gms | German Medical Science

53. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e. V. (GMDS)

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie

15. bis 18.09.2008, Stuttgart

Meta-analyses with rare outcomes should use adequate methods – A case study from cardiac surgery

Meeting Abstract

Suche in Medline nach

  • Oliver Kuss - Institut für Medizinische Epidemiologie, Biometrie und Informatik, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland
  • Jochen Börgermann - Klinik für Herz- und Thoraxchirurgie, Universitätsklinikum Jena, Jena, Deutschland

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie. 53. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds). Stuttgart, 15.-19.09.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocMBIO1-2

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Veröffentlicht: 10. September 2008

© 2008 Kuss et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction

Meanwhile it is well understood that meta-analyses with rare binary (e.g., adverse events or safety) outcomes should not use the standard fixed-effects (FE) or random-effects (RE) model for inference on treatment effects. This has been theoretically proven [1], [2] and empirically confirmed in several simulation studies [3], [4], [5], [6], [7]. The Mantel-Haenszel (MH) method [8] has been recommended instead in these sparse data situations. However, these recommendations are frequently overlooked. For example, the three largest systematic reviews [9], [10], [11] on the comparison of off-pump and on-pump surgery in coronary artery bypass surgery, one of the most hotly debated and polarizing issues in cardiac surgery [12], all use the standard methods. This is especially problematic as the outcomes most relevant to the patient, postoperative death, stroke, myocardial infarction, or renal failure are observed very rarely, in about 1-2% of the patients.

Material and methods

In a systematic review with the common requirements (prespecified inclusion criteria, reproducible search strategy, two blinded reviewers etc.) we collected all randomized controlled trials (RCTs) comparing off-pump and on-pump surgery in coronary artery bypass surgery. We combined treatment estimates from the single studies for ten clinical outcomes (postoperative death, stroke, myocardial infarction, atrial fibrillation, RBC transfusion, inotrope requirement, wound infection, reoperation for bleeding, renal failure, and IABP support) by computing summary odds ratios [95% confidence intervals] from the FE model, the RE model, and the MH method.

Results

Our initial search yielded 106 publications, of which 57 met the inclusion criteria. These included information from 51 RCTs, 223 single study odds ratios, and 4943 patients. For clinical outcomes which are observed only rarely, the FE and the RE odds ratios always underestimate the treatment effect, in some cases considerably. For example, the FE and the RE odds ratios for postoperative death were 0.94 [0.58, 1.50], but 0.64 [0.36, 1.15] from the MH approach. For postoperative stroke the FE and the RE odds ratios were 0.71 [0.41, 1.23], but 0.50 [0.25, 1.00] from the MH approach.

Discussion

Current meta-analyses for the comparison of off-pump and on-pump surgery in coronary artery bypass surgery underestimate the benefit of the off-pump method, especially for the clinical outcomes which are most relevant to the patient. This is due to the inadequate application of the standard statistical methods. The application of the Mantel-Haenszel method would yield a more realistic picture.


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