ARCHIVED - Report Stakeholder Workshop on a National Buprenorphine Program

Contact: BCANS Enquiries

November 18, 2004

On this page:

• A. Welcome and Workshop Purpose
• B. Buprenorphine: A Historical Perspective
• C. Buprenorphine: A Physician's Perspective
• D. Buprenorphine: A Regulator's Perspective
• E. Regulatory Framework for Buprenorphine
• F. Buprenorphine: Conditions of Use
• G. A National Buprenorphine Education & Training Program
• H. Next Steps and Closing Remarks
• I. Evaluation
• Appendix I: Meeting Agenda
• Appendix II: Workshop Primer
• Appendix III: List of Participants
• Appendix IV: Participants' Expectations
• Appendix V: Evaluation

A. Welcome and Workshop Purpose

Dr. Siddika Mithani (Director, Bureau of Cardiology, Allergy & Neurological Sciences, Health Canada ) provided the context for the workshop. Health Canada has completed the review of a New Drug Submission (NDS) for buprenorphine and has determined that the data submitted supports the safety and efficacy of the drug for the proposed indication (substitution treatment in opioid drug dependence within a framework of medical, social and psychological treatment) under the following proposed conditions of use:

• supervised daily dosing by a healthcare professional;
• training for prescribing physicians; and,
• maintenance of a list of trained physicians.

The purpose of the workshop is to focus on the implementation of these proposed conditions of use.

Copies of the agenda, workshop primer and list of participants are available in Appendices I, II and III respectively.

Participants' Expectations

Participants were asked to express their expectations for the workshop. The most common were:

1. Proposed conditions of use are optimal to make the drug availability
2. The place of buprenorphine vs. methadone
3. Buprenorphine needs to be made available
4. Feedback on the proposal for an educational program B targeted populations (pharmacists, addiction counsellor, etc.)
5. How buprenorphine is going to be regulated - minimum requirements for an MD to prescribe buprenorphine

A full listing of participants' expectations can be found in Appendix IV.

B. Buprenorphine: A Historical Perspective

Carole Bouchard (A/Director General, Drug Strategy & Controlled Substances Programme, Health Canada ) provided some historical context for the workshop. She briefly reviewed the objectives and outcomes from Health Canada ' s Multi-Stakeholder Workshop on the Management of Drug Therapy in the Treatment of Opioid Dependence held in November 2002. A full report from this meeting was developed and is available through her office. During the next fiscal year (2005/06), a new policy framework for the management of all controlled drug therapies used in the treatment of opioid dependence will be initiated. This will include:

• a review and evaluation of current programs
• development of a policy framework
• stakeholder consultations
• regulatory amendments as appropriate

Experience gained from the implementation of the proposed conditions of use for buprenorphine will inform this process.

C. Buprenorphine: A Physician's Perspective

Dr. Meldon Kahan (Medical Consultant, Centre for Addiction and Mental Health) presented a clinician ' s case for buprenorphine in Canada . He reviewed the drug ' s safety profile, use by primary care physicians and role in treatment. He stressed the importance of patient access to treatment in the primary care setting and supported the concept of a national education program supported by the development of a " registry " of trained physicians.

D. Buprenorphine: A Regulator's Perspective

Dr. Robert Peterson (Director General, Therapeutic Products Directorate, Health Canada ) stressed the importance of a commitment to the development of a risk management program for buprenorphine prior to the issuance of the Notice of Compliance (NOC). The program must be founded on the three proposed conditions of use. If successful, it could serve as a model for other products in the pipeline. The participation of provincial and territorial licensing authorities of pharmacy and medicine and their members will be key to the success of this and future programs.

E. Regulatory Framework for Buprenorphine

Theresa Schopf (A/Head Policy Section, Office of Controlled Substances, Health Canada ) reviewed the international and domestic regulatory framework currently in place for buprenorphine. Buprenorphine is currently listed under Schedule I of the Controlled Drugs and Substances Act (CDSA) and on the Schedule to the Narcotic Control Regulations (NCR); therefore, it is subject to a greater level of control than permitted by the Food and Drugs Act. Offences and penalties for unauthorized activities such as possession, trafficking and possession for the purpose of trafficking, and double doctoring are stated in CDSA and the NCR. This regulatory framework provides effective mechanisms to control and monitor the production and distribution of buprenorphine thereby minimizing the potential for diversion and misuse of the drug.

F. Buprenorphine: Conditions of Use

Dr. Mithani reiterated the three proposed conditions of use for the drug:

• supervised daily dosing by a healthcare professional;
• training for prescribing physicians; and,
• maintenance of a list of trained physicians.

The proposed conditions of use have been developed on the basis of the data submitted to support the authorization of buprenorphine in Canada .

