Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews

Systematic Reviews, May 2016

Background The Cochrane risk of bias tool for randomized clinical trials was introduced in 2008 and has frequently been commented on and used in systematic reviews. We wanted to evaluate the tool by reviewing published comments on its strengths and challenges and by describing and analysing how the tool is applied to both Cochrane and non-Cochrane systematic reviews. Methods A review of published comments (searches in PubMed, The Cochrane Methodology Register and Google Scholar) and an observational study (100 Cochrane and 100 non-Cochrane reviews from 2014). Results Our review included 68 comments, 15 of which were categorised as major. The main strengths of the tool were considered to be its aim (to assess trial conduct and not reporting), its developmental basis (wide consultation, empirical and theoretical evidence) and its transparent procedures. The challenges of the tool were mainly considered to be its choice of core bias domains (e.g. not involving funding/conflicts of interest) and issues to do with implementation (i.e. modest inter-rater agreement) and terminology. Our observational study found that the tool was used in all Cochrane reviews (100/100) and was the preferred tool in non-Cochrane reviews (31/100). Both types of reviews frequently implemented the tool in non-recommended ways. Most Cochrane reviews planned to use risk of bias assessments as basis for sensitivity analyses (70 %), but only a minority conducted such analyses (19 %) because, in many cases, few trials were assessed as having “low” risk of bias for all standard domains (6 %). The judgement of at least one risk of bias domain as “unclear” was found in 89 % of included randomized clinical trials (1103/1242). Conclusions The Cochrane tool has become the standard approach to assess risk of bias in randomized clinical trials but is frequently implemented in a non-recommended way. Based on published comments and how it is applied in practice in systematic reviews, the tool may be further improved by a revised structure and more focused guidance.

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Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews

Jørgensen et al. Systematic Reviews Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews Lars Jørgensen 2 Asger S. Paludan-Müller 2 David R. T. Laursen 2 Jelena Savović 0 1 Isabelle Boutron 4 Jonathan A. C. Sterne 0 1 Julian P. T. Higgins 0 1 Asbjørn Hróbjartsson 2 3 0 The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West (NIHR CLAHRC West) at University Hospitals Bristol NHS Foundation Trust , Bristol , UK 1 School of Social and Community Medicine, University of Bristol , Canynge Hall, 39 Whatley Road, Bristol BS8 2PS , UK 2 The Nordic Cochrane Centre , Rigshospitalet 7811, Blegdamsvej 9, 2100 Copenhagen , Denmark 3 Research Unit for Evidence-Based Medicine, University of Southern Denmark , Odense , Denmark 4 Methods of Therapeutic Evaluation of Chronic Diseases Team, Epidemiology and Biostatistics, Sorbonne Paris Cité Research Centre, L'Institut National de la Santé et de la Recherche Médicale, Unite Mixte de Recherche 1153 , Paris , France Background: The Cochrane risk of bias tool for randomized clinical trials was introduced in 2008 and has frequently been commented on and used in systematic reviews. We wanted to evaluate the tool by reviewing published comments on its strengths and challenges and by describing and analysing how the tool is applied to both Cochrane and non-Cochrane systematic reviews. Methods: A review of published comments (searches in PubMed, The Cochrane Methodology Register and Google Scholar) and an observational study (100 Cochrane and 100 non-Cochrane reviews from 2014). Results: Our review included 68 comments, 15 of which were categorised as major. The main strengths of the tool were considered to be its aim (to assess trial conduct and not reporting), its developmental basis (wide consultation, empirical and theoretical evidence) and its transparent procedures. The challenges of the tool were mainly considered to be its choice of core bias domains (e.g. not involving funding/conflicts of interest) and issues to do with implementation (i.e. modest inter-rater agreement) and terminology. Our observational study found that the tool was used in all Cochrane reviews (100/100) and was the preferred tool in non-Cochrane reviews (31/100). Both types of reviews frequently implemented the tool in non-recommended ways. Most Cochrane reviews planned to use risk of bias assessments as basis for sensitivity analyses (70 %), but only a minority conducted such analyses (19 %) because, in many cases, few trials were assessed as having “low” risk of bias for all standard domains (6 %). The judgement of at least one risk of bias domain as “unclear” was found in 89 % of included randomized clinical trials (1103/1242). Conclusions: The Cochrane tool has become the standard approach to assess risk of bias in randomized clinical trials but is frequently implemented in a non-recommended way. Based on published comments and how it is applied in practice in systematic reviews, the tool may be further improved by a revised structure and more focused guidance. Cochrane; Systematic review; Bias; Tool; Comment; User practice; Randomized clinical trial Background Since the early 1990s, the number of published systematic reviews of randomized trials, both Cochrane and non-Cochrane reviews, has steadily increased. The ideal of taking a systematic approach to identify, summarise and analyse comparable clinical trials as a basis for therapeutic decisions has become more widespread, and systematic reviews have had a huge impact on clinical research and practice. However, one obstacle to the usefulness of a systematic review is the possibility that some of the included trials are biased due to flaws in their design, conduct, analysis or reporting. A meta-analysis of biased effect estimates will likely produce a biased pooled analysis with increased precision and greater credibility. Thus, for authors of a systematic review, it is paramount to adequately address the risk of bias in the included trials [ 1 ]. For this purpose, the Cochrane tool for assessing risk of bias in randomized clinical trials (i.e. the tool) was released in 2008 and updated in 2011. The tool is based on seven bias domains: sequence generation and allocation concealment (both within the domain of selection bias or allocation bias), blinding of participants and personnel (performance bias), blinding of outcome assessors (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias) and an auxiliary domain: “other bias.” For each bias domain, the tool urges users to assign a judgement of “high,” “low” or “unclear” risk of bias and to document the basis for their judgements (e.g. with verbatim quotes). The bias domains of the tool were selected with the intention to cover all fundamental bias mechanisms in (...truncated)


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Lars Jørgensen, Asger Paludan-Müller, David Laursen, Jelena Savović, Isabelle Boutron, Jonathan Sterne, Julian Higgins, Asbjørn Hróbjartsson. Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews, Systematic Reviews, 2016, pp. 80, 5, DOI: 10.1186/s13643-016-0259-8