{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:49:31Z","timestamp":1788922171720,"version":"build-2803163510"},"reference-count":130,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"unspecified","delay-in-days":3,"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":[[2025,1,20]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n<jats:title>Introduction<\/jats:title>\n<jats:p>Due to inferior safety profile and higher risk of diversion than buprenorphine\/naloxone, guidelines typically recommend stringent eligibility criteria such as daily witnessed ingestion of methadone for at least 12 weeks before considering take-home doses. Recent research has focused on whether or not to initiate take-home methadone doses, often using pandemic-era data when temporary prescribing changes provided a natural experiment on the impact of access to take-home doses. However, none of these studies adequately examined the optimal timing and criteria for safely starting take-home doses to enhance treatment outcomes. To determine the optimal timing for initiating methadone take-home doses, we will compare the effects of different initiation times on time to treatment discontinuation, all-cause mortality and acute-care visits among individuals who completed methadone induction in British Columbia, Canada, from 2010 to 2022.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods and analysis<\/jats:title>\n<jats:p>We propose emulating a target trial using linked population-level health administrative data for all individuals aged 18 or older living in British Columbia, Canada, completing methadone induction between 1 January 2010 and 31 December 2022. The exposure strategies will include no take-home dosing and take-home dose initiation in \u22644, 5\u201312, 13\u201324 and 25\u201352 weeks since completed induction. The outcomes will include the time to treatment discontinuation, all-cause mortality and acute-care visits. We propose a per-protocol analysis with a clone-censor-weighting approach to address the immortal time bias implicit in the comparison of alternative take-home dose initiation times. Subgroup and sensitivity analyses, including cohort restrictions, study timeline variations, eligibility criteria modifications and outcome reclassifications, are proposed to assess the robustness of our 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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/bmjopen-2024-095198","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T18:54:13Z","timestamp":1741287253000},"page":"e095198","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative effectiveness of methadone take-home dose initiation in British Columbia, Canada: protocol for a population-based retrospective cohort study using target trial guidelines"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-863X","authenticated-orcid":false,"given":"Md. Belal","family":"Hossain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda Carolina","family":"Guerra-Alejos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Kurz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ehsanul","family":"Karim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3726-5937","authenticated-orcid":false,"given":"Shaun","family":"Seaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paxton","family":"Bach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Platt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2375-5006","authenticated-orcid":false,"given":"Paul","family":"Gustafson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bruneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"McCandless","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Soc\u00edas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-3718","authenticated-orcid":false,"given":"Bohdan","family":"Nosyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"2025040100160893000_15.3.e095198.1","doi-asserted-by":"publisher","DOI":"10.24095\/hpcdp.38.6.02"},{"key":"2025040100160893000_15.3.e095198.2","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/1556-4029.14712","article-title":"Fentanyl-related substance scheduling as an effective drug control strategy","volume":"66","author":"Weedn","year":"2021","journal-title":"J Forensic Sci"},{"key":"2025040100160893000_15.3.e095198.3","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S2215-0366(18)30337-7","article-title":"The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"5","author":"Degenhardt","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"2025040100160893000_15.3.e095198.4","unstructured":"World Health Organization . Opioid overdose. 2023. Available: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/opioid-overdose [Accessed 15 Jan 2024]."