FRAMEWORK DOCUMENT. New HIV Prevention Technologies: Regulatory, policy, programming and research implications for Canada.

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1 FRAMEWORK DOCUMENT New HIV Prevention Technologies: Regulatory, policy, programming and research implications for Canada November 2011 Developed by: With financial support from:

2 Table of Contents Table of Contents... 1 Acronyms... 1 Background... 1 National Consultation Meeting... 2 Purpose of this Framework Document... 2 How This Document is Organized... 2 Priority Action Areas Demonstration Projects and Acceptability Studies with Key Populations Canadian Version of Mapping Pathways National Implementation Guidelines Integrating NPTs into Existing HIV Policies and Programs The Need for Guidance Regulatory Considerations Jurisdictional Considerations Support for Community Engagement Guidelines for Frontline Delivery Communication Strategy on NPTs as One Component of Comprehensive HIV Prevention Epidemiological Monitoring System Improved PEP Access Next Steps Appendix A: Regulatory Review Process in Canada... 12

3 Acronyms ARV BBP CAS CIHR CPHA FPT HPFB HPV ICAD IDU MSM NGO NPT npep PEP PrEP STI TaP TPD Antiretroviral drug Blood-Borne Pathogens Canadian AIDS Society Canadian Institutes for Health Research Canadian Public Health Association Federal, Provincial, Territorial Health Products and Food Branch Human Papilloma Virus Interagency Coalition on AIDS and Development Injection Drug User Men Who Have Sex With Men Non-Governmental Organization New Prevention Technology Non-occupational Post-Exposure Prophylaxis Post-Exposure Prophylaxis Pre-Exposure Prophylaxis Sexually Transmitted Infections Treatment as Prevention Therapeutic Products Directorate Background New HIV prevention technologies (NPTs) can be a critical part of comprehensive HIV prevention. In the Canadian context, NPTs are generally understood to include vaginal and rectal microbicides, postexposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), treatment-as-prevention (TaP) and vaccines 1. Currently, we employ a range of biomedical, socio-behavioural and structural approaches to HIV prevention. NPTs may help to prevent HIV infection among those who cannot use or rely on existing prevention methods such as condoms. However, most stakeholders have limited awareness of NPTs and are ill-prepared to deal with the regulatory, policy and programming implications of recent and impending trial results. In the past year, NPTs have begun to show great promise. 2 Several large efficacy trials recently demonstrated proof-of-concept or established efficacy for pre-exposure prophylaxis (PrEP), microbicides, vaccines and treatment-as-prevention. If the potential of new approaches to HIV prevention is to be harnessed, it is important to advance the dialogue on the concrete policy and programmatic implications of these new technologies within the Canadian HIV prevention landscape. In addition, there are pressing research questions that must be addressed in order to understand better these implications for the Canadian context. 1 For information about each of these NPTs, please refer to the Fact Sheets by AVAC: 2 For a review of NPTs and the most recent clinical trial findings, please view the webinar series offered by ICAD, CAS, CATIE and CPHA, with downloadable materials and recordings at: 1

4 National Consultation Meeting On September 15-16, 2011, four Canadian NGOs (Canadian AIDS Society, CATIE, Interagency Coalition on AIDS and Development, and the Canadian Public Health Association) collaborated, with financial support from the Canadian Institutes of Health Research, to host a national stakeholder meeting in Ottawa. The purpose of the meeting was to engage Canadian stakeholders in identifying implementation issues for NPTs, and based on these, identify research needs and priorities that provide a research agenda for social, clinical and policy researchers. Representatives from relevant stakeholder groups (policy-makers, community representatives, researchers, public health and the private sector) participated in the working meeting to identify the knowledge gaps which should be filled for effective policy and programming decisions to be made in Canada, and to ensure that Canadian stakeholders are appropriately prepared for the introduction of NPTs in Canada. The overall purpose of the meeting was to build preparedness of Canadian stakeholders for the introduction of NPTs and to move the results of research into policy and programming. The meeting achieved the following objectives: o o o Convened an in-person working meeting with relevant stakeholder groups: policy-makers, community representatives, researchers, public health and the private sector; Identified regulatory, policy, programming barriers and issues that need to be addressed; Identified research needs and priorities that will clarify how NPTs may work in the Canadian HIV prevention landscape. Purpose of this Framework Document In advance of the working meeting, the four national NGOs produced a draft of this Framework Document to outline the regulatory, policy and programming barriers and issues that they identified as needing to be addressed, as well as research questions, needs and priorities that they believed should be pursued, related to the introduction of NPTs in the Canadian context. The draft version of the Framework Document was shared with meeting participants to serve as a launching point for the working meeting. Subsequently (after the meeting), the project partners and relevant stakeholders incorporated the input given by participants in the working meeting into the framework document, and intend for this Framework Document to be used as a basis for continued NPT preparedness work for Canada. How This Document is Organized The Framework Document begins with a list of six actions prioritized by Canadian stakeholders. These are actions which have most immediacy for Canadian preparedness from regulatory, program, policy, and research perspectives. The Framework Document then provides more detailed background information and action planning for each of the six priority areas. It should be noted that there is significant overlap between these six priority action areas, and efforts in one area can contribute to the other priority action areas. 2

