Background: In some diagnostic accuracy studies the test results of a series of patients with an established diagnosis are compared with those of a control group. Such case-control designs are intuitively appealing but they have also been criticised for leading to inflated estimates of accuracy.

Objective and Methods: To discuss the similarities and differences between diagnostic and etiologic case-control studies, and to discuss the mechanisms that can lead to variation in estimates of diagnostic accuracy in studies with separate sampling schemes ('gates') for diseased (cases) and non-diseased subjects (controls).

Results: Diagnostic accuracy studies are cross-sectional and descriptive in nature, while etiologic case-control studies aim to quantify the effect of potential causal exposures on disease occurrence which inherently involves a time window between exposure and disease occurrence. Researchers and readers should be aware of spectrum effects in diagnostic case-control studies as a result of the restricted sampling of cases and/or controls, as this can lead to biased estimates of diagnostic accuracy. These spectrum effects may be advantageous in the early investigation of a new diagnostic test but for an overall evaluation of the clinical performance of a test, case-control studies should closely mimic cross-sectional diagnostic studies.

Conclusions and implications: As the accuracy of a test is likely to vary across subgroups of patients, researchers and clinicians should carefully consider the potential for spectrum effects in all designs and analyses, in particular in diagnostic accuracy studies with differential sampling schemes for diseased (cases) and non-diseased subjects (controls).