{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T22:41:26Z","timestamp":1760827286847,"version":"build-2065373602"},"reference-count":30,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002462","name":"Chungnam National University","doi-asserted-by":"publisher","award":["2023-0597-01"],"award-info":[{"award-number":["2023-0597-01"]}],"id":[{"id":"10.13039\/501100002462","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,10,14]]},"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Chronic pain is one of the most common and serious symptoms of cancer. Despite the limitations of dose titration using only one type of opioid, the effects of opioid combinations are poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This study will be conducted in accordance with the Cochrane Handbook of Systematic Reviews of Interventions 6.3. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science databases from their inception to June 2023. This review will consider all clinical trials involving patients aged \u226518 years who received opioids for chronic cancer pain. Two reviewers will independently screen and select relevant studies. The intervention will be a combination of opioids, including both strong and weak, to control cancer pain. The comparator will be set as a single opioid, with or without a placebo. For randomised controlled trials, version 2 of the Cochrane tool will be used to assess the risk of bias. For non-randomised studies, the risk of bias will be assessed using a tool for assessing the Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I). The primary outcome will be pain response; if a quantitative synthesis is not appropriate, a synthesis without a meta-analysis will be undertaken. The quality of evidence for each primary outcome will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation guidelines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>Ethical approval was not required for this systematic review and meta-analysis. The findings will be disseminated through peer-reviewed (open-access) journal publications and conference presentations. Given the widespread use of opioid-based cancer pain management in clinical practice, this study is expected to generate significant interest among physicians, many of whom are likely to review and consider the findings in the context of their clinical decision-making.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PROSPERO registration number<\/jats:title>\n                  <jats:p>PROSPERO CRD42023427299.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-084829","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T03:09:25Z","timestamp":1735009765000},"page":"e084829","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of opioid combination versus single opioid for adult cancer pain: a protocol for systematic review and meta-analysis"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4450-3350","authenticated-orcid":false,"given":"Chi Hoon","family":"Maeng","sequence":"first","affiliation":[{"name":"Division of Medical Oncology and Hematology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Palliative Care & Rehabilitation Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yeon","family":"Kang","sequence":"additional","affiliation":[{"name":"Kyung Hee University Medical Center Library, Kyung Hee University Hospital, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Hallym University College of Medicine, Seoul, Republic of Korea"},{"name":"Department of Family Medicine, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Hye","family":"Kwon","sequence":"additional","affiliation":[{"name":"Division of Hemato-oncology, Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong, Republic of Korea"},{"name":"Division of Hemato-oncology, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"2025101815061234000_14.12.e084829.1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm056"},{"key":"2025101815061234000_14.12.e084829.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2015.12.340"},{"key":"2025101815061234000_14.12.e084829.3","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy152"},{"key":"2025101815061234000_14.12.e084829.4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.52.5188"},{"key":"2025101815061234000_14.12.e084829.5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02198"},{"key":"2025101815061234000_14.12.e084829.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60236-5"},{"key":"2025101815061234000_14.12.e084829.7","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1200\/JCO.2002.20.1.348","article-title":"Opioid rotation in the management of refractory cancer pain","volume":"20","author":"Indelicato","year":"2002","journal-title":"J Clin Oncol"},{"key":"2025101815061234000_14.12.e084829.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2014.05.021"},{"key":"2025101815061234000_14.12.e084829.9","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S315585"},{"key":"2025101815061234000_14.12.e084829.10","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2012.648611"},{"key":"2025101815061234000_14.12.e084829.11","first-page":"189","article-title":"Opioid combination: rationale and possible clinical applications","volume":"2","author":"Mercadante","year":"2013","journal-title":"Ann Palliat Med"},{"key":"2025101815061234000_14.12.e084829.12","doi-asserted-by":"publisher","DOI":"10.1177\/0269216310392101"},{"key":"2025101815061234000_14.12.e084829.13","unstructured":"Julian Higgins JTSe , Chandler J , Cumpston M , et al . 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