Case-control studies in clinical research: mechanism and prevention of selection bias

The mechanism by which selection bias occurs in case-control studies is explained to an audience of clinicians using a simple conceptual framework and a graphical presentation. A case-control study consists in comparing the frequency of exposure in a group of subjects having the studied disease (the cases) relative to another group free of that disease (the controls). Cases and controls can be thought of as arising from a hypothetical cohort study. Thus, enrolled cases are a fraction F1 of the exposed who developed the disease plus a fraction F3 of the unexposed who developed the disease during a given period. Similarly, enrolled controls are a fraction F2 of the exposed who did not develop disease plus a fraction F4 of the unexposed who did not develop the disease. A selection process is inherent to the design of case-control studies but it leads to selection bias only when the ratio of F1 x F4/F2 x F3 is not equal to unity. Examples demonstrate the implication of sampling fractions for designing and interpreting case-control studies performed in clinical settings.