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 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. 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, which can lead to changes in 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).
Rutjes
Anne W S
AW
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.rutjes@amc.uva.nl
Reitsma
Johannes B
JB
Vandenbroucke
Jan P
JP
Glas
Afina S
AS
Bossuyt
Patrick M M
PM
D016022:Case-Control Studies; D019411:Clinical Laboratory Techniques / Q000706:statistics & numerical data*; D004194:Disease / Q000209:etiology*; D004812:Epidemiologic Methods; D006801:Humans; D012107:Research Design