A1.1 Funding
Guideline development activities were entirely supported by funding provided by the BC Ministry of Mental Health and Addictions and the BC Ministry of Health to the BCCSU. No support was received from the pharmaceutical industry or associated stakeholders for guideline development.
A1.2 Committee Membership
The first edition of the BCCSU Guideline for the Clinical Management of Opioid Use Disorder (2017) was developed by an interdisciplinary committee of 28 experts with representation from each health authority, the Ministry of Health, BC Corrections Services, and the First Nations Health Authority. In keeping with the BCCSU’s commitment to regular review and update of clinical guidelines, the OUD guideline committee was reconvened in 2019 in order to begin the update process.
In 2020, the work of the committee was paused due to the COVID-19 pandemic, which shifted the BCCSU’s focus to addressing emergent needs related to the dual public health emergencies. The guideline update work resumed in May 2022. At this point, the committee list was revised to ensure member availability and improve geographic and disciplinary representation. Ultimately, the re-assembled OUD committee responsible for the development of the second edition of the guideline consisted of 31 members (5 existing members and 26 new members).
This committee includes representation from each regional Health Authority in BC, the Provincial Health Services Authority, the First Nations Health Authority, BC Ministry of Health, and Ministry of Mental Health and Addictions. The committee was composed of experts in the fields of substance use care, psychiatry, family practice, nursing, pharmacy, recovery-oriented systems of care, and health care administration and policy, as well as people and family members with lived experience.
Conflict of interest policy
In line with Guidelines International Network’s Principles for Disclosure of Interests and Management of Conflicts,463 committee members were required to disclose all sources and amounts of direct and indirect remuneration received in the past five years from industry, for-profit enterprises, and other entities (i.e., direct financial conflicts) that could introduce real, potential, or perceived risk of bias. In addition, committee members were asked to report possible indirect conflicts of interest, such as academic advancement, clinical/professional revenue, and public standing that could potentially influence interpretation of evidence and formulation of the strategies contained in this guidance.
Conflict of interest summary
In terms of indirect sources of potential interest or bias, one committee member is involved in research evaluating opioid agonist treatment. Of the 31 individuals on the committee, 24 members disclosed expertise and/or experience with the topics of the guideline. This pertained to clinical practice (e.g., addiction medicine clinician or service provider), personal experience, academic publications, and public advocacy. In addition, 4 committee members reported that their clinical revenue could potentially be influenced by the guidance in this document. Upon review, of those who disclosed potential indirect conflicts of interest or bias, none were deemed to be of sufficient relevance or weight to warrant exclusion from the committee.
A1.3 Guideline Development Process
The OUD guideline committee had its initial meeting for the development of the OUD guideline’s second edition in November 2019. In this meeting, the outline, scope, and planned major revisions of the guideline were provisionally approved by committee consensus with reference to the results of a preliminary literature search conducted earlier in that year. Subsequently, 3 working groups were formed to develop updated clinical guidance for:
- Initiation, titration, and dosing of OAT medications
- Continuing care considerations for patients on OAT
- Take-home dosing considerations
Decisions made in the initial committee meeting and subsequent email communications informed literature searches and reviews and the drafting process. However, this work was put on hold in March 2020 due to the COVID-19 pandemic, before the committee was able to review the first draft.
Upon resumption of the OUD guideline development work in 2022, an updated systematic literature search was conducted by an information specialist in consultation with committee co-chairs and medical writers, and the draft guideline was updated accordingly.
Between September 2022 and January 2023, each working group conferred over email and, in the case of working groups 1 and 3, video conference to discuss and approve draft guideline contents and recommendations. During this process, targeted literature searches and reviews were conducted to address specific working group concerns. The full draft of the guideline was reviewed in the course of two revision rounds and a full committee meeting to reach consensus in January 2023.
Consistent with best practices for guideline development, the AGREE-II instrument464 was used throughout development and revision phases to ensure the guideline met international standards for transparency, high quality, and methodological rigour.
A1.3.i Literature Search Strategy
The second edition of the OUD guideline expanded on the structured literature search that was conducted for the first edition in 2016. For the development of the present edition, updated systematic literature searches were performed in December 2019 and May 2022.