5 Priority Action Areas a) Demonstration Projects and Acceptability Studies with Key Populations Canadian stakeholders identified the need for pilot or demonstration projects to determine the most effective way for delivering NPTs to different at-risk populations. Research to understand NPT acceptability and access by the populations which would most benefit from the NPTs should also be conducted. b) Canadian Version of Mapping Pathways Mapping Pathways includes a thorough review of the social, economic and clinical impacts of treatment as prevention, as well as microbicides, PrEP, and PEP, in the contexts of South Africa, India and the United States. The project s aim is to provide the research and analysis that communities and policymakers need in order to formulate coherent, evidence-based decisions for HIV/AIDS treatment and prevention strategies in the 21st century. A Canadian version of Mapping Pathways is necessary to fully understand the place of NPTs in the Canadian response to HIV prevention and treatment. c) National Implementation Guidelines Canadian stakeholders placed a strong emphasis on the need for national leadership and stewardship (with multi-stakeholder input) for the development of guidelines and an implementation strategy that is ultimately delivered provincially/locally, to translate regulatory approval to clinical and community practice. This includes guidelines for testing, counselling, risk assessment, adherence support, starting/stopping NPTs, and monitoring safety, side effects, resistance and risk compensation. d) Communication Strategy on NPTs as One Component of Comprehensive HIV Prevention Canadian stakeholders identified a well-developed communication strategy as a priority for NPT preparedness. Specifically, the communication strategy would provide guidelines for service providers on how to deliver NPTs as part of a comprehensive prevention approach. In other words, it would be based on careful consideration of how NPTs could reinforce and increase awareness of, and access to existing prevention services. For example, high-risk individuals requesting access to PrEP could be provided enhanced risk reduction counselling. e) Epidemiological Monitoring System Canadian stakeholders identified the need for enhanced epidemiological monitoring systems that would monitor the reach and access of NPTs, and resultant changes in HIV incidence rates. f) Improved PEP Access Canadian stakeholders prioritized PEP as an NPT which is immediately available, but which is used with great inconsistency across jurisdictions. There is a need to make non-occupational PEP more widely available in Canada, and stakeholders want to work together to improve awareness, access and create policies to standardize PEP access across the country. 3