The manufacturer must provide a letter of commitment for implementation of these conditions prior to issuance of the NOC for the drug.

Following completion of the morning's presentations, participants were asked:

1. What key messages did you hear?
2. What were your reactions?
3. What are your concerns and recommendations?
4. What other questions do you have?

Participant responses are detailed in Appendix IV

G. A National Buprenorphine Education & Training Program

Dr. Patrice LaRose (VP, Regulatory Affairs, Drug Safety and Medical Services, Schering Canada Inc.) and Richard Arlen (Product Manager, Schering Canada Inc.) presented a framework for the development of a health care professional education program for Subutex^® (buprenorphine) in Canada . The objectives of the education program would be to:

• ensure the safe and effective use of Subutex^®
• minimize the potential for the diversion and/or misuse of Subutex^®

The program sponsored and supported by Schering Canada Inc. would consist of five modules. It would be targeted to medical practitioners, pharmacists/nurses and drug and alcohol addiction support personnel. Key elements of the framework for delivery of such a program would include:

• development of an outline for a national health care professional training program acceptable to Health Canada
• establishment of a National Subutex^® Medical Advisory Board to assist in development of the education program, local trainers and a national consensus paper on the role of buprenorphine in treatment
• development of partnerships with national health care professional associations (e.g., Canadian Society of Addiction Medicine) to implement the training.

Schering would also support physician certification based upon completion of the training program and communication of this information with P/T colleges. Dr. David Marsh (Canadian Society of Addiction Medicine) noted that CSAM board members had expressed support for that organization to maintain a list of trained physicians which could be shared as required with P/T colleges.

Following completion of this presentation, participants were then asked:

1. What did you like about what you heard?
2. What are your concerns and recommendations?
3. Any other ideas?

Participant responses are detailed in Appendix IV

H. Next Steps and Closing Remarks

Dr. Mithani thanked participants for their valuable input. The meeting demonstrated general support for the three proposed conditions of use. Based on this outcome TPD will work with Schering Canada Inc. to revise and finalize the product monograph for Subutex^® based on the three proposed conditions of use. The NOC will be issued when this process is complete and the manufacturer submits a letter of commitment to TPD that the product will not be launched until the proposed conditions of use are implemented. It would be reasonable to expect that this could occur prior to the end of the calendar year.

I. Evaluation

Participants were asked to complete an evaluation form. Appendix V provides a synthesis of the comments.

Appendix I: Meeting Agenda

Stakeholder Workshop on a National Buprenorphine Program
Health Canada
November 18, 2004
Lady Elgin Room
Lord Elgin Hotel, Ottawa

Agenda

8:00 Continental Breakfast

9:00 Welcome and Workshop Purpose
Dr. Siddika Mithani, Director, Therapeutic Products Directorate

Agenda Review and Participant Expectations
Round of Introductions
Kathleen Connelly, Intersol Facilitator

9:30 Buprenorphine: A Historical Perspective
Carole Bouchard, A/Director General, Drug Strategy and Controlled Substances Programme

9:45 Buprenorphine: A Physician's Perspective
Dr. Meldon Kahan, Medical Consultant, Centre for Addiction and Mental Health

Question and Answer Session

10:15 Health Break

10:30 Panel Presentations:

Buprenorphine: A Regulator's Perspective
Dr. Robert Peterson, Director General, Therapeutic Products Directorate

Regulatory Framework for Buprenorphine
Theresa Schopf, A/Head Policy Section Office of Controlled Substances

Questions of Clarification

11:15 Buprenorphine: Conditions of Use
Dr. Siddika Mithani

11:30 Questions of Clarification

11:45 Launch of Table Discussions

12:00 Working Lunch

Table Discussion: What key messages did you hear? What were your reactions? What other questions do you have?

13:00 Plenary Sharing

14:15 A National Buprenorphine Education & Training Program
Dr. P. LaRose, Richard Arlen, Schering Canada

Table Discussion: Likes? Concerns and Suggestions? Other Ideas? Plenary Sharing

15:15 Health Break

15:30 Plenary Discussion

15:50 Next Steps and Closing Remarks
Dr. Siddika Mithani

16:00 Meeting Close and Evaluation

Appendix II: Workshop Primer

A National Program for Buprenorphine (Subutex^®)
Primer for a Stakeholder Workshop
November 18, 2004

1. Issue:

Implementation of a national program to ensure the safe and effective use of buprenorphine hydrochloride sublingual tablets (Subutex^®) under its proposed conditions of use.

2. Background:

Buprenorphine is an opiate agonist/antagonist indicated for substitution treatment in opioid dependence. It is listed under Schedule I of the Controlled Drugs and Substances Act (CDSA), with other narcotics as well as on the Schedule to the Narcotic Control Regulations.