},{"key":"2025040100160893000_15.3.e095198.5","unstructured":"Statista . Distribution of deaths from opioid overdose in canada from 2016 to 2023, by age. 2024. Available: https:\/\/www.statista.com\/statistics\/1299434\/opioid-overdose-deaths-distribution-canada-by-age\/#:~:text=In [Accessed 1 Oct 2024]."},{"key":"2025040100160893000_15.3.e095198.6","unstructured":"National Center for Health Statistics . U.su.s. overdose deaths decrease in 2023, first time since 2018. 2024. Available: https:\/\/www.cdc.gov\/nchs\/pressroom\/nchs_press_releases\/2024\/20240515.htm#:~:text=The [Accessed 1 Oct 2024]."},{"key":"2025040100160893000_15.3.e095198.7","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.j1550","article-title":"Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies","volume":"357","author":"Sordo","year":"2017","journal-title":"BMJ"},{"key":"2025040100160893000_15.3.e095198.8","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1037\/a0037550","article-title":"A naturalistic comparison of the effectiveness of methadone and two sublingual formulations of buprenorphine on maintenance treatment outcomes: findings from a retrospective multisite study","volume":"22","author":"Proctor","year":"2014","journal-title":"Exp Clin Psychopharmacol"},{"key":"2025040100160893000_15.3.e095198.9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0740-5472(03)00024-2","article-title":"Methadone versus buprenorphine maintenance for the treatment of heroin-dependent outpatients","volume":"24","author":"Ahmadi","year":"2003","journal-title":"J Subst Abuse Treat"},{"key":"2025040100160893000_15.3.e095198.10","article-title":"Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence","volume":"2014","author":"Mattick","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2025040100160893000_15.3.e095198.11","doi-asserted-by":"publisher","DOI":"10.1016\/0376-8716(95)01186-2"},{"key":"2025040100160893000_15.3.e095198.12","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.drugalcdep.2018.04.026","article-title":"Trends in engagement in the cascade of care for opioid use disorder, Vancouver, Canada, 2006-2016","volume":"189","author":"Soc\u00edas","year":"2018","journal-title":"Drug Alcohol Depend"},{"key":"2025040100160893000_15.3.e095198.13","unstructured":"BC Coroners Service . Unregulated drug deaths- summary. 2024. Available: https:\/\/www2.gov.bc.ca\/assets\/gov\/birth-adoption-death-marriage-and-divorce\/deaths\/coroners-service\/statistical\/augsept2024_2_unregulated_drug_pdf_of_dashboard.pdf [Accessed 26 Feb 2025]."},{"key":"2025040100160893000_15.3.e095198.14","doi-asserted-by":"publisher","DOI":"10.1186\/s12954-021-00535-y"},{"key":"2025040100160893000_15.3.e095198.15","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13011-023-00564-9","article-title":"The impact of relaxing restrictions on take-home doses during the COVID-19 pandemic on program effectiveness and client experiences in opioid agonist treatment: a mixed methods systematic review","volume":"18","author":"Adams","year":"2023","journal-title":"Subst Abuse Treat Prev Policy"},{"key":"2025040100160893000_15.3.e095198.16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.1271"},{"key":"2025040100160893000_15.3.e095198.17","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.170958"},{"key":"2025040100160893000_15.3.e095198.18","unstructured":"CRISM National Guideline Review Committee . CRISM national guidelines for the clinical management of opioid use disorder. 2018. Available: https:\/\/crism.ca\/projects\/opioid-guideline\/"},{"key":"2025040100160893000_15.3.e095198.19","unstructured":"British columbia centre on substance use, bc ministry of health, bc ministry of mental health and addictions . A guideline for the clinical management of opioid use disorder. 2023. Available: https:\/\/www.bccsu.ca\/opioid-use-disorder\/"},{"key":"2025040100160893000_15.3.e095198.20","unstructured":"SAMHSA Center for Substance Abuse Treatment . TIP 43: medication-assisted treatment for opioid addiction in opioid treatment programs. Available: https:\/\/www.hrsa.gov\/behavioral-health\/tip-43-medication-assisted-treatment-opioid-addiction-opioid-treatment-programs [Accessed 27 Mar 2024]."},{"key":"2025040100160893000_15.3.e095198.21","unstructured":"Government of British Columbia . A guideline for the clinical management of opioid use disorder. 2017."},{"key":"2025040100160893000_15.3.e095198.22","unstructured":"Government of British Columbia . Methadone maintenance payment program. 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/practitioner-professional-resources\/pharmacare\/pharmacare-publications\/pharmacare-policy-manual-2012\/pharmacyfees-subsidies-providerpayment\/methadone-maintenance-payment-program [Accessed 15 May 2024]."