Systematic Review on Opioid Treatments for Chronic Pain: Surveillance Report 2 (2022)

Background and PurposeThis is the third and final surveillance report for the 2020 report Opioid Treatments for Chronic Pain 1 (https://effectivehealthcare.ahrq.gov/products/opioids-chronic-pain/research),covering the period December 2021 to March 16, 2022.The 2020 report addressed benefits and harms of opioids in patients with chronic pain, opioid dosing strategies, and risk assessment and risk mitigation strategies.Given the clinical and public health importance of this topic, it is important to identify new evidence that could impact practice or policy.The purpose of this update is to identify new evidence published after November 2021 and to determine how the new evidence impacts findings of the 2020 report and Surveillance Reports 1 and 2, which added evidence from August 2019 through November 2021 and were published on the Agency for Healthcare Research and Quality (AHRQ) website (https://effectivehealthcare.ahrq.gov/products/opioids-chronic-pain/research).This is the final surveillance update planned for this topic. ScopeThe scope and eligibility criteria established at the time of the original report 1 were utilized for this surveillance report; no changes were made.The report focused on use of opioids in adults for chronic pain management and addressed the following areas:• The effectiveness and comparative effectiveness (benefits and harms, in Key Questions 1 and 2, respectively) of long-term opioid therapy versus placebo, no opioid therapy, or nonopioid therapy.• The comparative effectiveness and harms of various opioid dosing strategies (Key Question 3).• The accuracy of instruments for predicting risk for opioid overdose, addiction, abuse, or misuse; the effectiveness of risk prediction instruments; the effectiveness of various risk mitigation strategies; and comparative effectiveness of strategies for managing patients with opioid use disorder (Key Question 4).The full protocol for the original report, including detailed inclusion criteria using the PICOTS (populations, interventions, comparators, outcomes, timing, settings) framework (https://www.ncbi.nlm.nih.gov/books/NBK556255/table/ch4.tab1) and full Key Questions (https://www.ncbi.nlm.nih.gov/books/n/cer229/ch3/#ch3.s2), are also available on the AHRQ website (https://effectivehealthcare.ahrq.gov/topics/opioids-chronic-pain/protocol)and on the PROSPERO systematic reviews registry (CRD42019127423). MethodsUpdate searches were conducted to identify evidence published after November 2021 through March 16, 2022.Search strategies from the original report were utilized. 1In addition, to capture articles not yet indexed in Medline ® , we supplemented the original search strategies with a previously developed 2 optimized (text-word only) search in pre-Medline to identify new studies not yet indexed with Medical Subject Headings (MeSH).As in the original report, searches on electronic databases were supplemented by review of reference lists of relevant articles.Search strategies are available in Appendix A.As in the original review, one investigator screened citations identified through searches for eligibility for full-text review.(Key Questions and inclusion criteria are available in Appendix B.) In addition, a second investigator utilized a machine learning classifier to assist in the screening.The machine learning classifier screened all citations; the second investigator reviewed all studies that the machine learning classifier did not classify as very low probability of inclusion.The machine learning classifier was previously shown to have 100 percent recall for identifying eligible studies in update searches for this review. 2Any citation identified as potentially eligible by either of the two investigators underwent full-text review to determine final eligibility.We utilized the same methods for data abstraction and quality assessment as for the original report.Studies with at least 1 month of followup were included, and results were stratified according to short-term (1 to <6 months), intermediate term (6 to <12 months), and long-term (≥12 months) followup.We also classified the magnitude of effects for pain and function using the same approach as the original report.A small effect was defined for pain as a mean betweengroup difference following treatment of 0.5 to 1.0 points on a 0-to 10-point numeric rating scale or visual analog scale (VAS) and for function as a standardized mean difference (SMD) of 0.2 to 0.5 or a mean difference of 5 to 10 points on the 0 to 100-point Oswestry Disability Index (ODI), 1 to 2 points on the 0 to 24-point Roland-Morris Disability Questionnaire (RDQ), or equivalent.A moderate effect was defined for pain as a mean difference of 10 to 20 points on a 0-to 100point VAS and for function as an SMD of 0.5 to 0.8, or a mean difference of 10 to 20 points on the ODI, 2 to 5 points on the RDQ, or equivalent.Large/substantial effects were defined as greater than moderate.As in prior surveillance reports, the decision to update meta-analyses from the original report was based on the number and sample sizes of new studies eligible for meta-analysis (metaanalysis performed if new evidence was large relative to the studies in the original metaanalysis); consistency in findings between the new studies and the original meta-analysis (metaanalysis performed if findings from new evidence appear inconsistent and new studies were appropriate for pooling based on similarity in populations, interventions, and comparisons, in order to determine whether new studies impact conclusions); or whether new evidence could impact the strength of evidence (meta-analysis performed if the strength of evidence based on the original meta-analysis was low or insufficient and new evidence could increase the strength of evidence due to increased precision, high quality, or other factors).In addition, because this is the final surveillance update, meta-analyses for comparisons involving opioid versus placebo were updated with new evidence from all three surveillance reports even if they did not meet the updating criteria.We also planned to update meta-analyses for the primary outcomes of pain and function for other comparisons; however, no new studies suitable for pooling were identified for non-placebo comparisons.The strength of evidence was based on the totality of evidence (evidence in the original report plus new evidence from all surveillance updates) and determined using the methods described in the original report.Changes in the strength of evidence assessments resulting from this current surveillance update are described separately from the findings reported in Surveillance Reports 1 and 2. In addition, a table detailing updated strength of evidence assessments with new evidence from all three surveillance reports is provided.A comprehensive list of included studies identified for all three surveillance report periods is provided in Appendix C. Evidence tables providing data from these included studies are available in Appendix D, and quality assessments for each of these studies are shown in Appendix E. Updated meta-analyses are included in Appendix F, and updated strength of evidence tables for outcomes with new evidence are available in Appendix G.A list of articles excluded at full-text review, along with reasons for exclusion, is available in Appendix H. ResultsThe search for Surveillance Report 3 from December 2021 through March 16, 2022, yielded 448 citations; of these, 3 new studies 3-5 met inclusion criteria (2 randomized controlled trials [RCTs] and 1 observational study); in addition, one older placebo-controlled trial 6 of opioids in patients with osteoarthritis that met inclusion criteria was identified from reference list review (Figure 1).One of the new trials 5 was placebo controlled and evaluated opioids for chronic low back pain, and the other new trial 4 compared transcutaneous electrical nerve stimulation (TENS) versus opioids for chronic knee osteoarthritis pain (Appendix D, Table D-1).The observational study compared involuntary opioid reduction, voluntary opioid reduction, and no opioid reduction in patients with chronic pain 3 (Appendix D, Table D-2).Key Question Conclusions From 2020 Report Findings From Surveillance Assessment KQ 2a.Opioids vs. placebo, short-term harms Opioids associated with increased risk of withdrawal due to adverse events, nausea, vomiting, constipation, dizziness, somnolence, pruritus • SOE: High, based on 30 to 60 RCTs