Although not currently marketed in Canada , buprenorphine sublingual tablets have been approved in France since 1996 and in the United Kingdom since 1999 for substitution treatment in opioid dependence. Other jurisdictions in which the drug has received market authorization include the United States and Australia.

Health Canada has completed the review of a New Drug Submission (NDS) for buprenorphine and has determined that the data submitted supports the safety and efficacy of the drug for the proposed indication (substitution treatment in opioid drug dependence within a framework of medical, social and psychological treatment) under the following proposed conditions of use:

• supervised daily dosing by a healthcare professional;
• training for prescribing physicians; and,
• maintenance of a list of trained physicians.

3. Summary of Pre-market Evaluation

In the clinical trials submitted, buprenorphine was shown to be a safe, effective and well-tolerated therapeutic option for the treatment of opioid dependency. The safety of buprenorphine was studied under conditions of daily intake supervised by a healthcare professional. In all clinical trials, including studies up to one year in duration, take-home doses of buprenorphine were only allowed over weekends and holidays.

As with other opiate agonists, respiratory depression associated with the use of buprenorphine has been reported, especially when misused by the intravenous route or when used together with benzodiazepines.

4. Summary of Post-market Safety Evaluation

Accumulated post-market data, principally from France have suggested that the drug in the sublingual formulation can be subject to abuse and/or misuse. The abuse/misuse episodes associated with the use of buprenorphine appear to arise from the behaviour of the intended treatment population of opioid abusing patients, where opportunities arose due to relatively less controlled distribution.

Individuals have been known to crush the tablets and inject them intravenously, resulting in a number of adverse events related to injection site reactions, such as necrosis, in some cases resulting in amputations of limbs. Other serious adverse events include heart block, respiratory insufficiency, asphyxia and pericarditis.

The post-market evidence revealed potential strengths and weaknesses of several control approaches. The review concluded that prior to marketing an adequate system of controls must be developed to ensure that the benefits observed in the carefully supervised controlled clinical trials were obtained, without undue risk of misuse or abuse.

5. Control Measures: International Experience

Australia

In Australia , individual states are responsible for central monitoring and regulation of the prescribing of buprenorphine. The Federal Government is responsible for collating National Buprenorphine Treatment Data collected and submitted by the states. Data include: number of individuals registered in treatment; number of new and re-admissions; deaths of individuals in treatment.

National Clinical Guidelines and Procedures for the use of buprenorphine in the Treatment of Heroin Dependence have been developed and endorsed by the Royal Australian College of General Practitioners, the Royal Australian College of Physicians and the Australian Professional Society of Alcohol and other Drugs. These Guidelines recommend that prescribing privileges be restricted to physicians that possess knowledge of clinical guidelines and skills related to the treatment of opioid addiction. Jurisdictions are advised to develop professional training programs for buprenorphine prescribers and assess the competence of medical practitioners wishing to be approved as buprenorphine prescribers. Although these Guidelines recommend supervised dosing; it is recognized that prescribers may choose to authorize regular or " one-off " takeaway doses for individuals receiving maintenance therapy. More generally, the authorization of takeaway doses is subject to guidelines established in each jurisdiction.

France

In 1996, when buprenorphine was first marketed in France , the drug was made available on prescription, with no further restrictions. Since that time, several label changes have resulted in the strengthening of the prescribing information. The current prescribing information contains a warning concerning supply limitations, i.e., it is recommended that buprenorphine initially be dispensed on a daily basis, and consideration may be given to allowing a seven day take-home supply only once the physician gains confidence in the patient. Moreover, " boxed " text now recommends that buprenorphine be used within a network consisting of specialized addition treatment centres, prescribing physicians and dispensing pharmacists. This strategy, in addition to ensuring a comprehensive treatment plan, provides a mechanism to facilitate patient follow-up.

United Kingdom

In the UK , the Royal College of General Practitioners has developed a guidance for the use of buprenorphine for the treatment of opioid dependence in primary care. These Guidelines remind practitioners that they should only prescribe and treat at levels of practice with which they feel competent and for which they have received adequate training. They recommend that buprenorphine be dispensed daily and that consumption if possible be supervised by the pharmacist for a period of time of at least three months.

United States

Buprenorphine received approval for the treatment of opioid dependence from the United States Food and Drug Administration (FDA) in October 2002. It was the first narcotic drug for the treatment of opiate dependence permitted to be prescribed in primary care settings by specially trained physicians. The decision to permit office-based treatment for buprenorphine was aimed at greatly expanding access to opiate dependence treatments. Up until this time, other treatments such as methadone could only be dispensed in the very limited number clinics that specialized in addiction treatment.

