Case–Control Studies

In a cohort study, the numerator and denominator of each disease frequency (incidence proportion, incidence rate, or incidence odds) are measured, which requires enumerating the entire population and keeping it under surveillance. A case-control study observes the population more efficiently by using a sample of the population, which becomes the control series, in place of complete assessment of the denominators of the disease frequencies. This extra sampling step can make a case-control study much more efficient than a cohort study of the same population, but it introduces a number of subtleties and avenues for bias that are absent in typical cohort studies. For diseases that are sufficiently rare, cohort studies become impractical, and case-control studies become the only useful alternative. The cases in a case-control study should be the same people who would be considered cases in a cohort study of the same population. The definition of the source population for these cases determines the population from which controls should be sampled. Ideally, control selection would involve direct sampling from the source population, with equal probability of selection, although in many circumstances, variations in and substitutes for this ideal sampling design may be considered. Keywords: case-cohort study; case-crossover study; case-specular study; cohort study; density sampling; epidemiology; nested case-control study; odds ratio; risk-set sampling; two-stage sampling