Advantages of the nested case-control design in diagnostic research

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.