{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:47:44Z","timestamp":1788922064765,"version":"build-2803163510"},"reference-count":93,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"unspecified","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000008","name":"Health Canada","doi-asserted-by":"publisher","award":["1819-HQ-000036"],"award-info":[{"award-number":["1819-HQ-000036"]}],"id":[{"id":"10.13039\/501100000008","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,7,24]]},"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Despite a recent meta-analysis including 31 randomised controlled trials comparing methadone and buprenorphine for the treatment of opioid use disorder, important knowledge gaps remain regarding the long-term effectiveness of different treatment modalities across individuals, including rigorously collected data on retention rates and other treatment outcomes. Evidence from real-world data represents a valuable opportunity to improve personalised treatment and patient-centred guidelines for vulnerable populations and inform strategies to reduce opioid-related mortality. Our objective is to determine the comparative effectiveness of methadone versus buprenorphine\/naloxone, both overall and within key populations, in a setting where both medications are simultaneously available in office-based practices and specialised clinics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We propose a retrospective cohort study of all adults living in British Columbia receiving opioid agonist treatment (OAT) with methadone or buprenorphine\/naloxone between 1 January 2008 and 30 September 2018. The study will draw on seven linked population-level administrative databases. The primary outcomes include retention in OAT and all-cause mortality. We will determine the effectiveness of buprenorphine\/naloxone vs methadone using intention-to-treat and per-protocol analyses\u2014the former emulating flexible-dose trials and the latter focusing on the comparison of the two medication regimens offered at the optimal dose. Sensitivity analyses will be used to assess the robustness of results to heterogeneity in the patient population and threats to internal validity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The protocol, cohort creation and analysis plan have been approved and classified as a quality improvement initiative exempt from ethical review (Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics). Dissemination is planned via conferences and publications, and through direct engagement and collaboration with entities that issue clinical guidelines, such as professional medical societies and public health organisations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-036102","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T03:47:43Z","timestamp":1599709663000},"page":"e036102","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Comparative effectiveness of buprenorphine-naloxone versus methadone for treatment of opioid use disorder: a population-based observational study protocol in British Columbia, Canada"],"prefix":"10.1136","volume":"10","author":[{"given":"Micah","family":"Piske","sequence":"first","affiliation":[{"name":"Epidemiology and Population Health Program, BC Centre for Excellence in HIV\/AIDS, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Thomson","sequence":"additional","affiliation":[{"name":"Epidemiology and Population Health Program, BC Centre for Excellence in HIV\/AIDS, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Krebs","sequence":"additional","affiliation":[{"name":"Epidemiology and Population Health Program, BC Centre for Excellence in HIV\/AIDS, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natt","family":"Hongdilokkul","sequence":"additional","affiliation":[{"name":"Epidemiology and Population Health Program, BC Centre for Excellence in HIV\/AIDS, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bruneau","sequence":"additional","affiliation":[{"name":"Centre hospitalier de l'Universit\u00e9 de Montr\u00e9al, CRCHUM, Montreal, Quebec, Canada"},{"name":"D\u00e9partement de m\u00e9decine de famille et de m\u00e9decine d'urgence, Universite de Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"Greenland","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Department of Statistics, UCLA, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gustafson","sequence":"additional","affiliation":[{"name":"Department of Statistics, UBC, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Ehsan","family":"Karim","sequence":"additional","affiliation":[{"name":"School of Population and Public Health, UBC, Vancouver, British Columbia, Canada"},{"name":"Providence Health Care Research Institute, Centre for Health Evaluation and Outcome Sciences, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence C","family":"McCandless","sequence":"additional","affiliation":[{"name":"Department of Statstics and Actuarial Sciences, Simon Fraser University, Burnaby, British Columbia, Canada"},{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Maclure","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology and Therapeutics, UBC, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada"},{"name":"Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Siebert","sequence":"additional","affiliation":[{"name":"Department of Health Policy and Management, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA"},{"name":"Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - 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