title: [GRADE guidelines: 4. Rating the quality of evidence - limitations of clinical trials (risk of bias)].
abstract: In the GRADE approach, randomised trials start as high-quality evidence and observational studies as low-quality evidence, but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias. Well-established limitations of randomised trials include failure to conceal allocation, failure to blind, loss to follow-up, and failure to appropriately consider the intention-to-treat principle. More recently, recognised limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results. Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance. Risk of bias may vary across outcomes (e.g., loss to follow-up may be far less for all-cause mortality than for quality of life), a consideration that many systematic reviews ignore. In deciding whether to rate down for risk of bias - whether for randomised trials or observational studies-authors should not take an approach that averages across studies. Rather, for any individual outcome, when there are some studies with a high risk, and some with a low risk of bias, they should consider including only the studies with a lower risk of bias.
authors.affiliation: Deutsches Cochrane Zentrum, Institut für Medizinische Biometrie und Medizinische Informatik, Universitätsklinikum FreiburgundKlinik IV. meerpohl@cochrane.de
authors.forename: Joerg J
authors.initials: JJ
authors.lastname: Meerpohl
authors.forename: Gero
authors.initials: G
authors.lastname: Langer
authors.forename: Matthias
authors.initials: M
authors.lastname: Perleth
authors.forename: Gerald
authors.initials: G
authors.lastname: Gartlehner
authors.forename: Angela
authors.initials: A
authors.lastname: Kaminski-Hartenthaler
authors.forename: Holger
authors.initials: H
authors.lastname: Schünemann
mesh_terms: D015982:Bias; D057239:Early Termination of Clinical Trials / Q000592:standards; D023381:Endpoint Determination / Q000592:standards; D019317:Evidence-Based Medicine / Q000592:standards*; D005858:Germany; D019983:Guideline Adherence / Q000592:standards*; D015276:Health Care Rationing / Q000592:standards*; D006801:Humans; D057194:Intention to Treat Analysis / Q000592:standards; D009313:National Health Programs / Q000592:standards*; D011379:Prognosis; D011785:Quality Assurance, Health Care / Q000592:standards*; D016032:Randomized Controlled Trials as Topic / Q000592:standards*