To support its introduction, a comprehensive risk management program designed to deter the abuse and diversion of buprenorphine from its legitimate use was developed by the drug sponsor in collaboration with the FDA. Key components included: education, tailored distribution and supervised dose induction. Physicians were permitted to prescribe take-home supplies of medication as patients progressed on their therapy. Other restrictions included physician registration and limitations on the number of patients he/she was allowed to treat. To qualify to be registered, physicians must complete at least eight hours of approved treatment in opioid addiction or have certain other qualifications as defined in legislation.

6. Summary

Buprenorphine has been marketed in other jurisdictions for a number of years. In each instance measures have been developed and implemented aimed at ensuring the safe and effective use of the drug while minimizing the potential for its abuse and misuse. Health Canada ' s review of the NDS for buprenorphine concluded that similar measures are needed to be developed and implemented in Canada prior to the product ' s launch.

Since buprenorphine is already listed under Schedule I of the CDSA and on the Schedule to the Narcotic Control Regulations, it is subject to a greater level of control than permitted by the Food and Drugs Act. The following activities which one could expect to be conducted illegally in regard to buprenorphine are prohibited: unauthorized possession; trafficking and possession for the purpose of trafficking; and double doctoring. Significant penalties are also attached to contravention of these prohibitions. Similar regulatory requirements for the control of buprenorphine are also in place internationally and limit the potential for diversion and misuse of the drug.

Similar to the regulatory controls established in other jurisdictions, Health Canada proposes the following conditions of use for buprenorphine in Canada :

• supervised daily dosing by a healthcare professional;
• development and delivery to prescribing physicians nationally, a Health Canada approved training programme on the safe and appropriate use of buprenorphine;
• development and maintenance of a list of Canadian physicians that have completed the training programme.
  
  The stakeholder workshop on November 18, 2004 will focus on the implementation of these proposed conditions of use.

Appendix III: List of Participants

Stakeholder Workshop on a National Buprenorphine Program
Health Canada
November 18, 2004

Participants List

• Mr. Richard Arlen
  Product Manager
  Schering Canada
• Ms. Carole Bouchard
  A/Director General
  Drug Strategy and Controlled Substances Programme
  Health Canada
• Dr. Suzanne Brissette
  Canadian Society of Addiction Medicine
• Ms. Connie Coté
  Director of Professional Affairs
  The Federation of Medical Regulatory Authorities of Canada
• Mr. Greg Eberhart
  Registrar
  Alberta College of Pharmacists
• Dr. Doug Gourlay
  Centre for Addiction and Mental Health
• Mr. Wade Hillier
  Manager, Government Programs
  College of Physicians and Surgeons of Ontario
• Dr. Meldon Kahan
  Centre for Addiction and Mental Health
• Dr. Patrice Larose,
  VP, Regulatory Affairs, Drug Safety and Medical Services
  Schering Canada
• Dr. Lowell Loewen
  College of Physicians and Surgeons of Saskatchewan
• Dr. David Marsh
  Canadian Society of Addiction Medicine
• Dr. Siddika Mithani
  Director
  Therapeutic Products Directorate
  Health Canada
• Mme. Josée Morin
  Inspecteure-conseillère professionnelle
  Adjointe à la directrice des services professionnels
  Ordre des pharmaciens du Québec
• Dr. Brenda Osmond
  Deputy Registrar
  College of Pharmacists of British Columbia
• Dr. Cathy Petersen
  Manager
  Central Nervous System Division
  Health Canada
• Dr. Robert Peterson
  Director General
  Therapeutic Products Directorate
  Health Canada
• Mr. Ken Potvin
  Executive Director
  National Association of Pharmacy Regulatory Authorities
• Dr. Marcel Provost
  Collège des médecins du Québec
• Ms. Karen Reynolds
  Associate Director
  Therapeutic Products Directorate
  Health Canada
• Ms. Theresa Schopf
  A/Head, Policy Section
  Office of Controlled Substances
  Health Canada
• Mr. Randy Steffan
  Federal Health Affairs Manager
  Schering Canada
• Mr. Greg Ujiye
  Manager, Pharmacy Practice
  Ontario College of Pharmacists
• Dr. Lloyd Westby
  Physician
• Ms. Stephanie Yung-Hing
  Policy & Strategic Planning Directorate
  Health Canada

Facilitators

• Ms. Kathleen Connelly
  Intersol Group Ltd.
• Ms. Pauline Gaudry
  Health Canada

Meeting Administration

• Ms. Meghan McLaren
  Therapeutic Products Directorate
  Health Canada

Appendix IV: Participants' Expectations

Summary of Expectations:

