Case-control and two-gate designs in diagnostic accuracy studies

BACKGROUND: In some diagnostic accuracy studies, the test results of a series of patients with an established diagnosis are compared with those of a controlgroup. Such case-control designs are intuitively appealing, but they have alsobeen criticized for leading to inflated estimates of accuracy.METHODS: We discuss similarities and differences between diagnostic and etiologiccase-control studies, as well as the mechanisms that can lead to variation inestimates of diagnostic accuracy in studies with separate sampling schemes("gates") for diseased (cases) and nondiseased individuals (controls).RESULTS: Diagnostic accuracy studies are cross-sectional and descriptive innature. Etiologic case-control studies aim to quantify the effect of potentialcausal exposures on disease occurrence, which inherently involves a time windowbetween exposure and disease occurrence. Researchers and readers should be aware of spectrum effects in diagnostic case-control studies as a result of therestricted sampling of cases and/or controls, which can lead to changes inestimates of diagnostic accuracy. These spectrum effects may be advantageous inthe early investigation of a new diagnostic test, but for an overall evaluationof the clinical performance of a test, case-control studies should closely mimic cross-sectional diagnostic studies.CONCLUSIONS: As the accuracy of a test is likely to vary across subgroups ofpatients, researchers and clinicians might carefully consider the potential forspectrum effects in all designs and analyses, particularly in diagnostic accuracystudies with differential sampling schemes for diseased (cases) and nondiseasedindividuals (controls).