Research article

Advantages of the nested case-control design in diagnostic research

Cornelis J Biesheuvel^1,2 , Yvonne Vergouwe¹ , Ruud Oudega¹ , Arno W Hoes¹ , Diederick E Grobbee¹ and Karel GM Moons¹

¹  Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands

²  The Children's Hospital at Westmead, Sydney, Australia

author email corresponding author email

BMC Medical Research Methodology 2008, 8:48doi:10.1186/1471-2288-8-48

Published:	21 July 2008

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.

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.