A review of analysis methods for secondary outcomes in case-control studies

Abstract

The main goal of a case-control study is to learn the association between various risk factors and a primary outcome (e.g., disease status). Particularly recently, it is also quite common to perform secondary analyses of the case-control data in order to understand certain associations between the risk factors of the primary outcome. It has been repeatedly documented with case-control data, association studies of the risk factors that ignore the case-control sampling scheme can produce highly biased estimates of the population effects. In this article, we review the issues of the naive secondary analyses that do not account for the biased sampling scheme, and also the various methods that have been proposed to account for the case-control ascertainment. We additionally compare the results of many of the discussed methods in an example examining the association of a particular genetic variant with smoking behavior, where the data were obtained from a lung cancer case-control study.