6 1. Demonstration Projects and Acceptability Studies with Key Populations Most clinical research has taken place outside Canada. Only Université Laval in Québec City has been the site of a phase 1 microbicide trial (and this was a decade ago), and Vancouver, Toronto and Montréal have twice been sites for multi-country phase 3 clinical trials of preventive vaccines. None of the trials testing products that have been proven to be effective at reducing HIV infections have taken place in Canada. This raises the question of applicability of these research findings to the Canadian context. In particular, it is important to consider whether the tested intervention and the study populations have relevance for the Canadian epidemic. For example, as of November 2011, only one late-stage PrEP trial has been conducted among gay men and other MSM (although subsequent trials among serodiscordant couples and heterosexual men and women confirm PrEP s efficacy), and no PrEP trial among IDUs has been completed yet. These two populations together represented 64% of new cases in Canada in This situation might pose challenges for Canadian regulators, policy-makers, service providers and HIV educators. One very notable exception to this situation is TaP. While no late-stage trials to demonstrate its efficacy have been conducted in Canada, the BC Centre for Excellence has been at the forefront of global efforts to scale up access to treatment for its prevention benefits, and BC has demonstrated some success in this area, although not without controversy. Demonstration projects can help to establish optimal ways for community, public and private sectors to work together to deliver NPTs, tailor interventions to be best suited to local and national epidemics, and to understand individual user preferences in the context of social and cultural norms and practices. Some specific issues that would be addressed through such a demonstration project are: understanding what people hear, understand and process regarding risk messages relating to NPTs (e.g., regarding partial efficacy); being able to target particular messages and counselling strategies to be most appropriate for particular populations and individuals; and effective integration of biomedical and the most efficacious behavioural interventions. It would assess, for example, how individuals integrate NPTs into their sexual health practices. A demonstration project may address questions of how to create incentives and behavioural supports for adherence (e.g., by framing microbicides as lubrication and sex enhancing), how to support and promote adherence through established services (e.g., directly observed therapy for ARV treatment), how adherence is affected by side effects, cost and formulations of NPTs, and potential drug interactions with other medications and recreational drugs (e.g., Viagra, club drugs, contraceptives, etc.). The demonstration project would test and identify the best delivery channels for NPTs, and advise stakeholders on how to bridge the gap between clinical and community practice. Finally, important lessons learned and best practices can be gathered from HPV vaccine delivery, female condoms, and type 2 diabetes models of management. We can identify the barriers to using existing prevention technologies such as female condoms and the lessons that can be learned from this when rolling out other NPTs. 4

7 2. Canadian Version of Mapping Pathways As noted above, there has been very little clinical trial research in Canada regarding biomedical prevention approaches. Thus, little is known about the transferability of NPT research to Canadian epidemiological contexts. Furthermore, there have only been a few trials showing efficacy in some populations relevant to Canada, such as gay man and other MSM and serodiscordant heterosexual couples, and none showing efficacy in other populations relevant to HIV prevention in Canada (i.e., IDUs, Aboriginal peoples). A Canadian version of Mapping Pathways 3 would engage policy-makers and community stakeholders in a thorough consideration of treatment and prevention options. A Canadian Mapping Pathways project would involve a comprehensive review of the social, economic and clinical impacts of TaP, PrEP, microbicides, and npep, providing the research and analysis that stakeholders need to formulate coherent and evidence-based decisions for HIV treatment and prevention in the future. In particular, this review would provide the necessary information for policy-makers, community organizations, and public health stakeholders to make evidence-based program and policy decisions about the place of NPTs in the Canadian context. Decisions about the availability of NPTs will depend in part on the balance between benefits that might come from use of the interventions, and the potential risks. This costs-benefits analysis should take into account benefits (e.g. infections averted, saved healthcare costs, increased years of productivity) and costs of any new intervention, including costs of services related to its delivery (e.g. HIV testing, STI testing and treatment, risk-reduction counselling, adherence counselling, monitoring side effects and toxicities). It also includes understanding who in Canada might use the intervention, how they might use it, and what impact that could have on HIV rates. The study would assess the size and characteristics of the potential market for each NPT, and how this would determine appropriate approaches to product introduction and distribution. This analysis would help to determine how to target certain interventions to certain populations in order to maximize benefits and minimize costs and harms. The results of acceptability studies could be helpful in this regard as well. A Canadian Mapping Pathways project would consider which populations and under what circumstances each NPT is likely to be useful, and consider any circumstances/populations for which NPTs might be inappropriate or even harmful. The potential of NPTs will depend largely on the ability of at-risk populations to access them. This will be influenced by requirements for prescriptions, HIV testing, risk-reduction counselling, adherence counselling, monitoring side effects and toxicities and who will foot the bill for these services. The cost of the NPT itself could be substantial, even without those services. A month s supply of Truvada for PrEP can cost $750 or more in Canada. Depending on whether various NPTs obtain HC regulatory approval, how they are scheduled, whether provinces include them on their formularies, and whether insurance companies will pay for them, the cost burden of NPTs could vary tremendously for those most at-risk for HIV who are generally those least likely to pay out of pocket for such interventions. (See Appendix A for an overview of Canada s regulatory approval process). Given the diversity of the HIV epidemic across 3 Mapping Pathways is a multi-national project (South Africa, India, and the US) to develop and nurture a research-driven, community-led global understanding of the emerging evidence base around the adoption of antiretroviral-based prevention strategies to end the HIV/AIDS epidemic. 5

