Pan-canadian public health network council report and policy recommendations on the use of antivirals for prophylaxis during an influenza pandemic

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Executive Summary

At their May 12-13, 2006 meeting, federal, provincial and territorial (FPT) Ministers of Health directed officials to “immediately begin a process aimed at the creation of a national policy recommendation on the provision of prophylactic (prevention) antivirals for use during an influenza pandemic.” The Task Group on Antiviral for Prophylaxis (TGAP), reporting to the Public Health Network Council (PHNC), was created to take on this assignment and developed a workplan to answer the questions of whether or not governments should stockpile antivirals to be used for prophylaxis during a pandemic, and if so, for whom. Issues such as the use of antivirals for prophylaxis during outbreaks of avian influenza, as part of a containment strategy or by private sector or clinical practitioners, fell outside its mandate.

The Canadian Pandemic Influenza Plan for the Health Sector (CPIP) outlines Canada’s population-based, multi-faceted strategy for health sector preparation and response to an influenza pandemic. It has several components, such as surveillance, public health measures, immunization with a pandemic vaccine, public communications, care of the sick and the use of antivirals for treatment. Immunization with a vaccine is considered to be the most effective public health measure during a pandemic. However, development of a vaccine against a novel influenza virus may take at least six months once the virus is identified. Antivirals are likely to be the only specific influenza intervention until such a vaccine is available. A decision to stockpile antivirals for treatment has already been taken. The possible use of prophylactic antivirals is an additional plank in a strong foundation of pandemic preparedness. In order to facilitate planning the CPIP provides a set of planning assumptions which include:

• pandemic activity of moderate severity in Canada;
• the pandemic strain originates outside of Canada;
• the pandemic virus would follow seasonal influenza patterns in terms of high risk groups and epidemiologic parameters such as incubation period.

TGAP identified the goals of the Antiviral Strategy for Canada as contributing to:

• reducing serious illness and overall deaths due to pandemic influenza;
• slowing or potentially stopping the spread of a novel influenza virus; and
• mitigating societal disruption by reducing the impact of absenteeism due to illness in the critical infrastructure sectors.

TGAP members determined that the TGAP recommendation(s) would be framed as a population-based approach, in which measures would be implemented by public health authorities, in collaboration with the clinical care, emergency response and private sectors, as required.

The report provides assessments in several relevant areas. It then describes TGAP’s process for the development of recommendations, including approaches to the selection of potential target recipient groups. Finally, the report presents recommendations for the use of antivirals during an influenza pandemic, together with corollary recommendations.

Assessment

Scientific Considerations:

TGAP commissioned three reports to review the efficacy and safety of anitivirals. While the data is limited, there is adequate evidence to show that neuraminidase inhibitors (including Tamiflu® and Relenza®, the two antiviral drugs currently in our National Antiviral Stockpile) are efficacious in preventing seasonal influenza given either as pre-exposure or post-exposure prophylaxis in healthy populations. However, translating these findings to widespread use on a population basis requires further consideration of expected effectiveness, efficiency, safety, compliance and potential risk of resistance. For example, research shows that compliance (taking a medication as prescribed) tends to decrease the longer a medication is taken. Based on this trend, it is likely that compliance will be an issue with the prophylactic use of antivirals and this tendency will be greater for pre-exposure prophylaxis (taken for 6-8 weeks or more) vs. post-exposure prophylaxis (taken for 10 days). It is also likely that the risk of the virus becoming resistant to the antivirals will increase during a pandemic. Early detection of resistant strains will be important and real-time surveillance for adverse events needs to be established well in advance of a pandemic.

Health System/Logistical Considerations:

Plans are being developed to address the challenges of providing antivirals for treatment. These include the storage of antiviral stockpiles, secure and efficient distribution, and identifying and reaching those who need to receive antivirals. Given that antivirals are a prescription drug, health care professionals must be reassured that there is a sound rationale for prescribing these medications for large groups, in the absence of extensive prior use of these drugs in the Canadian population. Any strategy for prophylactic antivirals should benefit from and build on discussion of these issues as they relate to early treatment.

Legal Considerations:

Governments that choose not to stockpile antivirals for prophylaxis for use during an influenza pandemic could face allegations of negligence. In negligence actions the plaintiff must establish that the Crown had a duty of care toward him or her. The Crown can be exempt from a duty of care, however, where it makes a pure policy decision. Each government should be aware of the difference between its relationship with the public and its relationship with its employees. Any decisions to restrict access to antivirals by creating priority groups should be based on fair, reasonable and rational considerations. Governments should do everything possible to communicate the policy recommendation to all Canadians in a clear and consistent manner. Once an implementation plan is established and communicated, care should be taken to follow it precisely, unless necessary modifications due to new medical, scientific, social, economic, or policy considerations justify a change.