• More treatment options available for patients
• The place of buprenorphine vs. methadone
• Buprenorphine needs to be made available
• Safety profile is exquisite
• To have a plan and time line to make buprenorphine available within 6 months
• Feedback on the proposal for an educational program B targeted populations (pharmacists, addiction counselor, etc.)
• How buprenorphine is going to be regulated B minimum requirements for an MD to prescribe buprenorphine
• To learn from Health Canada what their proposed framework, expectations, and guidance look like from a practical perspective, and what this means in terms of decision/time lines for issuance of an NOC. To get a handle on the practical implementation issues, so that these can be clearly articulated to other stakeholders to ensure buy in.
• To understand what support will be in place and what reciprocal relationships or expectations there are, to enable information of education and implementation systems.
• Agreement to move forward
• Better understanding of the issues
• Fluid way to erase barriers
• Proposed conditions of use are optimal to make the drug availability

Table Report: Buprenorphine - Conditions of Use

1. Key Messages

• Everybody wants buprenorphine on the market in Canada. It's time to move forward.
• Less regulated than methadone framework. Controlled by education not regulation.
• A training program is essential.
• Clinical need for this product.
• Health Canada anxious to generate NOC soon.
• Health Canada has expectations of provincial medical regulatory bodies, the implication of which are not completely clear.
• Conditions within product monograph proposal are not changes to existing regulations.
• Supervised daily dosing is expected to be part of the product monograph however Health Canada would be open to a phase IV clinical trial on take home doses supporting a revision to the monograph.
• Physician and Pharmacist training would be supported by the manufacturer.
• List of trained physicians will be maintained by a third party (other than Health Canada or manufacturer) and does not have a regulatory role for Health Canada.
• NOC is proposed to be issued subject to 3 conditions for use:
  1. Supervised daily dosing
  2. Maintenance of list of trained physicians
  3. Training for prescribing doctors
• Conditions for use are recommendations from Health Canada, that the manufacturer (sponsor) has a stewardship responsibility.
• Conditions are based on clinical trials provided to Health Canada.
• Buprenorphine has potential for abuse.
• Will product be used for daily dosing B safer environment?
• NIDA in US supports B development of Canadian body of experts.
• Suboxone might reassure.
• Cost is an issue in daily dosing
• Phase IV initiative at take home dosing.
• Clinical trial may take long.
• Suboxone and Subutex^®
• Daily dosing
  • Level of evidence
  • Provincial partnership in resources i.e. lists
  • Clarification B is this for IV users only
  • White paper B submission to Health Canada
  • Best practices B consensus is the best practices
  • 2005 - Suboxone

2. Reactions

• Reactions to daily dosing
  1. Likely "off label" carries would start
  2. Costly to system
  3. But a good safe guard
• MD Training
  1. Good idea
• Registry
  1. No opposition
  2. Probably a good idea
• In general it appears some or all of the three conditions will be necessary for licensing. Given that there was no strong opposition to the three conditions. In fact, the conditions seemed nicely interlinked and supportive of one another.

3. Concerns and Recommendations

1. Concerns: Promoting wider awareness about the safe and effective use of Buprenorphine
   
   Recommendations:
   • Education of healthcare professionals who interface with patients (physicians, pharmacists, counselor nurses)
   • Public awareness programs
2. Concerns: Daily Dispensing
   
   Recommendations:
   • National Medical Advisory Board
3. Concerns: List of trained physicians and issues of access and privacy
   
   Recommendations:
   • Provincial medical licensing bodies may require access.
   • Would patients seeking treatment have access for this purpose?
4. Concerns: Role of pharmacist not addressed in labeling
   
   Recommendations:
   • Perhaps not require pharmacist training in monograph but ensure it is supported; balance access to against quality of care.
5. Concerns: Supervised daily dosing and implications for compliance by prescribers and time for pharmacists.
   
   Recommendations:
   • Ensure adequate compensation for pharmacy staff.
   • Initiate Phase IV trial (open trial) of take home doses as soon as product is on the market.
6. Concerns: The need for information for many healthcare providers around the time of products launch (ex. Addiction treatment providers, etc.)
   
   Recommendations:
   • Professional associations of healthcare providers could assist in the dissemination of information (ex. Email distribution to pharmacists through NAPRA).
7. Concerns: Need to train pharmacist, physicians and addiction counselors.
   
   Recommendations:
   • Schering has committed to a general training program for pharmacists and physicians.
8. Concerns: Off-Label Prescribing is the relative risk and liability to practitioners who contribute to (prescribe or dispense) "off label" greater for this product as compared to "off label" practices in other populations
   
   Recommendations:
   • Colleges can only advise when to comply with conditions.
   • Provide good training

4. Other Questions

• How much longer until notice of compliance is signed?