8 Canadian provinces, the cost-benefit trade-off of including each NPT (for particular populations) in provincial drug formularies would have to be assessed for each province. A Canadian Mapping Pathways would allow a comprehensive analysis of all of the interrelated issues which will have significant influence on the value of NPTs for HIV prevention in Canada. 3. National Implementation Guidelines 3.1 Integrating NPTs into Existing HIV Policies and Programs The policy and programming issues relating to NPT preparedness, introduction and roll-out are multiple and complex. Stakeholders across all sectors must work to ensure that NPTs are on the federal HIV agenda on the part of CIDA, PHAC, Health Canada, and CIHR. Key policies and programs (such as Leading Together, the Federal Initiative, and the Canadian HIV Vaccines Initiative) should be updated to reflect current NPT research priorities and implementation issues. Government leadership is also needed in considering the potential impact of policy and program integration between HIV, blood-borne pathogens (BBPs) and STIs on NPT education and delivery for specific populations. Government partners of the Federal Initiative should clarify which federal agency is responsible for leading in the development of implementation guidelines for NPT delivery. Other important implementation considerations include the integration of updated findings regarding NPTs with: prosecutorial guidelines around the criminalization of HIV exposure and non-disclosure; HIV 101 education; and HIV transmission guidelines. All of these issues need to account for complexities introduced by NPTs with respect to viral load, transmissibility and significance of risk. The implementation guidelines would also take into account the risks of coercing at-risk individuals to use NPTs, and consider issues of informed consent and forced treatment. An important element of the implementation guidelines would be ethical guidelines and prevention programs that promote and raise awareness of NPTs, without coercion (e.g., with respect to treatment as prevention), and consideration of the legal and liability issues which may arise from the use of NPTs. 3.2 The Need for Guidance Governments at various levels (health regions, provincial health departments and the federal health departments) need to create and promote policy positions that support an approach to HIV prevention based on cultural and gender analysis and sexual and reproductive health and rights. Community, public health and research stakeholders have called on policy-makers to take leadership in developing national guidelines for NPT implementation, analogous to the national guidelines on HIV testing and HIV care and treatment. 4 Furthermore, these guidelines should be developed proactively, in anticipation of NPT availability. Implementation guidelines should be comprehensive to span the entire process of NPT introduction and delivery in Canada, from the regulatory approval process, to communication and promotion of NPTs, to program and service provider guidelines. 4 PHAC is currently engaged in the development of Comprehensive Guidelines for HIV Testing in Canada, which will provide direction on test planning approaches aiming to increase opportunities for HIV testing among people at risk of HIV infection. PHAC, in partnership with CATIE, supported the development of the 4 th edition of Managing your health: a guide for people living with HIV, which provides up-to-date, reliable, plain language information for PHAs regarding a wide range of care and treatment issues. 6

