title: Assessing bias in osteoarthritis trials included in Cochrane reviews: protocol for a meta-epidemiological study.
abstract: BACKGROUND
  The validity of systematic reviews and meta-analysis depends on methodological quality and unbiased dissemination of trials. Our objective is to evaluate the association of estimates of treatment effects with different bias-related study characteristics in meta-analyses of interventions used for treating pain in osteoarthritis (OA). From the findings, we hope to consolidate guidance on interpreting OA trials in systematic reviews based on empirical evidence from Cochrane reviews.
  
  
  METHODS
  Only systematic reviews that compare experimental interventions with sham, placebo or no intervention control will be considered eligible. Bias will be assessed with the risk of bias tool, used according to the Cochrane Collaboration's recommendations. Furthermore, center status, trial size and funding will be assessed. The primary outcome (pain) will be abstracted from the first appearing forest plot for overall pain in the Cochrane review. Treatment effect sizes will be expressed as standardised mean differences (SMDs), where the difference in mean values available from the forest plots is divided by the pooled SD. To empirically assess the risk of bias in treatment benefits, we will perform stratified analyses of the trials from the included meta-analyses and assess the interaction between trial characteristics and treatment effect. A relevant study-level covariate is defined as one that decreases the between-study variance (τ(2), estimated as Tau-squared) as a consequence of inclusion in the mixed effects statistical model.
  
  
  BACKGROUND
  Meta-analyses and randomised controlled trials provide the most reliable basis for treatment of patients with OA, but the actual impact of bias is unclear. This study will systematically examine the methodological quality in OA Cochrane reviews and explore the effect estimates behind possible bias. Since our study does not collect primary data, no formal ethical assessment and informed consent are required.
  
  
  BACKGROUND
  PROSPERO (CRD42013006924).
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Frederiksberg, Copenhagen, Denmark.|SEARCH Research Group, Research Unit of Musculoskeletal Function and Physiotherapy, Institute of Sports Science and Clinical Biomechanics, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Hansen
authors.affiliation: SEARCH Research Group, Research Unit of Musculoskeletal Function and Physiotherapy, Institute of Sports Science and Clinical Biomechanics, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Juhl
authors.affiliation: INSERM, University Paris Descartes, Paris, France.|Cochrane Bias Methods Group, Ottawa, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boutron
authors.affiliation: Ottawa Hospital Research Institute, Joint Coordinating Editor CMSG, Ottawa, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Tugwell
authors.affiliation: Cochrane Musculoskeletal Group, University of Ottawa, Ottawa, Canada.
authors.forename: Elizabeth A T
authors.initials: EAT
authors.lastname: Ghogomu
authors.affiliation: Cochrane Musculoskeletal Group, University of Ottawa, Ottawa, Canada.
authors.forename: Jordi
authors.initials: J
authors.lastname: Pardo Pardo
authors.affiliation: Cochrane Musculoskeletal Group, University of Ottawa, Ottawa, Canada.
authors.forename: Tamara
authors.initials: T
authors.lastname: Rader
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: George A
authors.initials: GA
authors.lastname: Wells
authors.affiliation: Cochrane Bias Methods Group, Ottawa, Canada.|Ottawa Hospital Research Institute, Centre for Practice-Changing Research, Ottawa, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Mayhew
authors.affiliation: Cochrane Musculoskeletal Group, University of Ottawa, Ottawa, Canada.
authors.forename: Lara
authors.initials: L
authors.lastname: Maxwell
authors.affiliation: SEARCH Research Group, Research Unit of Musculoskeletal Function and Physiotherapy, Institute of Sports Science and Clinical Biomechanics, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Lund
authors.affiliation: Musculoskeletal Statistics Unit, Department of Rheumatology, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Frederiksberg, Copenhagen, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
mesh_terms: D018771:Arthralgia / Q000209:etiology / Q000628:therapy*; D015982:Bias; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D016021:Epidemiologic Studies; D006801:Humans; D015201:Meta-Analysis as Topic; D010003:Osteoarthritis / Q000150:complications / Q000628:therapy*; D017594:Publication Bias; D012196:Review Literature as Topic
keywords: meta-analysis; meta-epidemiology; osteoarthritis; risk of bias