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Individual patient data meta-analysis for the clinical assessment of coronary computed tomography angiography: protocol of the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT)

Georg M Schuetz1, Peter Schlattmann2, Stephan Achenbach3, Matthew Budoff4, Mario J Garcia5, Robert Roehle1, Gianluca Pontone6, Willem Bob Meijboom7, Daniele Andreini6, Hatem Alkadhi8, Lily Honoris4, Nuno Bettencourt9, Jörg Hausleiter10, Sebastian Leschka11, Bernhard L Gerber12, Matthijs FL Meijs13, Abbas Arjmand Shabestari14, Akira Sato15, Elke Zimmermann1, Uwe J Schoepf16, Axel Diederichsen17, David A Halon18, Vladimir Mendoza-Rodriguez19, Ashraf Hamdan2021, Bjarne L Nørgaard22, Harald Brodoefel23, Kristian A Øvrehus24, Shona MM Jenkins25, Bjørn A Halvorsen26, Johannes Rixe27, Mehraj Sheikh28, Christoph Langer2930, Eugenio Martuscelli31, Andrea Romagnoli32, Arthur JHA Scholte33, Roy P Marcus34, Geir R Ulimoen35, Koen Nieman367, Hans Mickley17, Konstantin Nikolaou34, Jean-Claude Tardif37, Thorsten RC Johnson34, Simone Muraglia38, Benjamin JW Chow39, David Maintz4041, Michael Laule42 and Marc Dewey1*

Author Affiliations

1 Department of Radiology, Charité - Universitätsmedizin Berlin Campus Mitte, Humboldt-Universität zu Berlin, Freie Universität Berlin, Charitéplatz 1, Berlin 10117, Germany

2 Department of Medical Statistics, Informatics and Documentation (PS), University Hospital of Friedrich Schiller University Jena, Jena, Germany

3 Medizinische Klinik 2, Universitätsklinikum Erlangen, Ulmenweg 18, Erlangen, 91054, Germany

4 Los Angeles Biomedical Research Institute, 1124 W Carson Street, Torrance, CA, 90502, USA

5 Division of Cardiology, Montefiore Medical Center - Albert Einstein College of Medicine, 211 East 210th Street, Bronx, NY, 10467, USA

6 Centro Cardiologico Monzino, IRCCS, Via C. Parea 4, Milan, 20134, Italy

7 Department of Cardiology, Erasmus Medical Center, ‘s Gravendijkwal 230, Postbus 2040, Rotterdam, CA, 3000, The Netherlands

8 Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland

9 Cardiovascular CT and Cardiac Magnetic Resonance Laboratory, Cardiovascular Diagnostic and Intervention Unit - Department of Cardiology, Centro Hospitalar de Vila Nova de Gaia Hospita, Rua Conceição Fernandes, V.N. Gaia, 4434-502, Portugal

10 Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter, Deutsches Herzzentrum München, Klinik an der Technischen Universität München, München, Germany

11 Institute of Radiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, St. Gallen, 9007, Switzerland

12 Department of Cardiology, Cliniques Universitaires St. Luc, Universite Catholique de Louvain, Brussels, Belgium

13 Department of Cardiology, University Medical Center Utrecht, H 100, 3584 CX,, Utrecht, HP E03.511, The Netherlands

14 Department of Radiology, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

15 Cardiovascular Division, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

16 Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA

17 Department of Cardiology, Odense University Hospital, Sdr. Boulevard 29, Odense C, 5000, Denmark

18 Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel

19 National Institute of Cardiology and Cardiovascular Surgery, ”Manuel Fajardo” Medical Sciences Faculty, Medical Sciences University of Havana, Tomography Department, Vedado, Plaza de La Revoluciòn, The Havana, Cuba

20 Department of Internal Medicine/Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany

21 Heart Center, Chaim Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Tel Hashomer, Israel

22 Department of Cardiology B, Aarhus University Hospital Skejby, Aarhus N, DK- 8200, Denmark

23 University Department of Radiology, University Hospital Tübingen, Hoppe-Seyler-Straße 3, Tübingen, 72076, Germany

24 Department of Cardiology, Vejle Hospital, Vejle, Denmark

25 Department of Cardiology, Glasgow Royal Infirmary, Glasgow, UK

26 Department of Cardiology, Ostfold County Hospital, Fredrikstad, N-1603, Norway

27 Medizinische Klinik I (Kardiologie, Angiologie), Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen, Klinikstr. 33, Giessen, 35392, Germany