Table Report: A National Buprenorphine Education and Training Program:

1. What did you like about what you heard?

• Based on already tested product B more efficient than starting from the beginning.
• Based on best practices
• Canadian expert group will adapt and ensure evidence-based context.
• Flexibility for adaptation for needs of each Province (core material is there plus specific provincial needs) B Is there a role for National Organizations for example NAPRA?
• Volume of material may be okay for doctors who already prescribe methadone BUT if you don't have experience in the area of addiction medicine this may be overwhelming in one day (again the potential for flexibility).
• Nice Framework
• Good starting point
• Flexible
• Refresher with ease of delivery
• Train the trainer approach
• Lots of links for CME/CPE (pharmacists).
• Live and interactive, small groups, family physician, local flavor
• From the trainer concept
• CME's
• Adaptable training to jurisdiction
• National core training to put everybody on equal footing

2. Concerns and Recommendations

1. Concerns: NDS Missing Counseling: Challenging values and attitudes that could be counter-therapeutic, Stigma, boundary issues.
   
   Recommendations:
   • Reference to opioid dependence
   • Who talked to as National/Provincial associations for training
   • What may be some of costs unexpected - what extent of sponsorship
2. Concerns: The distinction between certification and list of who completed training B Parameters for the list, how used, how has access etc?
   
   Recommendations:
   • Whether or not an exam of competency would be required?
3. Concerns: Small group would like layer group
   
   Recommendations:
   • Open training to other group police, social workers
4. Concerns: Country Specific
   
   Recommendations:
   • Open up issue from other country B best practices B trends in a country
5. Concerns: Special patient population e.g. HIV, depression
   
   Recommendations:
   • Module
6. Concerns: Special patient population e.g. HIV, depression
   
   Recommendations:
   • Module
7. Concerns: Monitoring and Pain omission need to addressing
   
   Recommendations:
   • Implement appropriate modules
8. Concerns: Too didactic, no case presentations involved
   
   Recommendations:
   • Adjust accordingly
9. Concerns: Geographic isolators
   
   Recommendations:
   • Consideration of other medicines of delivery ( www3.addictioncme.com)
10. Concerns: Lack of broader scope? i.e. Methadone buprenorphine Rx, assessment to load on this
    
    Recommendations:
    • Lack of objectivity with sponsorship bias Med. Advisory committee good idea.
11. Concerns: Module 5 (Pharmacy) Needs...
    
    Recommendations:
    • Identifying and solving drug related problems with Buprenorphine
    • Developing pharmacy-based monitoring plans
    • Pharmacist/physician communication B what will doctors want to know
12. Concerns: Distance Delivery
    
    Recommendations:
    • Is it possible to offer via web streaming, teleconferencing, etc. B Essential to ensure that physician/pharmacists in remote locations can participate e.g. (Knowledge transfer)
13. Concerns: Additional modules needed
    
    Recommendations:
    • Treating pain in patients on buprenorphine B acute pain management in patients monitored on buprenorphine.
    • Monitoring patients on buprenorphine (patient-centered monitoring to assess compliance with therapeutic goals and as an extra for discussions with the patients)
    • What are diversion techniques to be aware of(clinical pearls)

3. Any other ideas?

• We need networking opportunities B need to know resources that are available for referral or just for advice
• Mentorship links will be important.
• Consideration of tailored global roll out after NOC complete.
• Consider staying very close to guidelines as per product monograph i.e. (What is evidence based or not)
• Focus on addiction in a non-stigmatized fashion i.e. (The medical approach)
• Switching patients
• Communication module
• Mentoring program/support service (email/phone) e.g. (National web site, chat room)
• Web based
  1. Available to answer clinical (use of experts)
  2. Password protected
  3. All questions available to everyone

Questions for Carole Bouchard

1. What is the thinking about interim measures?
   • The outcome of today will contribute to the interim measures to help shape this program, buprenorphine can be used as a pilot to help contribute to the overall regulatory framework
2. What role does the registry play?
   • The registry will be talked about later today
   • Call it a list of physicians trained
   • Health Canada perspective is to look at safety data
3. People in Canada and buprenorphine?
   • Many communities in Canada do not have access to Methadone
   • Having Buprenorphine available would be positive because general practitioners could prescribe which is important to the treatment assessment

Questions for Siddika Mithani

1. What is the status and reality of label use when prescribing?
   • Off label use is not specified in the regulations; however label use is covered in the Food and Drugs Acts and Regulations, which Health Canada authorizes for sale. The post market can monitor the off label uses through adverse reactions reporting.
   • Moving forward with off label use, the role of the practitioner must be defined through the College of Physicians, or training on who should be prescribing
2. With conditions is it possible for physicians to give patients pills to take home?
   • At this point in time drugs need to be dispensed and supervised
3. What mechanism is in place to ensure conditions are followed?
   • Health Canada has no authority over the College of Physicians and their training of off-label use.
4. There exists a concern for the legal potential for the proposed conditions of use with respect to training.
   
