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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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Volume 47, Issue 11


Meta-analyses of diagnostic studies

Ton J. Cleophas
  • European Interuniversity College of Pharmaceutical Medicine, Lyon, France
  • Albert Schweitzer Hospital Dordrecht, Dordrecht, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Aeilko H. Zwinderman
  • European Interuniversity College of Pharmaceutical Medicine, Lyon, France
  • Academic Medical Center, Amsterdam, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-10-12 | DOI: https://doi.org/10.1515/CCLM.2009.317


Background: Diagnostic reviews often include the sensitivity/specificity results of individual studies. A problem occurs when these data are pooled because the correlation between sensitivity and specificity is generally strongly negative, causing overestimation of the pooled results. The diagnostic odds ratio (DOR), defined as the odds of true positives vs. that of false positives, may avoid this problem. The aim of the study was to review the advantages and limitations of the DORs.

Methods: A systematic review of 44 previously published diagnostic studies was used as an example.

Results: DORs can be readily implemented in diagnostic research. Advantages include: (1) they adjust for the negative and curvilinear correlations between sensitivities and specificities, (2) they take account of the heterogeneity between studies with respect to the different thresholds chosen by the investigators in the original studies, and (3) it is easy to extend the model with covariates representing between-study differences in design. Limitations include: 1) the outcome parameter is a summary estimate of both sensitivity and specificity, and 2) the magnitude of the studies included is not taken into account.

Conclusions: Reported sensitivities and specificities of different studies assessing similar diagnostic tests are not only negatively correlated, but also negatively correlated in a curvilinear manner. It is appropriate to take this negative curvilinear correlation into account in the data pooling of such meta-analyses. The DORs can be applied for that purpose.

Clin Chem Lab Med 2009;47:1351–4.

Keywords: diagnostic odds ratios; false negative rate; false positive rate; meta-analysis; qualitative diagnostic studies; ROC curves; sensitivity; specificity; summary ROC curves; true negative rate; true positive rate

About the article

Corresponding author: Ton J. Cleophas, MD, PhD, Professor, European College of Pharmaceutical Medicine, Lyon France, c/o Department Medicine Albert Schweitzer Hospital, Dordrecht Netherlands, Box 444, 3300 AK Dordrecht, Netherlands Phone: +31 184 43422, Fax: +31 184 434340,

Received: 2009-06-01

Accepted: 2009-07-24

Published Online: 2009-10-12

Published in Print: 2009-11-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 47, Issue 11, Pages 1351–1354, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2009.317.

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