Background: Opioids are prescribed frequently and increasingly for the management of chronic non-cancer pain (CNCP). Current systematic reviews have a number of limitations, leaving uncertainty with regard to the benefits and harms associated with opioid therapy for CNCP. We propose to conduct a systematic review and meta-analysis to summarize the evidence for using opioids in the treatment of CNCP and the risk of associated adverse events.
Methods and design: Eligible trials will include those that randomly allocate patients with CNCP to treatment with any opioid or any non-opioid control group. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to evaluate confidence in the evidence on an outcome-by-outcome basis. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. To ensure interpretability of our results, we will present risk differences and measures of relative effect for all outcomes reported and these will be based on anchor-based minimally important clinical differences, when available. We will conduct a priori defined subgroup analyses consistent with current best practices.
Discussion: Our review will evaluate both the effectiveness and the adverse events associated with opioid use for CNCP, evaluate confidence in the evidence using the GRADE approach, and prioritize patient-important outcomes with a focus on functional gains guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with CNCP and identify key areas for future research.
Trial registration: Our protocol is registered on PROSPERO (CRD42012003023), http://www.crd.york.ac.uk/PROSPERO.