Case-population studies in pharmacoepidemiology

The case-population approach aims at providing a risk estimate by comparing the incidence of the disease of interest among those exposed to the drug under study with the incidence among the non-exposed. For that purpose, the cases with the disease of interest have to be ascertained independently of the exposure status. Their rate and pattern of exposure have to be ascertained by interview with a structured questionnaire. Information on the patterns and the prevalence of drug consumption is needed in order to estimate the rate of exposure, and drug consumption statistics can be used to this end. In this paper, we review the main characteristics of studies using this approach or a similar one, and studies where series of cases exposed to the drug of interest were compared with drug consumption statistics. We looked at selected basic methodological requirements. Most of the studies reviewed suffer from incomplete case ascertainment, inaccurate definition of the disease of interest, incomplete information on exposures and other risk factors, and/or limited control of potential confounding, among other limitations. All the reviewed studies had several limitations regarding the estimation of the population at risk. The methods used in case-population studies should be clearly described, particularly with respect to the identification of the cases (numerator) and the estimation of the consumption prevalence (denominator). Case-population studies can give approximate risk estimates, but the method should be validated by comparing its results with those of case-control studies.