July 23, 2018

Rapid Evidence Review Summary Integration of Opioid Agonist Therapy (OAT) in Primary Care Settings

A. Background: OAT Guidelines in Primary Care Setting In July 2018, we undertook a rapid review of the literature on primary care-based service models for treatment of opioid use disorder, with a focus on increasing or integrating OAT in primary care settings in order to increase the number of providers prescribing suxboxone. Opioid agonist therapy (OAT) is part of the spectrum of care for people with opioid use disorder (OUD). OAT has been shown to be more effective to withdrawal management alone in terms of treatment retention, sustained abstinence from opioid use, and reduced risk of morbidity and mortality1. Buprenorphine/naloxone (Suboxone) is the recommended first-line treatment for OUD in adults, and youth ≥ 12 years with moderate/severe OUD. Methadone is the recommended second-line opioid agonist treatment if induction with buprenorphine/naloxone is contraindicated or not preferred2. OAT guidelines released by the BC Centre on Substance Use3 indicate that regardless of type of treatment administered, opioid agonist treatment should incorporate the following components: provider-led counselling, long-term substance use monitoring (e.g., regular assessment, follow-up and urine drug tests), provision of comprehensive preventive and primary care, and referrals to psychosocial treatment interventions, psychosocial supports, and specialist care, as required. Further, these guidelines emphasize that across the spectrum of care for OUD, evidence based harm reduction practices should be offered (e.g. Take-Home-Naloxone kits, access to supervised injection sites, education on safe injecting practice etc.). While treatment for OUD have historically been delivered outside of primary care, often in speciality facilities staffed by mental health addiction experts, there is growing recognition of the importance of increasing the capacity and access to OAT in primary care settings4. Primary care-based models for OAT have been found to be roughly equivalent in efficacy and outcomes to speciality treatment facilities in certain populations5, with the added advantage of helping to managing co-morbid health outcomes (e.g. chronic diseases)6. Primary care practitioners and care teams are encouraged to take on addiction care as part of their practice, as they are well suited to diagnosing and treating OUD and supporting long-term recovery.

1 British Columbia Centre on Substance Use and B.C. Ministry of Health. (2017). A Guideline for the Clinical Management of Opioid Use Disorder. Available from: http://www.bccsu.ca/care-guidance-publications/ 2 B.C. Ministry of Health & BC Centre on Substance Use. (2017). Opioid Use Disorder-Diagnosis and Management in Primary Care. Retrieved from: https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/opioid-use-disorder#induction 3 British Columbia Centre on Substance Use and B.C. Ministry of Health. (2017). A Guideline for the Clinical Management of Opioid Use Disorder. Available from: http://www.bccsu.ca/care-guidance-publications/ 4 Hostetter, M. & Klein, S. In Focus: Expanding Access to Addiction Treatment Through Primary Care. Retrieved from: https://www.commonwealthfund.org/publications/newsletter/2017/sep/focus-expanding-access-addiction-treatment-through-primary-care 5 Haddad, M. S., Zelenev, A., & Altice, F. L. (2015). Buprenorphine Maintenance Treatment Retention Improves Nationally Recommended Preventive Primary Care Screenings when Integrated into Urban Federally Qualified Health Centers. Journal of Urban Health: Bulletin of the New York Academy of Medicine, 92(1), 193–213. 6 Walley, A. Y., Palmisano, J., Sorensen-Alawad, A., Chaisson, C., Raj, A., Samet, J. H., & Drainoni, M. L. (2015). Engagement and substance dependence in a primary care-based addiction treatment program for people infected with HIV and people at high-risk for HIV infection. Journal of substance abuse treatment, 59, 59-66.