Using a search strategy approved by committee co-chairs, an information specialist performed the literature searches for the following databases: Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials via Ovid; CINAHL and PsycINFO via EbscoHost. Search date limits started at 2016 to identify studies published after the literature search conducted for the previous edition of the guideline.
Studies were excluded if they did not meet inclusion criteria established a priori or if they were already included in high-quality systematic reviews and meta-analyses. There was no search of unpublished research. Additional details of the search strategy are provided below.
In December 2022, a supplementary targeted search of peer-reviewed and grey literature was performed by an information specialist to address specific questions posed by working groups concerning starting OAT doses, strategies to address missed doses, and developments in take home dosing policies and protocols.
A1.3.ii Study Selection and Critical Appraisal
Two medical writers independently screened and identified eligible studies. Discordance between reviewers on inclusion or exclusion of individual studies was resolved through discussion with no need for arbitration. A PRISMA flowchart is included below. One reviewer used validated assessment tools (e.g., AMSTAR-2, Cochrane Risk of Bias Tool, Downs and Black checklist) to evaluate study quality. The writers then updated the evidence summaries for review by each of the working groups.
PRISMA Flow Chart— May 2022 Literature Search
A1.3.iii Development and Approval of Recommendations
After reviewing and providing feedback on the evidence summaries, each working group determined through consensus whether the recommendations should be accepted without modification, adapted, or removed. For adaptations to existing recommendations or the development of new recommendations, the working groups used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool1 to score recommendations.
Grade quality of evidence
Initial estimates of quality are based on a traditional hierarchy of evidence, whereby meta-analyses of randomized clinical trials are assigned the highest score, followed by individual clinical trials, quasi- or non-randomized trials, observational studies and reports, and expert opinion, which is assigned the lowest score. Factors that lowered confidence in the estimated effect of an intervention included risk of bias, inconsistency across the RCTs, indirectness, and publication bias; factors that increased confidence include large effect sizes and an observed dose-response effect. The final quality ratings are reflective of the estimated effect of an intervention as reported in the literature with consideration of biases and limitations of the evidence base as identified by the committee.
Table 3. GRADE Quality of Evidence
|
Quality of Evidence |
Definition |
| High | Further research is very unlikely to change our confidence in the estimate of effect |
| Moderate | Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate |
| Low | Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate |
| Very low | Any estimate of effect is very uncertain |
Strength of recommendation
To determine strength of recommendations, the GRADE system takes into account the quality of evidence as well as additional factors, such as clinician, patient, and policy maker’s values and preferences, costs and cost-effectiveness, risk-benefit ratios, and feasibility.466
Table 4. GRADE Strength of Recommendation
|
Strength of Recommendation |
Definition |
| Strong | Implies that all patients in a specific situation would want the recommended course of action and that only a small proportion of the genera patient population would not. |
| Weak (Conditional) |
Implies that most patients in specific situations would want the recommended course of action but many would not.
In the context of this guideline, conditional recommendation would be applicable in specific situations where factors such as strong patient preference, limiting circumstances, or contraindications would preclude the use of other generally preferable options. |
Once approved by committee chairs, the full-text draft guideline and graded recommendations were compiled and circulated to the full committee. The committee was given three weeks to submit written feedback on the draft guideline. Feedback was collated and incorporated into a revised draft for external review.
External review and stakeholder consultation
The draft guideline was circulated for review and comment to relevant experts and stakeholders in provincial, national, and international jurisdictions as identified by the committee. As per policy, all external reviewers completed disclosure of interest forms prior to review. Feedback from the external reviewers was reviewed by the co-chairs and incorporated into the guideline.
Update schedule
In order to ensure that advancements in the field reach the intended audience in a timely and effective manner, the guideline committee will review and update the guideline regularly.
A1.4 Search methodology
Two limited but systematic literature searches were conducted in December 2019 and May 2022 to identify literature based on the research questions listed below with regard to the management of opioid use disorders. The literature search conducted in May 2019 expanded on the search conducted in 2016 for the first edition of the guideline. The guideline development process was put on hold due to the COVID-19 pandemic shortly after the completion of this search. To address the time gap in the development process, an updated search was performed in May 2022 using the same research questions and inclusion criteria, which was reviewed and approved by the committee chairs. Since the PubMed search site had made significant changes to its functionality in 2020, the same publication date limits (2016 onwards) were applied in 2022 to ensure that no relevant finding would be missed due to these changes; however, the articles identified in the 2019 search were considered duplicates and removed from the results of the 2022 search to avoid redundant work. The PRISMA chart and summary of identified items presented in this appendix presents aggregate results of the literature searches performed for the second edition of the OUD guideline.
