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 fractionF1of the exposed who developed the disease plus a fractionF3of the unexposed who developed the disease during a given period. Similarly, enrolled controls are a fractionF2of the exposed who did not develop disease plus a fractionF4of 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 ofF1×F4/F2×F3is not equal to unity. Examples demonstrate the implication of sampling fractions for designing and interpreting case-control studies performed in clinical settings.