},{"key":"2025040100160893000_15.3.e095198.23","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/hec.4255","article-title":"The effect of British Columbia\u2019s Pharmacare coverage expansion for opioid agonist treatment","volume":"30","author":"Hongdilokkul","year":"2021","journal-title":"Health Econ"},{"key":"2025040100160893000_15.3.e095198.24","unstructured":"Government of British Columbia . Drug coverage for opioid use disorder. 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/health-drug-coverage\/pharmacare-for-bc-residents\/what-we-cover\/drug-coverage-opioid-use-disorder [Accessed 27 Mar 2024]."},{"key":"2025040100160893000_15.3.e095198.25","unstructured":"Government of British Columbia . OAT PINs and DINs. 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/practitioner-professional-resources\/pharmacare\/pharmacies\/product-identification-numbers\/oat-pins-and-dins [Accessed 27 Mar 2024]."},{"key":"2025040100160893000_15.3.e095198.26","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1111\/add.16160","article-title":"Incremental expenditures attributable to daily dispensation and witnessed ingestion for opioid agonist treatment in British Columbia: 2014-20","volume":"118","author":"Nosyk","year":"2023","journal-title":"Addiction"},{"key":"2025040100160893000_15.3.e095198.27","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1300\/J069v25n03_02","article-title":"Methadone induction doses: are our current practices safe?","volume":"25","author":"Srivastava","year":"2006","journal-title":"J Addict Dis"},{"key":"2025040100160893000_15.3.e095198.28","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.jpsychires.2013.07.001","article-title":"Higher methadone doses are associated with lower mortality in patients of opioid dependence in Taiwan","volume":"47","author":"Liao","year":"2013","journal-title":"J Psychiatr Res"},{"key":"2025040100160893000_15.3.e095198.29","unstructured":"Lam V , Latreille S , McLeod A , et al . A new framework for methadone carries: a person-centered evidence-informed approach to methadone takehome \u201ccarry\u201d dosing. 2023 Available: https:\/\/www.metaphi.ca\/wp-content\/uploads\/CarryPrinciples.pdf"},{"key":"2025040100160893000_15.3.e095198.30","unstructured":"Alberta College of Pharmacy . Opioid agonist therapy (oat) guidelines medicationassisted treatment for opioid use disorder: guidelines for pharmacists and pharmacy technicians. 2022. Available: https:\/\/abpharmacy.ca\/wp-content\/uploads\/Guidelines_OAT.pdf"},{"key":"2025040100160893000_15.3.e095198.31","unstructured":"Saskatchewan College of Pharmacy Professionals . Opioid agonist therapy (oat) standards. 2020. Available: https:\/\/www.saskpharm.ca\/document\/5871\/REF_OAT_Standards.pdf"},{"key":"2025040100160893000_15.3.e095198.32","unstructured":"The College of Physicians & Surgeons of Manitoba . Manitoba methadone & buprenorphine maintenance recommended practice. 2024. Available: https:\/\/www.cpsm.mb.ca\/prescribing-practices-program\/manitoba-buprenorphine-naloxone-recommended-practice-manual"},{"key":"2025040100160893000_15.3.e095198.33","unstructured":"The College of Physicians & Surgeons of Manitoba . Manitoba opioid agonist therapy recommended practice: recommendations for the in-hospital care of individuals with opioid use disorder. 2023. Available: https:\/\/cpsm.mb.ca\/prescribing-practices-program\/manitoba-buprenorphine-naloxone-recommended-practice-manual"},{"key":"2025040100160893000_15.3.e095198.34","unstructured":"College of Physicians and Surgeons of Ontario. Methadone Maintenance Treatment Program Standards and Clinical Guidelines 2011. doi:10.13140\/2.1.4346.9128"},{"key":"2025040100160893000_15.3.e095198.35","unstructured":"The College of Physicians and Surgeons of Prince Edward Island . Policy on prescribing methadone maintenance treatment for opioid dependency. 2012. Available: https:\/\/www.cpspei.ca\/wp-content\/uploads\/2012\/12\/Policy-on-METHADONE-Maintenace-Treatment-for-Opioid-Dependency-Nov-2012.pdf"},{"key":"2025040100160893000_15.3.e095198.36","unstructured":"New Brunswick College of Pharmacists . Methadone maintenance treatment policies and procedures. 2018. Available: https:\/\/nbpharmacists.ca\/wp-content\/uploads\/2022\/07\/OAT-PracticeDirectiveDocumentationTemplatesJuly2022EN.pdf"},{"key":"2025040100160893000_15.3.e095198.37","unstructured":"College of physicians and surgeons of nova scotia . In: CPSNS methadone maintenance treatment handbook. 2012. Available: https:\/\/drugslibrary.wordpress.stir.ac.uk\/files\/2017\/07\/guideline-methadone-maintenance.pdf"},{"key":"2025040100160893000_15.3.e095198.38","unstructured":"College of Physicians and Surgeons of Newfoundland and Labrador . Practice guideline: opioid prescribing for opioid use disorder. 