9 3.3 Regulatory Considerations Implications for implementation of NPTs must be considered early in the regulatory approval process. If Health Canada has authorized a new drug and its manufacturing process under the Food and Drugs Act and Regulations, it provides a Notice of Compliance (NOC). This indicates official approval and permits the drug to be marketed in Canada. Canadian provinces (except Québec) use a national drug scheduling model to align the provincial drug schedules and ensure consistent conditions of sale across the country. At the request of the manufacturer, scheduling recommendations are made to provincial regulatory authorities by the National Drug Scheduling Advisory Committee (NDSAC). A set of factors are used to determine the schedule under which a drug can be sold. These include potential for dependency, adverse reactions, interaction, etc. Canada uses four categories: Schedule I available only by prescription and provided by a pharmacist Schedule II available only from a pharmacist Schedule III available via open access in a pharmacy (over-the-counter) Unscheduled can be sold in any store without professional supervision Given the fact that the most promising microbicides and PrEP candidates are based on ARV drugs, the schedule under which the NPTs can be sold will be an important consideration for regulatory authorities, and must be balanced with issues of accessibility, affordability and privacy. 3.4 Jurisdictional Considerations A key issue for Canadian delivery of NPTs is provincial formulary coverage. Each province decides what drugs it will reimburse (i.e., list on their formulary) for residents eligible under a provincial drug plan. Drug accessibility varies widely between the provinces, which use a number of factors when deciding to list a specific drug, e.g., effectiveness analyses, cost, government priorities and patient advocacy. Some drugs receive a restricted listing if special monitoring is required or their cost is high. While new drugs now go through the Common Drug Review to receive a listing recommendation, generic and existing/revised drugs are submitted directly to the various drug plans to request listing. It would be beneficial to have national guidelines on access to NPTs, but advocates in each province may have to apply pressure to their provincial health departments to have NPTs included in the provincial drug formulary on province-specific arguments of cost-effectiveness and HIV prevention options for people most vulnerable to HIV. Interim guidelines, such as those developed by the CDC, would provide service providers and individuals with information about off-label use of PrEP. These implementation guidelines would ensure proactive consideration of which jurisdictions are responsible for paying for NPTs, and for which populations. The development of implementation guidelines would necessitate federal-provincial dialogue and standardization of guidelines for use and inclusion in formularies. 7

10 3.5 Support for Community Engagement Implementation guidelines would consider if and how specialized resources could be made available to community-based organizations to focus on NPT education, community-based research and advocacy. Funding should also be made available for NPT-focused initiatives in basic and clinical science, social and behavioural science, community mobilization, community-based research and program initiatives, and capacity-building and education initiatives across populations and sectors. 3.6 Guidelines for Frontline Delivery The guidelines may also address the role of health service providers (e.g., physicians, pharmacists, nurse practitioners, ASO workers, harm reduction workers) in testing, prescribing and counselling around NPT use. The implementation guidelines would also consider the implications of each NPT for testing practices and frequency, and provide guidance on how to make use of new testing technologies as part of NPT delivery (such as through home testing, rapid testing, and point of care testing). Social researchers, community-based organizations and government should collaborate to develop guidelines around education, delivery and access to NPTs. The implementation guidelines should also include tools and protocols regarding: a) how to evaluate risk b) how to match NPTs to individual needs c) how to support adherence and manage risk compensation d) how often to conduct HIV testing, STI screening and test for drug resistance e) how to manage side effects for clinicians and consumers f) how to communicate about partial efficacy and effectiveness 4. Communication Strategy on NPTs as One Component of Comprehensive HIV Prevention Explaining a whole range of prevention options that have varying levels of efficacy, safety and toxicity, cost and accessibility among different types of populations will not be easy. It will be necessary to develop tailored messages and communication strategies to meet the needs of various communities, and to explain the characteristics of a range of NPTs. This should be done in a way that integrates NPT messaging into broader HIV prevention and sexual health programs, and addresses stigma, discrimination and criminalization which may impede NPT access. Modelling has suggested that even modest increases in risky behaviours among those who use NPTs could outweigh the partially protective benefit they convey. Communication strategies and messaging must take this into account. Canadian stakeholders identified a well-developed communication strategy as a priority for NPT preparedness. Specifically, the communication strategy would provide guidelines for service providers on how to deliver NPTs as part of a comprehensive prevention approach. In other words, it would be based on careful consideration of how NPTs could reinforce and increase awareness of, and access to existing prevention services. For example, high-risk individuals requesting access to PrEP could be provided enhanced risk reduction counselling. 8

