title: Advantages of the nested case-control design in diagnostic research.
abstract: BACKGROUND
  Despite its benefits, it is uncommon to apply the nested case-control design in diagnostic research. We aim to show advantages of this design for diagnostic accuracy studies.
  
  
  METHODS
  We used data from a full cross-sectional diagnostic study comprising a cohort of 1295 consecutive patients who were selected on their suspicion of having deep vein thrombosis (DVT). We draw nested case-control samples from the full study population with case:control ratios of 1:1, 1:2, 1:3 and 1:4 (per ratio 100 samples were taken). We calculated diagnostic accuracy estimates for two tests that are used to detect DVT in clinical practice.
  
  
  RESULTS
  Estimates of diagnostic accuracy in the nested case-control samples were very similar to those in the full study population. For example, for each case:control ratio, the positive predictive value of the D-dimer test was 0.30 in the full study population and 0.30 in the nested case-control samples (median of the 100 samples). As expected, variability of the estimates decreased with increasing sample size.
  
  
  CONCLUSIONS
  Our findings support the view that the nested case-control study is a valid and efficient design for diagnostic studies and should also be (re)appraised in current guidelines on diagnostic accuracy research.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. cornelib@chw.edu.au
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Biesheuvel
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Vergouwe
authors.forename: Ruud
authors.initials: R
authors.lastname: Oudega
authors.forename: Arno W
authors.initials: AW
authors.lastname: Hoes
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Karel G M
authors.initials: KG
authors.lastname: Moons
mesh_terms: D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006801:Humans; D012107:Research Design; D012680:Sensitivity and Specificity; D020246:Venous Thrombosis / Q000175:diagnosis*