2022. Available: https:\/\/cpsnl.ca\/wp-content\/uploads\/Standards-and-Guidelines\/Opioid-Prescribing-for-Opioid-Use-Disorder.pdf"},{"key":"2025040100160893000_15.3.e095198.39","unstructured":"Substance abuse and mental health services administration . In: Medications for Opioid Use 30 Disorder: For Healthcare and Addiction Professionals, Policymakers, Patients, and Families. 2021. Available: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK535268\/"},{"key":"2025040100160893000_15.3.e095198.40","unstructured":"Centre for Addiction and Mental Health . Opioid agonist therapy: a synthesis of canadian guidelines for treating opioid use disorder. 2021. Available: http:\/\/www.camh.ca\/"},{"key":"2025040100160893000_15.3.e095198.41","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000668"},{"key":"2025040100160893000_15.3.e095198.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2022.109703"},{"key":"2025040100160893000_15.3.e095198.43","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1080\/00952990.2023.2222336","article-title":"Opioid use and COVID-19: a secondary analysis of the impact of relaxation of methadone take-home dosing guidelines on use of illicit opioids","volume":"49","author":"Panwala","year":"2023","journal-title":"Am J Drug Alcohol Abuse"},{"key":"2025040100160893000_15.3.e095198.44","doi-asserted-by":"crossref","first-page":"209086","DOI":"10.1016\/j.josat.2023.209086","article-title":"Changes to methadone maintenance therapy in the United States, Canada, and Australia during the COVID-19 pandemic: A narrative review","volume":"152","author":"Panwala","year":"2023","journal-title":"J Subst Use Addict Treat"},{"key":"2025040100160893000_15.3.e095198.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugpo.2022.103644"},{"key":"2025040100160893000_15.3.e095198.46","doi-asserted-by":"publisher","DOI":"10.1081\/JA-120017386"},{"key":"2025040100160893000_15.3.e095198.47","doi-asserted-by":"crossref","first-page":"S149","DOI":"10.1097\/00126334-200212153-00013","article-title":"Nonadherence Among HIV-Infected Injecting Drug Users: The Impact of Social Instability","volume":"31","author":"Bouhnik","year":"2002","journal-title":"JAIDS Journal of Acquired Immune Deficiency Syndromes"},{"key":"2025040100160893000_15.3.e095198.48","first-page":"23333928211048640","article-title":"Social Stability and Unmet Health Care Needs in a Community-Based Sample of Women Who Use Drugs","volume":"8","author":"Akr\u00e9","year":"2021","journal-title":"Health Serv Res Manag Epidemiol"},{"key":"2025040100160893000_15.3.e095198.49","unstructured":"Substance Abuse and Mental Health Services (SAMHSA) . Opioid treatment program (otp) guidance. 2020. Available: https:\/\/www.samhsa.gov\/sites\/default\/files\/otp-guidance-20200316.pdf [Accessed 15 Jan 2024]."},{"key":"2025040100160893000_15.3.e095198.50","doi-asserted-by":"crossref","first-page":"108552","DOI":"10.1016\/j.jsat.2021.108552","article-title":"Changes in methadone take-home dosing before and after COVID-19","volume":"133","author":"Amram","year":"2022","journal-title":"J Subst Abuse Treat"},{"key":"2025040100160893000_15.3.e095198.51","unstructured":"Ling W , Stephenson D , Vasti E . Guidelines for physicians working in california opioid treatment programs. 2019. Available: https:\/\/csam-asam.org\/wp-content\/uploads\/csam-guidelines.pdf"},{"key":"2025040100160893000_15.3.e095198.52","unstructured":"Gowing L , Ali R , Dunlop A , et al . National guidelines for medicationassisted treatment of opioid dependence. 2014. Available: https:\/\/www.health.gov.au\/sites\/default\/files\/national-guidelines-for-medication-assisted-treatment-of-opioid-dependence.pdf"},{"key":"2025040100160893000_15.3.e095198.53","unstructured":"Western Australian Drug and Alcohol Office . Western australian community program for 31 opioid pharmacotherapy (cpop): clinical policies and procedures for the use of methadone and buprenorphine in the treatment of opioid dependence. 2014. Available: https:\/\/www.mhc.wa.gov.au\/media\/1614\/wa-clinical-policies-and-procedures-for-the-use-of-methadone.pdf"},{"key":"2025040100160893000_15.3.e095198.54","unstructured":"New South Wales Ministry of Health . NSW clinical guidelines: treatment of opioid dependence. 2018. Available: https:\/\/www.health.nsw.gov.au\/aod\/Pages\/nsw-clinical-guidelines-opioid.aspx"},{"key":"2025040100160893000_15.3.e095198.55","unstructured":"New Zealand Ministry of Health . New zealand practice guidelines for opioid substitution treatment. 