered questionnaires. Since the design stipulates that the investigator select subjects who already have the disease, case-control studies are especially well suited for rare diseases(for which it would take many years to follow a large number of unaffected subjects to determine whether disease occurs). Case-control studies have many other advantages in the study of the etiology of multiple sclerosis (MS)(table 1), including the ability to investigate a large number of risk factors in the same study, and the relative ease of recruiting a sufficient number of subjects at one time. The fact that the disease and the exposure to risk factors have already occurred at the time of the case-control study, however, means that case-control studies are especially are especially subject to a variety of types of bias that can threaten the validity of the results.
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Table 1 Advantages and disadvantages of case-control studies
The three main forms of bias are selection bias, measurement bias, and confounding bias.1 Selection bias can occur, for example, when the cases are recruited into the study such that they are more likely to have been exposed (that is, have a higher prevalence of exposure) to risk factors than the population of cases theoretically available for study. Such a bias …
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