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B. Context: OUD and OAT in Alberta From 2016 (month) to 2017 (month), 1, 288 people died from apparent accidental opioid poisoning7 in Alberta, notably rates of apparent accidental opioid drug toxicity deaths per 100,000 were three times higher among First Nations people compared to Non-First Nations people8. In Alberta, the rate of unique individuals dispensed methadone indicated for opioid dependence from community pharmacies per 100,000 increased 7% from 2016/2017 (n=4,006) to 2017/2018 (4,355).9 In addition, the rate of unique individuals dispensed buprenorphine/naloxone indicated for opioid dependence from community pharmacies per 100,000 continues to increase, as seen by the 66 per cent increase from 2016/2017 (n = 2,802) to 2017/2018 (n = 4,714)2. Overall, estimates suggest that more than 8,400 Albertans are on OAT for opioid use (2017/18), in addition there has recently been an expansion in public opioid clinics and treatment options which will serve up to 3,500 additional patients each year (triple the number of patients served in these clinics in 2017)10. C. Overarching Model Types Although evidence is lacking with regard to how one model of care performs compared with another, comparative research on these models may not be the most important determinant for informing further diffusion of OAT in primary care settings. Rather, the most effective model of care is likely to depend in part on the specific implementation setting, including unique characteristics of the target patient population (e.g., HIV infection, pregnant, or adolescent), what resources are available locally, expertise available, proximity to an addiction centers, geographic factors and others (Chou et al. 2016). In a systematic review article of primary care models for OAT11, authors reported that coordinated care models (with non-physician team members helping manage patient appointments and lab results) were the among the most common delivery structures studied. This article found that key factors associated with successful programs included integrated clinical teams with support staff who were often advanced practice clinicians (nurses and/or pharmacists) as clinical care managers. However, it should be noted that most studies in this review report patient retention as their primary outcome, further consideration should also be paid to other program outcomes including; opioid use, adherence, safety, treatment satisfaction and patient engagement in care.

7 Alberta Health. (2018). Opioids and Substance of Misuse: Alberta Report, 2018 Q1. Retrieved online: https://open.alberta.ca/dataset/1cfed7da-2690-42e7-97e9-da175d36f3d5/resource/dcb5da36-7511-4cb9-ba11-1a0f065b4d8c/download/opioids-substances-misuse-report-2018-q1.pdf 8 Alberta Health. (2017). Opiods and Substance of Misuse among First National People in Alberta. Retrieved online: https://open.alberta.ca/dataset/cb00bdd1-5d55-485a-9953-724832f373c3/resource/31c4f309-26d4-46cf-b8b2-3a990510077c/download/Opioids-Substances-Misuse-Report-FirstNations-2017.pdf 9 Alberta Health. (2018). Opioids and Substance of Misuse: Alberta Report, 2018 Q1. Retrieved online: https://open.alberta.ca/dataset/1cfed7da-2690-42e7-97e9-da175d36f3d5/resource/dcb5da36-7511-4cb9-ba11-1a0f065b4d8c/download/opioids-substances-misuse-report-2018-q1.pdf 10 Alberta Health. (2018). Alberta’s Response to the Opioid Crisis: Quarterly Report Appendium May 2018. Retrieved online: https://www.alberta.ca/assets/documents/opioid-quarterly-report-addendium.pdf 11 Lagisetty, P., Klasa, K., Bush, C., Heisler, M., Chopra, V., & Bohnert, A. (2017). Primary care models for treating opioid use disorders: What actually works? A systematic review. PloS one, 12(10), e0186315.

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A variety of review articles and reports 12,13,14 characterize diverse OAT models based on broad overarching features, further details regarding primary care OAT models are presented in Table 1. While models reviewed were implemented in the United States, those models with most relevance to implementation in Alberta were prioritized.

12 Korthuis, P. T., McCarty, D., Weimer, M., Bougatsos, C., Blazina, I., Zakher, B., ... & Chou, R. (2017). Primary care–based models for the treatment of opioid use disorder: a scoping review. Annals of internal medicine, 166(4), 268-278. 13 Lagisetty et al. 2017 14 Chou, R., Korthuis, P. T., Weimer, M., Bougatsos, C., Blazina, I., Zakher, B. & McCarty, D. (2016). Medication-assisted treatment models of care for opioid use disorder in primary care settings.

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Table 1: OAT Primary Care Models

Model Type: Characteristics Considerations Advantages Examples and References*

Coordinated Care Model

In a primary care clinic, two different types of HCP actively communicate to share care responsibilities (e.g. nurse case manager, or pharmacist plus a physician).

