{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:50:09Z","timestamp":1788922209680,"version":"build-2803163510"},"reference-count":127,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institutes on Drug Abuse","doi-asserted-by":"crossref","award":["R01DA050629"],"award-info":[{"award-number":["R01DA050629"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,7,22]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Selecting an optimal initial dosage of opioid agonist treatment (OAT) balances effectiveness and safety, as initial doses that are too low may be insufficient, potentially prompting clients to seek unregulated drugs to alleviate withdrawal symptoms, which may increase the likelihood of treatment discontinuation. Conversely, initial doses that are too high carry a risk of overdose. As opioid tolerance levels have risen in the fentanyl era, linked population-level data capturing initial doses in the real world provide a valuable opportunity to refine existing guidance on optimal OAT dosing at treatment initiation. Our objective is to determine the comparative effectiveness of alternative initial doses of methadone, buprenorphine-naloxone and slow-release oral morphine at OAT initiation, as observed in clinical practice in British Columbia (BC), Canada.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>We propose a population-level retrospective observational study with a linkage of nine provincial health administrative databases in BC, Canada (1 January 2010 to 31 December 2022). Our study includes two time-to-event primary outcomes: OAT discontinuation and all-cause mortality during follow-up. We propose \u2018initiator\u2019 target trial analyses for each medication using both propensity score weighting and instrumental variable analyses to compare the effect of different initial OAT doses on the hazard of time-to-OAT discontinuation and all-cause mortality. A range of sensitivity analyses will be used to assess the robustness of the results.<\/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 classified and approved as a quality improvement initiative by Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups and decision-makers, national and international clinical guideline developers, presented at international conferences and published in peer-reviewed journals electronically and in print.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-098990","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T16:30:24Z","timestamp":1756744224000},"page":"e098990","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Comparative effectiveness of alternative initial doses of opioid agonist treatment for individuals with opioid use disorder: a protocol for a retrospective population-based study using target trial emulation in British Columbia, Canada"],"prefix":"10.1136","volume":"15","author":[{"given":"Ruyu","family":"Yan","sequence":"first","affiliation":[{"name":"Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada"},{"name":"Faculty of health science, Simon Fraser University, Burnaby, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-863X","authenticated-orcid":false,"given":"Md Belal","family":"Hossain","sequence":"additional","affiliation":[{"name":"Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada"},{"name":"School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-722X","authenticated-orcid":false,"given":"Jeong Eun","family":"Min","sequence":"additional","affiliation":[{"name":"Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Kurz","sequence":"additional","affiliation":[{"name":"Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keara","family":"Smith","sequence":"additional","affiliation":[{"name":"Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Piske","sequence":"additional","affiliation":[{"name":"Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3726-5937","authenticated-orcid":false,"given":"Shaun","family":"Seaman","sequence":"additional","affiliation":[{"name":"MRC Biostatistics Unit, Cambridge, England, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paxton","family":"Bach","sequence":"additional","affiliation":[{"name":"BC Centre on Substance Use, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine, Faculty of Medicine, UBC, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehsan","family":"Karim","sequence":"additional","affiliation":[{"name":"Centre for Advancing Health Outcomes, Vancouver, British Columbia, Canada"},{"name":"School of Population and Public Health, UBC, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Platt","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Siebert","sequence":"additional","affiliation":[{"name":"Center for Health Decision Science and Departments of Epidemiology and 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 TIROL - 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