28 Department of Radiology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat, 13110, Kuwait

29 Klinik für Innere Medizin III mit Schwerpunkt Kardiologie und Angiologie, UKSH, Campus Kiel, Schittenhelmstr. 12, Kiel, D-24105, Germany

30 Kardiologische Klinik, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Georgstr. 11, Bad Oeynhausen, 32545, Germany

31 Division of Cardiology, Department of Internal Medicine, University of Rome Tor Vergata, Viale Oxford 81, Rome, 00133, Italy

32 Department of Radiology, University of Rome Tor Vergata, Viale Oxford 81, Rome, 00133, Italy

33 Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300, RC Leiden, the Netherlands

34 Department of Clinical Radiology, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, Munich, 81377, Germany

35 Department of Radiology, Akershus University Hospital, Lorenskog, Norway

36 Department of Radiology, Erasmus University Medical Center, 's Gravendijkwal 230, Rotterdam, CE, 3015, The Netherlands

37 Montreal Heart Institute, Université de Montréal, 5000 Belanger Street, Montreal, PQ H1T 1C8, Canada

38 Department of Cardiology, S. Chiara Hospital, L.go Medaglie d’Oro 1, Trento, 38100, Italy

39 University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada

40 Department of Radiology, University of Cologne, Kerpener Str. 62, Köln, 50937, Germany

41 Department of Radiology, University of Münster, Albert-Schweitzer-Campus 1, Münster, 48149, Germany

42 Department of Cardiology, Charité – Universitätsmedizin Berlin Campus Mitte, Humboldt-Universität zu Berlin, Freie Universität Berlin, Charitéplatz 1, Berlin, 10117, Germany

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Systematic Reviews 2013, 2:13  doi:10.1186/2046-4053-2-13

Published: 15 February 2013



Coronary computed tomography angiography has become the foremost noninvasive imaging modality of the coronary arteries and is used as an alternative to the reference standard, conventional coronary angiography, for direct visualization and detection of coronary artery stenoses in patients with suspected coronary artery disease. Nevertheless, there is considerable debate regarding the optimal target population to maximize clinical performance and patient benefit. The most obvious indication for noninvasive coronary computed tomography angiography in patients with suspected coronary artery disease would be to reliably exclude significant stenosis and, thus, avoid unnecessary invasive conventional coronary angiography. To do this, a test should have, at clinically appropriate pretest likelihoods, minimal false-negative outcomes resulting in a high negative predictive value. However, little is known about the influence of patient characteristics on the clinical predictive values of coronary computed tomography angiography. Previous regular systematic reviews and meta-analyses had to rely on limited summary patient cohort data offered by primary studies. Performing an individual patient data meta-analysis will enable a much more detailed and powerful analysis and thus increase representativeness and generalizability of the results. The individual patient data meta-analysis is registered with the PROSPERO database (CoMe-CCT, CRD42012002780).


The analysis will include individual patient data from published and unpublished prospective diagnostic accuracy studies comparing coronary computed tomography angiography with conventional coronary angiography. These studies will be identified performing a systematic search in several electronic databases. Corresponding authors will be contacted and asked to provide obligatory and additional data. Risk factors, previous test results and symptoms of individual patients will be used to estimate the pretest likelihood of coronary artery disease. A bivariate random-effects model will be used to calculate pooled mean negative and positive predictive values as well as sensitivity and specificity. The primary outcome of interest will be positive and negative predictive values of coronary computed tomography angiography for the presence of coronary artery disease as a function of pretest likelihood of coronary artery disease, analyzed by meta-regression. As a secondary endpoint, factors that may influence the diagnostic performance and clinical value of computed tomography, such as heart rate and body mass index of patients, number of detector rows, and administration of beta blockade and nitroglycerin, will be investigated by integrating them as further covariates into the bivariate random-effects model.


This collaborative individual patient data meta-analysis should provide answers to the pivotal question of which patients benefit most from noninvasive coronary computed tomography angiography and thus help to adequately select the right patients for this test.

Collaborative meta-analysis on cardiac CT; CoMe-CCT; Coronary CT angiography; Individual patient data meta-analysis; IPD; Positive and negative predictive value; Pretest likelihood; Sensitivity and specificity; Study protocol