Level of training and specific-tasks by non-physician providers can vary widely. Availability of additional psychosocial services is highly variable, which could be more difficult for complex patients.

Utilization of a skilled non-physician to offload physician burden. Some indication that this model allows for improved team communication and higher quality of care delivery. Allows for other HCP (e.g. nurse) to help coordinate ongoing care.

(Roll et al, 2015)15 (Alford et al., 2007)16

Coordinated Care Model-Nurse Manager

The nurse care manager performs patient screening, intake, education, observes and supports induction, follow-up, maintenance, stabilization and ongoing medical management with the physician and team.

Requires additional training for nurse managers.

Utilization of skilled non-physician to offload prescribing physician burden, and an emphasis on provider training.

Massachusetts nurse care manager model: http://www.mass.gov/eohhs/gov/departments/dph/stop-addiction/get- help-types-of-treatment.html

15 Roll, D., Spottswood, M., & Huang, H. (2015). Using shared medical appointments to increase access to buprenorphine treatment. The Journal of the American Board of Family Medicine, 28(5), 676-677. 16 Alford, D. P., LaBelle, C. T., Richardson, J. M., O’Connell, J. J., Hohl, C. A., Cheng, D. M., & Samet, J. H. (2007). Treating homeless opioid dependent patients with buprenorphine in an office-based setting. Journal of General Internal Medicine, 22(2), 171-176.

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Model Type: Characteristics Considerations Advantages Examples and References*

The prescribing physician confirms the OUD diagnosis and appropriateness of OAT and co-manages the patient with the nurse care manager.

(LaBelle et al., 2016)17 (Alford et al., 2011)18

Coordinated Care Model-Project Extension for Community Healthcare Outcomes (ECHO)

Model of care for linking primary care clinics in rural areas with a university health system, emphasizing nurse practitioner screening and OAT combined with counseling and behavioral therapies

Requires strong connections between university health systems and primary care clinics. Strong emphasis on educational and outreach components.

Helpful in rural settings, allows for mentorship for OAT prescribing providers including an internet based, audiovisual network for provider education.

ECHO Model: https://echo.unm.edu/nm-teleecho-clinics/opioid/benefits/

Coordinated Care Model- Southern Oregon Model

An informal network of rural primary care clinics that focus on OAT delivery. This model utilizes regular meeting of regional stakeholders and

Relies on provider training and collaboration as well as regional health network support.

Well suited for rural health providers. Grass roots, community-based effort

(McConnell et al., 2016)19

17 LaBelle, C. T., Han, S. C., Bergeron, A., & Samet, J. H. (2016). Office-based opioid treatment with buprenorphine (OBOT-B): statewide implementation of the Massachusetts collaborative care model in community health centers. Journal of substance abuse treatment, 60, 6-13. 18 Alford, D. P., LaBelle, C. T., Kretsch, N., Bergeron, A., Winter, M., Botticelli, M., & Samet, J. H. (2011). Collaborative care of opioid-addicted patients in primary care using buprenorphine: five-year experience. Archives of internal medicine, 171(5), 425-431.

19 McConnell, K. J. (2016). Oregon’s Medicaid coordinated care organizations. Jama, 315(9), 869-870.

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Model Type: Characteristics Considerations Advantages Examples and References*

primary care providers for educations training and development of practice standards around opioid prescribing for chronic pain and OUD treatment.

Depending on setting, limited capacity for psychosocial services and care coordination/integration.

which may promote buy-in from clinicians and community to overcome stigma and resistance to OAT use.

Shared Care Model

Speciality services (e.g. hospital, rapid access addiction clinic, public or private OAT clinic) lead the medication induction process and then later “hand off” patients to primary care providers that offer OAT.

Requires connections with community primary care providers that offer OAT.

Helpful for patients without a regular health care provider.

Rapid Access Addiction Clinic at Saint Paul’s Hospital, Vancouver, BC: http://www.providencehealthcare.org/rapid-access-addiction-clinic-raac (Kahan et al., 2009)20

Shared Care Model - Hub and Spoke

Experts at “hubs”, (specialized drug treatment centers) serve most clinically complex patients, stabilize patients newly starting OAT. After stabilization, some patients are transferred to the “spokes”, which are primary care providers who initiate and continue prescribing for less complex patients.