2014. Available: https:\/\/www.health.govt.nz\/publication\/new-zealand-practice-guidelines-opioid-substitution-treatment-2014"},{"key":"2025040100160893000_15.3.e095198.56","unstructured":"Independent Expert Working Group . Drug misuse and dependence: uk guidelines on clinical management. 2017. Available: https:\/\/assets.publishing.service.gov.uk\/media\/5a821e3340f0b62305b92945\/clinical_guidelines_2017.pdf"},{"key":"2025040100160893000_15.3.e095198.57","unstructured":"National Institute for Health and Care Excellence (NICE) . Opioid dependence. 2022. Available: https:\/\/cks.nice.org.uk\/topics\/opioid-dependence\/"},{"key":"2025040100160893000_15.3.e095198.58","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/ajad.13439","article-title":"Associations of methadone and buprenorphine-naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription-type opioid use disorders: Exploratory analyses of the OPTIMA study","volume":"32","author":"Bakouni","year":"2023","journal-title":"Am J Addict"},{"key":"2025040100160893000_15.3.e095198.59","doi-asserted-by":"publisher","DOI":"10.1111\/add.15087"},{"key":"2025040100160893000_15.3.e095198.60","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s40263-018-0560-2","article-title":"Buprenorphine\/Naloxone (Zubsolv\u00ae): A Review in Opioid Dependence","volume":"32","author":"Heo","year":"2018","journal-title":"CNS Drugs"},{"key":"2025040100160893000_15.3.e095198.61","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000045"},{"key":"2025040100160893000_15.3.e095198.62","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1176\/appi.ajp.20220687","article-title":"Flexible Buprenorphine\/Naloxone Treatment Models: Safe and Effective in Reducing Opioid Use Among Persons With Prescription Opioid Use Disorder","volume":"179","author":"Saunders","year":"2022","journal-title":"Am J Psychiatry"},{"key":"2025040100160893000_15.3.e095198.63","doi-asserted-by":"publisher","DOI":"10.1007\/s002130051096"},{"key":"2025040100160893000_15.3.e095198.64","unstructured":"Lam V , Sankey C , Wyman J , et al . COVID-19: opioid agonist treatment guidance. 2020. Available: https:\/\/www.camh.ca\/-\/media\/files\/covid-19-modifications-to-opioid-agonist-treatment-delivery-pdf.pdf"},{"key":"2025040100160893000_15.3.e095198.65","unstructured":"Lintzeris N , Hayes V , Arunogiri S . Interim guidance for the delivery of medication assisted treatment of opioid dependence in response to covid-19: a national response. 2020. Available: https:\/\/www.racp.edu.au\/docs\/default-source\/news-and-events\/covid-19\/interim-guidance-delivery-of-medication-assisted-treatment-of-opiod-dependence-covid-19.pdf?sfvrsn=e36eeb1a_4"},{"key":"2025040100160893000_15.3.e095198.66","unstructured":"Department of Health and Social Care . COVID-19: guidance for commissioners and providers of services for people who use drugs or alcohol. 2020. Available: https:\/\/www.gov.uk\/government\/publications\/covid-19-guidance-for-commissioners-and-providers-of-services-for-people-who-use-drugs-or-alcohol\/covid-19-guidance-for-commissioners-and-providers-of-services-for-people-who-use-drugs-or-alcohol"},{"key":"2025040100160893000_15.3.e095198.67","doi-asserted-by":"crossref","DOI":"10.1016\/j.psychres.2020.113047","article-title":"COVID19 pandemic and people with opioid use disorder: innovation to reduce risk","volume":"289","author":"Vecchio","year":"2020","journal-title":"Psychiatry Res"},{"key":"2025040100160893000_15.3.e095198.68","unstructured":"Departament de Salut . Coronavirus sars-cov-2: recomanacions per reduir el risc de contagi de la covid-19 per a centres d\u2019atenci\u00f3 i seguiment de les drogodepend\u00e8ncies (cas) [fullet]. 2020. Available: https:\/\/scientiasalut.gencat.cat\/handle\/11351\/4799"},{"key":"2025040100160893000_15.3.e095198.69","unstructured":"Substance Abuse and Mental Health Services Administration . Methadone take-home flexibilities extension guidance. 2024. Available: https:\/\/www.samhsa.gov\/medications-substance-use-disorders\/statutes-regulations-guidelines\/methadone-guidance [Accessed 20 Dec 2024]."},{"key":"2025040100160893000_15.3.e095198.