11 The communication strategy would include messages targeted both at population and individual levels. At the most basic level, communication is needed to raise awareness on the current and potential availability of NPTs. It was also noted that Canadian guidelines for assessing HIV transmission risks are out of date, and need to be updated to include the most recent information about transmissibility, concepts of viral load, varying levels of risk, and the currently available options for mitigating that risk. There are certain types of information that community-based organizations (CBOs) and frontline service providers may find difficult to discuss with clients, let alone develop into written or online information resources. Especially difficult to communicate are issues such as sero-sorting, risk probabilities, partial efficacy, the difference between efficacy and effectiveness, and NPT trial results. PHAC is developing new HIV transmission guidelines, and stakeholders should ensure that these new guidelines are amenable to integrating information about NPTs. Training should be provided to community educators and health care providers about how to interpret and communicate efficacy rates, and how to translate this into risk reduction and adherence counselling for individuals. Another important consideration is the advertising guidelines for NPTs. Health Canada is the regulatory authority for drug advertising. Unlike the U.S., Canada permits only limited Direct-to-Consumer Advertising of prescription medications. Advertising in professional journals within the health care sector contains prescribing information. Drug advertisements are reviewed and pre-cleared by two independent agencies Advertising Standards Canada (ASC) and the Pharmaceutical Advertising Advisory Board (PAAB) to determine compliance with the Food and Drugs Act and the various advertising codes. Again, important questions are raised about how to raise awareness about NPTs to consumers who would most benefit without contravening drug advertising regulations. As previously mentioned, most clinical research has taken place outside Canada. None of the trials testing products that have been proven to be effective at reducing HIV infections have taken place in Canada. This raises the question of applicability of these research findings to the Canadian context. In particular, this situation might pose considerable communication challenges for Canadian regulators, policy-makers, service providers and HIV educators. These challenges could be addressed in a communication strategy. Integrating NPTs into existing HIV prevention and sexual health programs will be challenging. Community-based HIV prevention efforts are already under-resourced, and HIV-specific funding is more under threat than ever. Sexual health and general health services are also under strain; they have little time and few resources specifically dedicated to HIV. However, we must be careful to seek a quick fix. Existing low-cost and high-efficacy interventions must not be replaced with high-cost interventions that could have lower efficacy. Behavioural interventions are critical in themselves and to the success of NPTs, and structural interventions must be implemented more broadly. However, NPTs could make a critical difference for those who are at high risk for HIV infection who have not been able to use existing options to mitigate that risk. 9

12 5. Epidemiological Monitoring System Canada s surveillance and epidemiological modeling system is a work in progress. Challenges already exist with respect to FPT standardization around ethnicity data, for example, and our existing HIV surveillance, and monitoring and evaluation system would not be able to measure the efficacy of NPTs once they are rolled out. Effective epidemiological monitoring will be even more vital once NPTs are available, in order to target the appropriate interventions in the most cost-effective way to the most relevant specific populations. Stakeholders need to collaborate to consider the changes that would be necessary, and the feasibility of such changes. Many NPTs have only been made available to several thousand people within the highly controlled setting of a clinical trial. Implementation in real-world settings requires careful monitoring for safety and toxicity concerns. Trials have demonstrated that efficacy is very closely related to adherence rates. For many NPTs, this has a direct influence on the risk of resistance. Therefore, adherence levels and the emergence of possible drug resistance must be monitored carefully. People will need to undergo very regular HIV testing while using ARV-based NPTs to minimize the risk of developing drug resistance. Monitoring risk compensation will be necessary to ensure that NPT introduction doesn t perversely increase HIV incidence. Knowing what impact NPTs have in incidence could help to optimize implementation programs. Finally, community-based organizations and health professionals will have to collaborate to ensure thorough post-market surveillance of NPTs once they are approved and available to the Canadian public. Since clinical trials are controlled and involve a limited number of patients, they generally detect only frequent or common adverse reactions. Even after a new drug is authorized for sale, the manufacturer continues to monitor its safety and study alternative uses. Health Canada maintains regulatory control and monitors adverse reactions (defined as undesirable effects from a product used at prescribed dosages). Under the Food and Drugs Act, drug manufacturers are required to report serious adverse reactions of which they are aware. Health Canada s Marketed Health Products Directorate is responsible for coordinating the consistency of post-market surveillance of drugs and natural health products. It monitors adverse events and investigates complaints and problem reports. Should a product s safety, efficacy or quality come into question, Health Canada will take appropriate action ranging from informing the public and health care community of new product safety information, to removing the product from the market. It would be valuable to create a cohort through demonstration projects (e.g., serodiscordant couples cohort) and to conduct post-market surveillance (phase IV trials) to monitor real-world efficacy, to measure the effects of NPTs on pregnancy and STIs, and to monitor drug resistance over the long-term. 10

