Received on January 21, 2005
Accepted on May 12, 2005

Minireview

Case-Control and Two-Gate Designs in Diagnostic Accuracy Studies

¹ Departments of Clinical Epidemiology and Biostatistics and Urology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, and Clinical Epidemiology and Biostatistics
² Departments of Clinical Epidemiology and Biostatistics and Urology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, and Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
³ Departments of Clinical Epidemiology and Biostatistics and Urology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, and Urology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

^* To whom correspondence should be addressed. E-mail: a.rutjes{at}amc.uva.nl.

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 criticized for leading to inflated estimates of accuracy.

Methods: We discuss similarities and differences between diagnostic and etiologic case-control studies, as well as the mechanisms that can lead to variation in estimates 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 in nature, whereas etiologic case-control studies aim to quantify the effect of potential causal exposures on disease occurrence. Case-control studies inherently involve 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, which 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: As the accuracy of a test is likely to vary across subgroups of patients, researchers and clinicians might carefully consider the potential for spectrum effects in all designs and analyses, particularly in diagnostic accuracy studies with differential sampling schemes for diseased (cases) and nondiseased individuals (controls).