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsat.2021.108449"},{"key":"2025040100160893000_15.3.e095198.71","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1001\/jamapsychiatry.2022.1776","article-title":"Methadone-Involved Overdose Deaths in the US Before and After Federal Policy Changes Expanding Take-Home Methadone Doses From Opioid Treatment Programs","volume":"79","author":"Jones","year":"2022","journal-title":"JAMA Psychiatry"},{"key":"2025040100160893000_15.3.e095198.72","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/ADM.0000000000000812","article-title":"Reduction in Oregon\u2019s Medication Dosing Visits After the SARS-CoV-2 Relaxation of Restrictions on Take-home Medication","volume":"15","author":"McIlveen","year":"2021","journal-title":"J Addict Med"},{"key":"2025040100160893000_15.3.e095198.73","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2021.1979991"},{"key":"2025040100160893000_15.3.e095198.74","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1465-3362.2011.00394.x","article-title":"A pilot randomised controlled trial of brief versus twice weekly versus standard supervised consumption in patients on opiate maintenance treatment","volume":"31","author":"Holland","year":"2012","journal-title":"Drug Alcohol Rev"},{"key":"2025040100160893000_15.3.e095198.75","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/ADM.0b013e3182584772","article-title":"Methadone dose, take home status, and hospital admission among methadone maintenance patients","volume":"6","author":"Walley","year":"2012","journal-title":"J Addict Med"},{"key":"2025040100160893000_15.3.e095198.76","doi-asserted-by":"crossref","first-page":"S143","DOI":"10.2105\/AJPH.2022.306806","article-title":"Federal and State Regulatory Changes to Methadone Take-Home Doses: Impact of Sociostructural Factors","volume":"112","author":"Wyatt","year":"2022","journal-title":"Am J Public Health"},{"key":"2025040100160893000_15.3.e095198.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsat.2021.108276"},{"key":"2025040100160893000_15.3.e095198.78","doi-asserted-by":"crossref","first-page":"109100","DOI":"10.1016\/j.drugalcdep.2021.109100","article-title":"Treatment provider perceptions of take-home methadone regulation before and during COVID-19","volume":"228","author":"Madden","year":"2021","journal-title":"Drug Alcohol Depend"},{"key":"2025040100160893000_15.3.e095198.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsat.2021.108288"},{"key":"2025040100160893000_15.3.e095198.80","doi-asserted-by":"publisher","DOI":"10.1016\/j.socscimed.2021.113986"},{"key":"2025040100160893000_15.3.e095198.81","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2023.111579"},{"key":"2025040100160893000_15.3.e095198.82","unstructured":"British Columbia Ministry of Health [creator] . Client roster. British Columbia Ministry of health [publisher]. Data Extract. MOH (2024); 2024. Available: http:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.83","unstructured":"British Columbia Ministry of Health [creator] . PharmaNet. British Columbia Ministry of Health [publisher]. Data Extract. MOH (2024); 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.84","unstructured":"British Columbia Ministry of Health [creator] . Medical services plan (msp) payment information file. British Columbia Ministry of Health [publisher]. Data Extract. MOH (2024); 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.85","unstructured":"Canadian Institute of Health Information [creator] . Discharge abstract database (hospital separations). British Columbia Ministry of Health [publisher]. Data Extract. MOH (2024); 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.86","unstructured":"British Columbia Ministry of Health [creator] . National ambulatory care reporting system (nacrs). British Columbia Ministry of health [publisher]. Data Extract. MOH; 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.87","unstructured":"Ministry of Public Safety and Solicitor General (PSSG) [creator] . BC corrections dataset. british columbia ministry of health [publisher]. Data Extract. MOH (2024); 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.88","unstructured":"Perinatal Services BC [creator] . British columbia perinatal data registry. years provided: 2000 to 2022. British Columbia Ministry of Health [publisher]. Data Extract. MOH (2024); 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.89","unstructured":"British Columbia Ministry of Social Development and Poverty Reduction [creator] . Social development and poverty reduction database (sdpr). british columbia ministry of health [publisher]. Data Extract. MOH (2024); 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.90","unstructured":"British Columbia Ministry of Health . Vital statistics deaths. British Columbia Ministry of Health [publisher]. Data Extract. MOH; 2024. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/conducting-health-research-evaluation\/data-access-health-data-central"},{"key":"2025040100160893000_15.3.e095198.91","unstructured":"Government of British Columbia . Personal health identification. 2023. Available: https:\/\/www2.gov.bc.ca\/gov\/content\/health\/health-drug-coverage\/msp\/bc-residents\/personal-health-identification [Accessed 10 Oct 2024]."