13 6. Improved PEP Access A key observation amongst community, public health and research stakeholders is that nonoccupational post-exposure prophylaxis (npep) is a biomedical prevention approach that is already available in Canada, but with significant cross-canada inconsistencies in availability, awareness, and accessibility. Stakeholders agree that access to npep should be improved and standardized across Canada, and that national guidelines are needed. Development of npep guidelines, with leadership from PHAC and in cooperation with provincial public health and community partners, would serve as an ideal model for other NPTs which are not yet available. More standardized and equitable delivery of npep would pave the way for systems that integrate the roles of community-based organizations with the roles of physicians and public health service providers, would test communication guidelines and counselling protocols, and test appropriate targeting to specific vulnerable populations. Wider delivery of npep could also help to establish improved monitoring systems to assess risk compensation, repeated use of npep, drug resistance and adherence issues. These improved monitoring systems should also include social research to understand individuals motivations to use npep, their understanding of concepts such as partial efficacy, and their willingness to tolerate side effects. Next Steps The four national partners CAS, CATIE, ICAD, CPHA will take the lead on moving forward with each of the priority areas, engaging other key stakeholders as appropriate. The membership and mandate of the CMAP Implementation Group should be revisited. The group may want to consider expanding to all NPTs, and identify its role in supporting the national partners to advance these six priority action areas. 11

14 Appendix A: Regulatory Review Process in Canada All drugs sold in Canada both those manufactured here and those imported from other countries must be authorized for sale by Health Canada. Within the Health Products and Food Branch (HPFB), the Therapeutic Products Directorate (TPD) reviews and authorizes new pharmaceuticals and medical devices, and new indications for already authorized products, for their safety, efficacy and quality. There is no clear precedent for establishing regulatory requirements for some NPT products, determining what level of effectiveness would be required for approval and introduction, and establishing what data are needed to support an application for product licensing. Regulatory review requirements will vary significantly amongst various NPTs: Treatment-as-prevention (the idea that anti-hiv therapy may be able to reduce the risk of transmitting HIV) does not require any additional Health Canada regulatory approval. PrEP will possibly require approval for a new indication for already-approved ARV drugs. There are well-established review processes and experience with vaccine approval (e.g., Gardasil HPV vaccine). Microbicides are an entirely new class of products and there is no precedent for their review. There are also vast differences in terms of timing: there is an urgent need to address the issues related to treatment-as-prevention and PrEP, while there is less urgency for microbicides and vaccines. If a new drug passes Phase 3 clinical trials, a New Drug Submission (NDS) may be prepared which includes information on test data; the disease treated or prevented; type of patients (or clients) who could benefit; length of treatment; and the goal (e.g., prevention of HIV transmission). New drugs usually require pre-clinical, clinical, chemistry and manufacturing data. Much of this information is unknown in the Canadian context. We can t say with certainty, for example, which populations would be the best candidates for receiving NPTs. A related issue is uncertainty about prescribing and labelling information and possible caveats (for example, about use with condoms), which could have significant implications for product marketing and pricing. 12

15 What would be the steps in the regulatory review process for an NPT? The NPT sponsor decides that it would like to market a drug in Canada and files a "New Drug Submission" with the TPD. This contains information and data about the drug's safety, effectiveness and quality. It includes the results of the preclinical and clinical studies, details regarding the production of the drug, packaging and labelling details, and information regarding prevention claims and side effects. The TPD performs a thorough review of the submitted information, sometimes using external consultants and advisory committees. The TPD evaluates the safety, efficacy and quality data to assess the potential benefits and risks of the drug. The TPD reviews the information that the sponsor proposes to provide to health care practitioners and consumers about the drug (e.g. the label, product brochure). If, at the completion of the review, the conclusion is that the benefits outweigh the risks and that the risks can be mitigated, the drug is issued a Notice of Compliance (NOC), as well as a Drug Identification Number (DIN) which permits the sponsor to market the drug in Canada and indicates the drug's official approval in Canada. 13