   1. Is there an alternative for a supervised daily dosage?
      • There needs to be a health care professional to dispense a supervised dose
   2. Issues related to affordability and daily dosing
      • There is a need to have the option of methadone as an alternative
      • Health Canada's role is to ensure safety, efficacy and quality of the product
   3. If Health Canada says condition of use is supervised daily dosage can the College of Physicians provide any alternative?
      • As said before off label use and training is not regulated by Health Canada
      • Health Canada would have to evaluate the data through Clinical Trials to ensure that safety/efficacy and quality are met before non-supervised dosing for patients was changed in the product monograph and labeling
   4. Training for pharmacists is crucial for the success of the product
5. Daily Dosage; Is this Canadian data only and why is the international data not being reviewed?
   • The data reviewed by Health Canada was international, and examined in relation to its safety, efficacy and quality for the proposed indication
   • The opinion of the Canadian Medical Practice is needed for off-label or supervised daily dosages with respect to legality for practitioners
6. Is there any component regarding record keeping that would change for pharmacists?
   • There would be no change for pharmacists as stated in the Controlled Drug Regulations
7. Who is responsible for ensuring the pharmacist is providing or filling prescriptions by a trained physician?
   • It is not the responsibility of the pharmacist to check the list of trained physicians before filling the prescription.
8. The manufacturer has a responsibility to maintain databases which address issues of third party information and drug supplies of patients. Health Canada doesn't maintain patient records.

Key Messages: Afternoon

Daily Dosage

• Provincial colleges need to be consistent with Health Canada conditions of use, if not could be a potential barrier in getting buprenorphine on the market
• Have Clinical Trials sent to Health Canada for data review
• National representative group to expedite the approval for "take home" of the drug
• Work with CSAM
• Links Health Canada & NIDA

Table 2 Comments

• Concerns on daily supervised dose
  
  Conditions necessary to support authorization for sale
  1. The need for trained pharmacists
  2. Off-Label and Double Doctoring
     • falls under provincial authority
     • through registry pharmacists have access to help with the problem of double doctoring
     • physicians need to provide conditions as to why they are using off label use
     • how much longer before NOC is signed?

Table 3 Comments

• Promotion of safety and efficacy of buprenorphine to widen awareness (nurses, patient)
• National Advisory Board needed
• A Common system should be more aware and involved about this drug

• A list of physicians trained in the Access to Information and Privacy Act (if patient wants a copy)
  • Who has access to this list?
    • Health Canada needs to know who and why
    • College of Pharmacists does not need access to list because they will fill the prescription regardless
    • College of Physicians may not have sufficient man power to answer calls about the list
    • Health Canada has an opportunity to look at trends from the list
    • Physicians can opt out of being on the list by address privacy
    • Lists are kept for other training purposes
    • College of Physicians needs to know who has had training, which is provided by the list
    • College of Physicians of Quebec would find it useful to have the list for their purposes
  • Who would keep the list?
    • A web based list is suggested
    • Monitoring/Endorsed to prescribe

• The College of Ontario Physicians is trying to get away from auditing and "special drugs"(issues)
• Sponsor has issues to deal with on a provincial level depending upon each provinces needs to ensure conditions are met
• More discussion is needed for who is responsible for what (Federal, Provincial, Colleges)
• Database and it's maintenance (National, CSAM, Online)
• Role of Pharmacists is not identified, however training for pharmacists is needed
• Adequate time for pharmacists to dispense drug will facilitate Clinical Trial in order to allow "take home" vs. supervised dosage by HCP
  • Need to track patient trends
  • Physician accountability
• Need for information for all healthcare providers about the drug, ex. Email list NAPRA

• When will a NOC be issued so training can begin?
  • It will take time before the product is launched on the market by the sponsor
  • Training needs to be done in provinces
  • Meetings with special advisory groups
  • Physicians/Nurses/HCP will be trained and provided information on the drug
  • Commitment from sponsor not to launch drug widely until training is complete
  • Look at training program and other things to add to the Product Monograph

• Physician certification what does it mean?
  • Refers to being trained and on the list

• There are some core pieces missing from the training package
  • Maintenance of the program
  • Management of acute and chronic pain needs to be included in the training

Plenary Training

• Nice framework with a good starting point
• Train the trainer approach
• Links CME & Pharmacists

Concerns

• pain omission
• maintenance
• geographic isolation
• other ways of media presentation

• Look to a broader scope
  • i.e. never treated opioid dependence before

• Objectivity issues created by sponsor
• Stay close to the Project Manager on guidance for training

