Assessing bias in osteoarthritis trials included in Cochrane reviews

Article type
Authors
Bolvig Hansen J1, Juhl C2, Boutron I3, Tugwell P4, Ghogomu E4, Pardo Pardo J4, Rader T4, A. Wells G5, Mayhew A6, Lund H2, Christensen R1
1Musculoskeletal Statistics Unit, The Parker Institute, Dept of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark
2Institute of Sports Science and Clinical Biomechanics, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
3NSERM, University Paris Descartes, Paris, France
4Cochrane Musculoskeletal Group, University of Ottawa, Canada
5Epidemiology and Community Medicine, University of Ottawa, Canada
6Ottawa Hospital Research Institute, Centre for Practice-Changing Research, Ottawa, Canada; Cochrane Bias Methods Group, Canada
Abstract
Introduction:
The validity of reviews and meta-analysis depends upon the 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 and analysis:
Only 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 Cochrane recommendations. Furthermore, single versus multicentre trial status, trial size, and funding will be assessed. The primary outcome (pain) will be abstracted from the first forest plot for overall pain that appears in the Cochrane Review. Treatment effect sizes (ESs) will be expressed as standardised mean differences (SMDs), where the difference in mean values available from the forest plots is divided by the pooled standard deviation (SD). To assess the risk of bias in treatment benefits empirically, 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 (t2, estimated as Tau-squared (T2)) as a consequence of inclusion in the mixed-effects statistical model.

Ethics and dissemination:
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.