Requires strong connections between “hubs” and “spokes”. Might not be feasible in areas with significant geographic distance between “hubs” and “spokes”.

-Designed to coordinate addition treatment with medical care and counselling supported by community health teams and services. -Facilitates knowledge sharing and education

https://www.pcpcc.org/initiative/vermont-hub-and-spokes-health- homes http://www.healthvermont.gov/adap/documents/HUBSPOKEBriefingDo cV122112.pdf http://www.leg.state.vt.us/reports/2014ExternalReports

20 Kahan, M., Wilson, L., Midmer, D., Ordean, A., & Lim, H. (2009). Short-term outcomes in patients attending a primary care–based addiction shared care program. Canadian Family Physician, 55(11), 1108-1109.

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Model Type: Characteristics Considerations Advantages Examples and References*

opportunities for primary care providers.

/299315.pdf http://www.achp.org/wp-content/uploads/Vermont-Health-Homes-for- Opiate-Addiction-September-2013.pdf

Other Models

One Stop Shop Model

Based in an existing mental health clinic, this model provides integrated care for HIV and hepatitis C infection, OAT, mental health, primary care and needle exchange. Developed in response to HIV infection in rural Indiana due to needle sharing.

Requires rapid training of willing local providers and required state and federal resources for outbreak response. Reproducibility of this model in other settings has not been assessed.

May be useful for rapid deployment in areas with specific OUD and HIV outbreaks.

(Conrad et al., 2015)21

Multi-disciplinary Model

Two physician disciplines working closely together within the same clinic (e.g. addiction psychiatry and internal medicine)

May be costly and not feasible in all settings.

Can promote more comprehensive behavioural health counseling in addition to

(Fiellin et al., 2002)22

21 Conrad C, Bradley HM, Broz D, Buddha S, Chapman EL, Galang RR, et al. Community Outbreak of HIV Infection Linked to Injection Drug Use of Oxymorhone – Indiana 2015. Morb Mortal Wkly Rep. 2015; 64(16):443–4. 22 Fiellin, D. A., Pantalon, M. V., Pakes, J. P., O'Connor, P. G., Chawarski, M., & Schottenfeld, R. S. (2002). Treatment of heroin dependence with buprenorphine in primary care. The American journal of drug and alcohol abuse, 28(2), 231-241.

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Model Type: Characteristics Considerations Advantages Examples and References*

standard primary care counseling.

Emergency Department Initiation of OAT

This model focuses on emergency department (ED) physician identification of OUD and initiation of OAT followed by instructions for continuation of home induction, stabilization doses and connection to primary care for ongoing management.

Requires strong connections with primary care clinics that offer OAT. Requires ED to be trained in OAT prescribing.

Promising for areas with high prevalence of OUD, and overdose. Helpful for patients who do not regularly access a primary care physician that offers OAT.

(D’Onofrio et al. 2015)23

*includes grey and published literature

23 D’onofrio, G., O’connor, P. G., Pantalon, M. V., Chawarski, M. C., Busch, S. H., Owens, P. H. & Fiellin, D. A. (2015). Emergency department–initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. Jama, 313(16), 1636-1644

