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Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study

BMJ 2020; 368 doi: (Published 31 March 2020) Cite this as: BMJ 2020;368:m772
  1. Lindsay A Pearce, project coordinator1,
  2. Jeong Eun Min, senior statistician1,
  3. Micah Piske, project coordinator1,
  4. Haoxuan Zhou, statistician1,
  5. Fahmida Homayra, statistician1,
  6. Amanda Slaunwhite, senior scientist2,
  7. Mike Irvine, postdoctoral researcher2,
  8. Gina McGowan, director of research translation3,
  9. Bohdan Nosyk, research scientist and associate professor1 4
  1. 1Health Economic Research Unit, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, V6Z 1Y6, Canada
  2. 2British Columbia Centre for Disease Control and Prevention, Vancouver, BC, V5Z 4R4, Canada
  3. 3British Columbia Ministry of Mental Health and Addictions, Victoria, BC, V8W 9P1, Canada
  4. 4Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada
  1. Correspondence to: B Nosyk bnosyk{at}
  • Accepted 18 February 2020


Objective To compare the risk of mortality among people with opioid use disorder on and off opioid agonist treatment (OAT) in a setting with a high prevalence of illicitly manufactured fentanyl and other potent synthetic opioids in the illicit drug supply.

Design Population based retrospective cohort study.

Setting Individual level linkage of five health administrative datasets capturing drug dispensations, hospital admissions, physician billing records, ambulatory care reports, and deaths in British Columbia, Canada.

Participants 55 347 people with opioid use disorder who received OAT between 1 January 1996 and 30 September 2018.

Main outcome measures All cause and cause specific crude mortality rates (per 1000 person years) to determine absolute risk of mortality and all cause age and sex standardised mortality ratios to determine relative risk of mortality compared with the general population. Mortality risk was calculated according to treatment status (on OAT, off OAT), time since starting and stopping treatment (1, 2, 3-4, 5-12, >12 weeks), and medication type (methadone, buprenorphine/naloxone). Adjusted risk ratios compared the relative risk of mortality on and off OAT over time as fentanyl became more prevalent in the illicit drug supply.

Results 7030 (12.7%) of 55 347 OAT recipients died during follow-up. The all cause standardised mortality ratio was substantially lower on OAT (4.6, 95% confidence interval 4.4 to 4.8) than off OAT (9.7, 9.5 to 10.0). In a period of increasing prevalence of fentanyl, the relative risk of mortality off OAT was 2.1 (95% confidence interval 1.8 to 2.4) times higher than on OAT before the introduction of fentanyl, increasing to 3.4 (2.8 to 4.3) at the end of the study period (65% increase in relative risk).

Conclusions Retention on OAT is associated with substantial reductions in the risk of mortality for people with opioid use disorder. The protective effect of OAT on mortality increased as fentanyl and other synthetic opioids became common in the illicit drug supply, whereas the risk of mortality remained high off OAT. As fentanyl becomes more widespread globally, these findings highlight the importance of interventions that improve retention on opioid agonist treatment and prevent recipients from stopping treatment.


  • Contributors: LAP wrote the first and subsequent drafts of the manuscript with support from JM, MP, and BN. JM did the analysis. JM, CZ, and FH cleaned the data and constructed the cohort. CZ, FH, AS, and MI provided statistical support and review. BN, JM, MP, AS, MI, and GM provided critical revisions to the manuscript. BN had the idea for the study and secured funding with the support of LAP and JM. All authors approved the final draft. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. BN is the guarantor.

  • Funding: By contribution agreement 1819-HQ-000036 from Health Canada Substance Use and Addictions Program (SUAP). The funding source was independent of the design of this study and did not have any role during its execution, analyses, data interpretation, writing, or decision to submit results. All authors had full access to the results in the study and take responsibility for the integrity of the data and accuracy of analysis.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: funding support from Health Canada SUAP; no financial relationships with any organisations that might have had an interest in the submitted work in the previous three years; no relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was mandated by the British Columbia Ministry of Mental Health and Addictions as part of the response to the provincial opioid overdose public health emergency. The Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics determined it to be exempt from research ethics board review as per Article 2.5 of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans.

  • Data sharing: Study protocol and statistical code are available from the corresponding author ( All inferences, opinions, and conclusions drawn in this manuscript do not reflect the opinions or policies of the British Columbia Ministry of Health or the data steward(s).

  • Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained.

  • Dissemination to participants and related patient and public communities: Key findings will be disseminated to local organisations of people who use drugs and people who have accessed opioid agonist treatment during an in-person meeting in Vancouver, Canada.

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