},{"key":"2025040100160893000_15.3.e095198.92","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2019-036102","article-title":"Comparative effectiveness of buprenorphine-naloxone versus methadone for treatment of opioid use disorder: a population-based observational study protocol in British Columbia, Canada","volume":"10","author":"Piske","year":"2020","journal-title":"BMJ Open"},{"key":"2025040100160893000_15.3.e095198.93","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2022-068729","article-title":"Comparative effectiveness of urine drug screening strategies alongside opioid agonist treatment in British Columbia, Canada: a population-based observational study protocol","volume":"13","author":"Guerra-Alejos","year":"2023","journal-title":"BMJ Open"},{"key":"2025040100160893000_15.3.e095198.94","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13012-023-01331-x","article-title":"Influence of physician networks on the implementation of pharmaceutical alternatives to a toxic drug supply in British Columbia","volume":"19","author":"Kurz","year":"2024","journal-title":"Implement Sci"},{"key":"2025040100160893000_15.3.e095198.95","doi-asserted-by":"crossref","first-page":"108647","DOI":"10.1016\/j.jsat.2021.108647","article-title":"Assessing the determinants of completing OAT induction and long-term retention: A population-based study in British Columbia, Canada","volume":"133","author":"Kurz","year":"2022","journal-title":"J Subst Abuse Treat"},{"key":"2025040100160893000_15.3.e095198.96","doi-asserted-by":"publisher","DOI":"10.1300\/J069v18n04_05"},{"key":"2025040100160893000_15.3.e095198.97","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000323"},{"key":"2025040100160893000_15.3.e095198.98","article-title":"Methadone for cancer pain","volume":"2","author":"Nicholson","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"2025040100160893000_15.3.e095198.99","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jpainsymman.2018.12.001","article-title":"Safe and Appropriate Use of Methadone in Hospice and Palliative Care: Expert Consensus White Paper","volume":"57","author":"McPherson","year":"2019","journal-title":"J Pain Symptom Manage"},{"key":"2025040100160893000_15.3.e095198.100","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwi307"},{"key":"2025040100160893000_15.3.e095198.101","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1007\/s00125-017-4518-6","article-title":"Promises and pitfalls of electronic health record analysis","volume":"61","author":"Farmer","year":"2018","journal-title":"Diabetologia"},{"key":"2025040100160893000_15.3.e095198.102","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2016.07.017"},{"key":"2025040100160893000_15.3.e095198.103","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3437"},{"key":"2025040100160893000_15.3.e095198.104","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2016.04.014"},{"key":"2025040100160893000_15.3.e095198.105","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1093\/ije\/dyaa057","article-title":"Reflection on modern methods: trial emulation in the presence of immortal-time bias. Assessing the benefit of major surgery for elderly lung cancer patients using observational data","volume":"49","author":"Maringe","year":"2020","journal-title":"Int J Epidemiol"},{"key":"2025040100160893000_15.3.e095198.106","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv254"},{"key":"2025040100160893000_15.3.e095198.107","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780091214"},{"key":"2025040100160893000_15.3.e095198.108","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1097\/00001648-200009000-00011","article-title":"Marginal Structural Models and Causal Inference in Epidemiology","volume":"11","author":"Robins","year":"2000","journal-title":"Epidemiology (Sunnyvale)"},{"key":"2025040100160893000_15.3.e095198.109","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1177\/26320843221085649","article-title":"Considerations for choosing an imputation method for addressing sparse measurement issues dictated by the study design - An illustration from per-protocol analysis in pragmatic trials","volume":"3","author":"Karim","year":"2022","journal-title":"Research Methods in Medicine & Health Sciences"},{"key":"2025040100160893000_15.3.e095198.110","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv152"},{"key":"2025040100160893000_15.3.e095198.111","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s13063-018-2519-5","article-title":"Improved adherence adjustment in the Coronary Drug Project","volume":"19","author":"Murray","year":"2018","journal-title":"Trials"},{"key":"2025040100160893000_15.3.e095198.112","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwn164"},{"key":"2025040100160893000_15.3.e095198.113","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1198\/jbes.2010.07136","article-title":"Robust