How does the risk of bias influence the effect sizes of exercise therapy in chronic low back pain randomised controlled trials? A protocol for a meta-epidemiological study.

Background and ObjectivesRisk of bias is a critical issue to consider when appraising studies. Generally, the higher the risk of bias of a study, the less confidence there will be that the results are valid. Considering that low back pain is recognized to have an extremely high disease burden; exercise therapy is one of the most frequently prescribed interventions for chronic low back pain (CLBP) and that most low back pain trials have methodological limitations that could bias treatment effect estimates; the objective of this study is to explore causal pathways between the sources of risk of bias and estimates of the treatment effect of exercise therapy interventions in CLBP trials. MethodsThe 249 RCTs included in the 2021 Cochrane review publication "Exercise therapy for chronic low back pain" will be included. The risk of bias will be evaluated with the Cochrane Risk of Bias 2 tool (ROB 2). Causal pathways between the exposure (risk of bias domains) and our outcomes of interest (effect sizes for pain and functional limitations) will be explored through univariable and multivariable meta-regression models. These models will be adjusted for potential confounders (sample size, trial registration, incomplete flow chart information and treatment comparisons), exploring relevant interactions within each model. Additional and sensitivity analyses will be performed to explore and test the robustness of the primary analyses. Ethics and disseminationA manuscript will be prepared and submitted for publication in an appropriate peer-reviewed journal upon study completion. We believe that the results of this investigation will be relevant to researchers paying more attention to the synthesis of the evidence to translate clinical implications to key stakeholders (healthcare providers and patients).