Peer reviewed articles and papers were identified by searching health-related databases with international coverage (Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials via Ovid; CINAHL and PsycINFO via EbscoHost). Database-dependent subject headings and text words were used in the search.
Specific search parameters (e.g., inclusion/exclusion criteria, jurisdictions, time frame, languages of publication) were developed in consultation between the information specialist, BCCSU staff, and guideline committee co-chairs during initial planning stages.
Table 5. Inclusion and Exclusion Criteria for the 2019 and 2022 Literature Searches
| Research Question | Include | Exclude |
|
1. Should individuals with opioid use disorder be offered buprenorphine/ naloxone as the preferred first-line option for opioid agonist treatment? |
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| 2. Are there specific individuals with opioid use disorder who should preferentially receive depot buprenorphine or injectable buprenorphine rather than sublingual buprenorphine/naloxone? |
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| 3. Should individuals with opioid use disorder who are not benefitting from buprenorphine/naloxone be offered the option of transitioning to methadone? |
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4. Should individuals with opioid use disorder be offered methadone as a first-line treatment option when buprenorphine/naloxone is not preferred? |
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5. Should individuals with opioid use disorder who have achieved sustained clinical and social stability on methadone, and who express a desire for lower-intensity treatment or treatment simplification, be offered the option of transition to buprenorphine/naloxone? |
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6. Should individuals with opioid use disorder who have not benefitted from treatment with first- and second-line treatment options (buprenorphine/ naloxone and/or methadone) be offered the option of opioid agonist treatment with slow-release oral morphine? |
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7. Should individuals with opioid use disorder be offered the option of withdrawal management as a stand-alone treatment? |
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| 8. Should individuals with opioid use disorder who wish to pursue withdrawal management be offered the option of an extended opioid agonist taper (that is, a gradual dose reduction over a period of one month or more) in an outpatient or residential setting? |
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9. Should individuals with opioid use disorder who have sustained clinical stability on—but wish to discontinue—opioid agonist treatment be offered the option of a long-term stepped tapering schedule (i.e., individually tailored, alternating schedule of gradual dose reduction and stabilization periods with a total duration of months to years)? |
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10. Should individuals with opioid use disorder who are engaged in opioid agonist treatment be offered the option to access or participate in psychosocial treatment interventions? |
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11. Should individuals with opioid use disorder who have achieved cessation of opioid use be offered the option of treatment with naltrexone to prevent lapse or relapse to illicit opioid use? |
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12. Should individuals with opioid use disorder be offered harm reduction services? |
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Limitations:
- Grey literature resources were not searched for this phase of the literature search, although this search was supplemented with targeted structured searches of grey literature.
Identified items
Table 6. Items Identified by Database or Resource Type in the May 2022 Search
| Database Name | Number of Items Identified | Number of items (Duplicates Removed) |
| Medline | 544 |
541 |
| Embase | 584 |
194 |
| CDSR | 9 |
1 |
| CCRCT | 437 |
91 |
| CINAHL | 280 |
27 |
| PsychINFO | 221 |
33 |
| Total - All Sources | 2075 |
887 |
Reference
- Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence
and strength of recommendations. BMJ. Apr 26 2008;336(7650):924-6. doi:10.1136/bmj.39489.470347.AD
The above appendix was developed to support clinical practice using a different methodology from the process utilized for the main body of the guideline.
The clinical guidance provided in the appendix has been derived through guideline committee consensus following iterative discussions in reference to existing evidence and national and international evidence-based clinical practice guidelines.
The content presented in the appendix is also informed by the opinion of expert reviewers, personal communication with study authors, and a review of position papers and practice bulletins issued by recognized addiction medicine professional organizations and authorities. In addition, where appropriate, Health Canada-approved drug product monographs, and previous and current guidance from the College of Physicians and Surgeons of BC (CPSBC) and Health Canada were consulted to ensure compliance with provincial and national safety regulations and standards for practice.