Advantages of the nested case-control design in diagnostic research

BMC Med Res Methodol. 2008 Jul 21:8:48. doi: 10.1186/1471-2288-8-48.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies*
  • Cross-Sectional Studies
  • Humans
  • Research Design*
  • Sensitivity and Specificity
  • Venous Thrombosis / diagnosis*