Table 2 (Training)

1. Likes
   • based on a tested product
   • evidence based
   • advisory committee (Canada)
2. Dislikes
   • acute pain module needed
   • monitory approach around compliance needed
   • mentorship program
   • referrals
   • networking
3. Pharmacy Side
   • what drug related problems should pharmacists know
   • the information is already out there/monitoring

Table 3 (Training)

Likes

• Program is natural
• Law around counseling, with additional boundaries
• Opioid dependence preferred working in Canada
• Who has been approached for EAC
• Sponsorship monetary issues
• Parameters around list, who will see it, maintenance of list
• Exam of competency

Table 4 (Training)

Likes

• Small group training
• Include others such as social workers
• Training for Canada, but awareness of happenings in other countries
• Module on special patient, ex. HIV/AIDS
• Module on switching patients from methadone to buprenorphine
• Web based training with questions and answers
• Distinction between being compliant in order to receive NOC vs. Health Care Professionals and the training and information required to prescribe the product according to NOC
• Need a expert group created for issues on buprenorphine to help physicians better understand how product will work
• Not clear about when the drug is marketed how patients will be reimbursed (will go through a process of Common Drug Review, ex. methadone funded by opioid dependence but not for pain management)
• Special access through formula
  • money is an issue, who will reimburse the patient
• How do we keep you informed?
  • Provide the report from today and from previous workshops
• Issue around FDA
  • Physicians only have a maximum of 30 patients, however not an issue in Canada

Appendix V: Evaluation

The Highs?

• Concise review of Health Canada's needs
• Structure and focus maintained by facilitator
• Excellence of presenters
• NOC for buprenorphine
• Very functional meeting
• Great participation by attendees
• Good, open, multi-disciplinary discussion
• Good facilitator and smooth process
• Good news about short time line expected for action on NOC
• Effective time wise
• Good representation of stakeholders, clinicians, pharmacists
• Vast array of topics covered
• Opportunity to share points of view with other stakeholders
• On time
• Everyone was so positive (how odd!)
• Great start in terms of physician/pharmacist working together, please keep this going
• Opening in where we are
• Good suggestions
• Clear program
• Good presentations
• Very well organized
• Enjoyable to talk to others in the field
• We appear to be near to having this medication available to physicians
• I appreciate Schering's part in the educational program
• The date of Dec, 31/04 to have everything in place is greatly appreciated
• Various stakeholders and views
• High level view of process, good detail of steps
• Open discussion
• Cross pollination of ideas- sharing
• Covering the issues surrounding the NBP
• Engaging in discussion with experts in the field
• The requirements of Health Canada for the use
• The training program was structured
• Well Organized
• The clarification of the condition for the marketing

The Lows?

• None
• There will not be a good uptake of this medication because of daily dispensing
• Some unanswered questions
• Concern that provincial colleges may impose conditions (ex. for audits) that will make this program not appealing to General Practitioners
• Could have used more information on why & when buprenorphine is used vs. other drug options
• Another ten years before we see the first vs. buprenorphine tables in a community pharmacy
• Lack of legal ramifications of a "condition", these have been presented as prerequisites but with no intent/authority from them to enforce
• The discussion around the role of the pharmacist
• The commitments announced are kept

What do we need to do from here to maintain momentum?

• Follow through with Dr. Mithani's closing remarks concerning NOC December deadline
• Email contact within this group
• Quality objective training of pharmacists and physicians
• Compliment education with effective communications strategy that includes Q   A, a fact sheet, and other tools
• Quick formation of expert advisory group
• NOC issued soon as discussed
• Involvement of national pharmacy associations early on
• Early clear discussion on issues of access and privacy for MD list
• Continue to provide feedback to stakeholders regarding the process of the NOC and launch of buprenorphine
• Keep moving
• Follow through on promise/commitments/ and inform all involved
• Continuous and timely information
• Keep us informed (email)
• Do not delay B keep up the energy by proceeding with implementation
• Communicate program
• Move forward on some major recommendations, e.g. National advisory
• Keep in touch with attendees (email)
• Expand to other sponsors and associations
• To gather clinical information to establish our role as a professional association
• To draw guidelines for the use of burprenorphine

Other Comments

• Excellent moving administration
• Well done
• Good presentations, well organized speakers, with open discussion
• More discussion between Health Canada and provincial colleges respective the trend to prescribe "practice conditions" in drugs when issuing an NOC
• I really enjoyed and learned much from this process.
• Very impressed by the professionalism and competence of all attendees
• It is interesting to see that Health Canada will require a commitment letter from the company to the effect that every effort will be done to facilitate the establishment of programs
• Periodical information on the progress of the file.