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D. Key Model Components: Within each model type there are differences in key components which are tailored in order to ensure relevance within local context. Key components for consideration are outlined below: Care coordination: A core component of successful OAT models were those that involved an integration/coordination of patient care in order to manage issues related to OUD, as well as any, psychological, medical and primary care needs.24 Models of care that used a designated non-physician staff member (e.g. nurse) in the integration/coordination role, were found to help reduce the burden on the physicians while increasing practice efficiency and permitting more patients to be effectively and safely treated. Psychosocial Treatment Interventions and Supports: Varying modalities for the delivery of these supports has been reported in primary care models. While deemed important by providers, and supported by best practice guidelines, relatively few studies have evaluated the comparative effectiveness of different psychosocial interventions given as a component of OAT in primary care based settings. In a review of different trials of psychosocial interventions there were no clear differences in outcomes between the different interventions25. This is consistent with outcomes of different types of psychotherapy in general. Various modalities of psychosocial treatment/support reported in various models included; regular brief counselling by a physician, psychologist led behavioural counseling, nurse led behavioural counseling, referral to off-site psychological services, referral to community and social support services, onsite individual and group counselling, onsite licensed clinical social worker with experience in pain and addiction, onsite peer supported counselling, health promotion, individual and family support and others. Educational and outreach: Although the education and outreach component was not as well-defined in some models, this was viewed as critical for reducing stigma associated with OAT, increasing the pool of prescribing physicians, and increasing uptake, particularly in settings in which stigma is still high26. In a survey of physicians, providers felt that this stigma was rooted in a general lack of training and understanding, which emphasized the need for education for physicians, other health care providers and even the community regarding the effectiveness of OAT27,28. Education was also viewed as critical for improving standards and quality of care. A number of approaches to education and outreach were described, including a Web-based learning network and educational resources, internet-based mentoring by more experienced physicians, meetings of community stakeholders, in-person educational sessions with patient and clinician educational sessions, and others.

24 Lagisetty, P., Klasa, K., Bush, C., Heisler, M., Chopra, V., & Bohnert, A. (2017). Primary care models for treating opioid use disorders: What actually works? A systematic review. PloS one, 12(10), e0186315.

25 Chou, R., Korthuis, P. T., Weimer, M., Bougatsos, C., Blazina, I., Zakher, B. & McCarty, D. (2016). Medication-assisted treatment models of care for opioid use disorder in primary care settings.

26 Chou, R., Korthuis, P. T., Weimer, M., Bougatsos, C., Blazina, I., Zakher, B. & McCarty, D. (2016). Medication-assisted treatment models of care for opioid use disorder in primary care settings. 27 Molfenter, T., Sherbeck, C., Zehner, M., Quanbeck, A., McCarty, D., Kim, J. S., & Starr, S. (2015). Implementing buprenorphine in addiction treatment: payer and provider perspectives in Ohio. Substance abuse treatment, prevention, and policy, 10(1), 13. 28 Chou, R., Korthuis, P. T., Weimer, M., Bougatsos, C., Blazina, I., Zakher, B. & McCarty, D. (2016). Medication-assisted treatment models of care for opioid use disorder in primary care settings.

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A core component of the Hub and Spoke model [as outlined in Table 1] involved outreach to prescribers in the community to increase the number of trained prescriber physicians. Furthermore, the ECHO model of care, that links primary care clinics in rural areas with a university health system, provides mentorship for providers, including an Internet- based, audiovisual network for provider education and provides free prescription training several times per year. ECHO staff also provide patient education 1-to-1 or in group settings. Medication dispensing: This varies widely as dependent on OAT medication, primary care model type, as well as regulatory guidelines. Some models integrate daily-dispended OAT medications in primary care settings for the duration of patient care, however, multiple models have pharmacists supervise dispending of OAT (buprenorphine or methadone)29, 30. As indicated by British Columbia’s diagnosis and management of OUD in primary care guidelines, once a stable dose is achieved, patients can be transferred to receive daily dispensed doses at a community pharmacy or prescribed take-home doses (1-2 week supply), at clinician discretion. Treatment monitoring: Most interventions noted that they used urine drug screening as a tool to monitor adherence to medication and drug misuse. To encourage patient retention, low threshold models do not automatically suspend patients for failing screening for illicit substance31. Further, OUD treatment guidelines indicate that given the chronic nature of OUD, relapse is common, and patients should not be asked to leave treatment if they do relapse32.

Induction type: Twenty-nine studies included in the systematic review by Lagisetty et al. 2017 supervised patient induction in primary care, with frequent appointments and supervised medication dosing. Some home inductions have proved successful for select patients and can make treatment more convenient for patients and providers, this model of induction can also increase patient autonomy.