Inference With Multiway Clustering","volume":"29","author":"Cameron","year":"2011","journal-title":"Journal of Business & Economic Statistics"},{"key":"2025040100160893000_15.3.e095198.114","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu122"},{"key":"2025040100160893000_15.3.e095198.115","doi-asserted-by":"publisher","DOI":"10.1136\/jech.2004.029496"},{"key":"2025040100160893000_15.3.e095198.116","doi-asserted-by":"publisher","DOI":"10.1177\/0962280210386207"},{"key":"2025040100160893000_15.3.e095198.117","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4048"},{"key":"2025040100160893000_15.3.e095198.118","doi-asserted-by":"crossref","unstructured":"Williams A , Krawczyk N , Hu M-C , et al . Retention and critical outcomes among new methadone maintenance patients following extended take-home reforms. SSRN [Preprint] 2023. doi:10.2139\/ssrn.4439150","DOI":"10.2139\/ssrn.4439150"},{"key":"2025040100160893000_15.3.e095198.119","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.11389","article-title":"Opioid Coprescription Through Risk Mitigation Guidance and Opioid Agonist Treatment Receipt","volume":"7","author":"Min","year":"2024","journal-title":"JAMA Netw Open"},{"key":"2025040100160893000_15.3.e095198.120","unstructured":"Provincial Health Services Authority . Unregulated drug poisoning emergency dashboard. 2025. Available: http:\/\/www.bccdc.ca\/health-professionals\/data-reports\/substance-use-harm-reduction-dashboard [Accessed 9 Jan 2025]."},{"key":"2025040100160893000_15.3.e095198.121","doi-asserted-by":"crossref","unstructured":"Robins JM . Analytic methods for estimating HIV-treatment and cofactor effects. Methodol issues AIDS Behav Res. Published Online 1993;213\u201388. doi:10.1007\/0-306-47137-X_12","DOI":"10.1007\/0-306-47137-X_12"},{"key":"2025040100160893000_15.3.e095198.122","doi-asserted-by":"crossref","DOI":"10.1186\/s12874-021-01449-w","article-title":"Instrumental variable estimation for a time-varying treatment and a time-to-event outcome via structural nested cumulative failure time models","volume":"21","author":"Shi","year":"2021","journal-title":"BMC Med Res Methodol"},{"key":"2025040100160893000_15.3.e095198.123","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2009.02627.x"},{"key":"2025040100160893000_15.3.e095198.124","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsat.2017.07.001"},{"key":"2025040100160893000_15.3.e095198.125","doi-asserted-by":"crossref","unstructured":"Henry-Edwards S , Gowing L , White J , et al . Clinical guidelines and procedures for the use of methadone in the maintenance treatment of opioid dependence. 2003.","DOI":"10.1037\/e677012010-001"},{"key":"2025040100160893000_15.3.e095198.126","doi-asserted-by":"crossref","first-page":"7668","DOI":"10.1080\/03610918.2016.1248574","article-title":"On the application of statistical learning approaches to construct inverse probability weights in marginal structural Cox models: Hedging against weight-model misspecification","volume":"46","author":"Karim","year":"2017","journal-title":"Communications in Statistics - Simulation and Computation"},{"key":"2025040100160893000_15.3.e095198.127","unstructured":"Canadian institutes of health research, natural sciences and engineering research council of canada, social sciences and research humanities council . Tri-council policy statement: ethical conduct for research involving humans. 2018."},{"key":"2025040100160893000_15.3.e095198.128","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001885","article-title":"The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement","volume":"12","author":"Benchimol","year":"2015","journal-title":"PLoS Med"},{"key":"2025040100160893000_15.3.e095198.129","unstructured":"World Health Organization . WHO model lists of essential medicines. 2023. Available: https:\/\/www.who.int\/groups\/expert-committee-on-selection-and-use-of-essential-medicines\/essential-medicines-lists [Accessed 30 Jan 2024]."},{"key":"2025040100160893000_15.3.e095198.130","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2006.01714.x"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-095198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T12:31:08Z","timestamp":1743597068000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-095198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":130,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,5]]},"published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1136\/bmjopen-2024-095198"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-095198","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]}}}