E. Barriers to Implementing OAT in Primary Care There exist a number of barriers which can hinder the diffusion of OAT in primary care settings in Alberta. A variety of studies have reported that complex regulatory frameworks can hinder the ability of health care provider to prescribe treatment. Currently in Alberta, physicians are able to prescribe buprenorphine-naloxone (Suboxone) to patients following registration with the Triplicate Prescription Program (TPP). Completion of an online prescribing course is recommended by the CPSA. In order to prescribe methadone, physicians require methadone approval from the College of Physicians and Surgeons, as well as specific education and training33. In addition, Alberta nurse practitioners (NPs) can also now prescribe buprenorphine-naloxone (Suboxone) to patients to treat an addiction to opioids. NPs

29 Lintzeris, N., Ritter, A., Panjari, M., Clark, N., Kutin, J., & Bammer, G. (2004). Implementing buprenorphine treatment in community settings in Australia: experiences from the Buprenorphine Implementation Trial. The American journal on addictions, 13(S1), S29-S41. 30 Gossop, M., Stewart, D., Browne, N., & Marsden, J. (2003). Methadone treatment for opiate dependent patients in general practice and specialist clinic settings: outcomes at 2-year follow-up. Journal of Substance Abuse Treatment, 24(4), 313-321. 31 Bhatraju, E. P., Grossman, E., Tofighi, B., McNeely, J., DiRocco, D., Flannery, M., ... & Lee, J. D. (2017). Public sector low threshold office-based buprenorphine treatment: outcomes at year 7. Addiction science & clinical practice, 12(1), 7. 32 B.C. Ministry of Health & BC Centre on Substance Use. (2017). Opioid Use Disorder-Diagnosis and Management in Primary Care. Retrieved from: https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/opioid-use-disorder#induction 33 College of Physicians and Surgeons. (2018). Opioid Agonist Treatment Program. Retrieved online: http://www.cpsa.ca/physician-prescribing-practices/methadone-program/

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must be registered to prescribe TPP listed drugs and also complete necessary training. In studies, the better utilization of NPs and pharmacists in patient management has been seen as an enabler in OAT diffusion, however training and regulatory requirements are barriers34. Beyond the need for reductions in regulatory barriers in prescribing practices, persistent stigmatization of people with OUD, including engrained perceptions of addiction as moral failing, and not as chronic health condition, can impede the willingness of primary care providers to integrate OAT into practice35,36. Further, stigmatization of OAT and OUD amongst other patients, law enforcement, policymakers, and community members can also significantly impede the implementation of this treatment option. There also exist barriers to implementation in terms of institutional support, and the provision of adequate staffing support. In a study conducted by Walley et al. (2008), physicians in Massachusetts who were waivered to prescribe buprenorphine were surveyed37. This study found that of the 235 that answered the survey, 66% had prescribed at least once, and 34% had never prescribed buprenorphine. Of the non-prescribers, the following barriers were reported (in descending order or importance); insufficient office support. insufficient nursing support, lack of institutional support, insufficient staff knowledge, low demand for services, and payment issues. Of the physicians who were already prescribing buprenorphine in their office-based practices, the biggest barriers (in descending order of importance), included: were payment issues, insufficient nursing support, insufficient office support, insufficient institutional support, and pharmacy issues. This study emphasizes the importance of sponsored training for physicians, resources and staffing for coordination and integration of care, provision of non-physician staff with expertise in OUD, as well as offloading burden from prescribing physician.

34 Chou, R., Korthuis, P. T., Weimer, M., Bougatsos, C., Blazina, I., Zakher, B. & McCarty, D. (2016). Medication-assisted treatment models of care for opioid use disorder in primary care settings. 35 Van Hout, M. C., Crowley, D., McBride, A., & Delargy, I. (2018). Optimising treatment in opioid dependency in primary care: results from a national key stakeholder and expert focus group in Ireland. BMC family practice, 19(1), 103. 36 Huhn, A. S., & Dunn, K. E. (2017). Why aren't physicians prescribing more buprenorphine?. Journal of substance abuse treatment, 78, 1-7. 37 Walley, A. Y., Alperen, J. K., Cheng, D. M., Botticelli, M., Castro-Donlan, C., Samet, J. H., & Alford, D. P. (2008). Office-based management of opioid dependence with buprenorphine: clinical practices and barriers. Journal of general internal medicine, 23(9), 1393-1398.