Ethical/Societal Considerations:

The overall aim of any public health program is to optimize the health of a population in the context of equity, social justice and respect for the individual. Thus it is important to weigh the risks and benefits of establishing an antiviral stockpile for prophylaxis and, should prioritization be necessary, ensure that the process is fair with respect to the pandemic preparedness mission, and be transparent. The following objective criteria are proposed as a means of facilitating selection of priority groups:

• contribution towards the goals of reducing serious illness, overall deaths and societal disruption;
• medical need;
• scientific merit; and
• logistics.

Further, because decision-makers have a duty of accountability to their constituents, governments should establish public education/awareness programs to explain the reasons for their decisions and discuss alternative protective strategies.

Federal/Provincial/Territorial Considerations:

The National Antiviral Stockpile (NAS) was established to secure a supply of antiviral drugs for early treatment during an influenza pandemic, and to facilitate equitable distribution and consistent use of this limited resource. The stockpile of 55 million doses has been distributed among provinces and territories on a per capita basis, with costs shared between the federal and P/T governments according to a 60:40 formula. A pan-Canadian policy decision to expand the use of the NAS to include prophylactic antivirals will require transparency across jurisdictions regarding the intent and current status of each jurisdiction’s prophylactic antiviral stockpile (if any). Funding agreements including cost-sharing would be necessary, as would consistent and ongoing communications from governments to the public.

International Trends:

As of Spring 2006, six of eight countries studied for relevant benchmarking information (i.e., US, Mexico, UK, France, Germany, Japan, Australia and Italy) have committed to using antivirals for treatment. Five of these are discussing the use of antivirals for post-exposure prophylaxis, with a focus on health care workers and household contacts. The two other countries are preparing to use antivirals for prevention. These two countries are quite different from each other. One has the smallest per capita stockpile of the eight countries and therefore has chosen to focus on post-exposure prophylaxis of health care workers and other first responders due to its limited supply. This country has not committed to using antivirals as part of a containment strategy and currently does not have enough antivirals to engage in a treatment strategy. The other country has one of the highest per capita stockpiles. This country is intently focused on containment with the objective of delaying spread of the virus until a vaccine becomes available. If containment fails, then the focus will shift to preventing infection among essential service providers and those whose work puts them at high risk of exposure to, and spreading of, the pandemic virus.

Citizen and Stakeholder Deliberative Dialogues:

Eleven professionally-facilitated dialogues were held across the country involving citizens, stakeholders, and target group representatives (i.e., potential recipients of prophylactic antivirals). While there were some discernible differences across the sessions, from a public policy perspective these differences are not significant enough to require variation in the policy recommendation. There was an overall consensus that governments should create an additional national stockpile of antivirals for prophylaxis for specific and limited use. Given the unknowns, including safety, effectiveness, equity considerations, and opportunity costs, there was a general consensus that the use of antivirals for prophylaxis be limited to as few people as necessary to obtain results.

The process elicited core values that participants felt should guide the policy recommendations. Pragmatism rated highest and based on this, participants felt it was important to focus scarce resources on health and emergency workers. However, this was coupled with the notion of reciprocity – that those receiving prophylactic antivirals need to show up for work to be able to keep society functioning. Other strong sentiments included the values of fairness and equity, compassion for the vulnerable, and the need for strong government leadership.

Given the concern about the unknowns of prophylactic antivirals in a pandemic, participants expressed openness to governments taking a decision not to provide prophylactic antivirals as long as the decision is transparent and communicated clearly along with a sound rationale. They also expect that any decision will be revisited as new evidence becomes available. Participants strongly reinforced the need for early and sustained public education.

First Nations and Inuit Considerations:

Given issues of remoteness and a more vulnerable health status, additional consideration (e,g., with respect to logistics) is needed to ensure equitable treatment for First Nations and Inuit. To respect cultural differences, any policy related to antivirals for prophylaxis needs to translate across linguistic, cultural, social and economic divides that exist between western style medicine and First Nations and Inuit approaches to health, including traditional medicines.

Recommendation

TGAP’s extensive deliberations on all key considerations enabled the identification of the issues fundamental to a government decision on the provision of antivirals for prophylaxis. It is suggested that the recommendations and policy should:

• address the goals of the Antiviral Strategy, and implicitly those of the CPIP;
• be based on sound evidence;
• be practical, possible, reasonable and rational;
• be a “considered liability”;
• be affordable and consider opportunity costs;
• include consideration of international benchmarking;
• be transparent;
• ensure a prudent approach to the population-based use of antivirals for prophylaxis; and
• promote consistency across the country.

TGAP’s deliberations have generated two categories of recommendations. The report includes the context, rationale, and consequences of each. It relates the recommendations to the phases of a pandemic as detailed by the World Health Organization. In broad strokes, Phase 4 occurs when there is evidence of increased human-to-human transmission, Phase 5 elevates that to significant transmission between humans, and Phase 6 is the pandemic – efficient and sustained human-to-human transmission.

Recommendation for the use of antivirals for prophylaxis:

1. During the implementation of the early treatment strategy, critical infrastructure workers have access to rapid assessment and early treatment in order to minimize societal disruption (phases 6.1 and 6.2);
2. Early treatment of cases and post-exposure prophylaxis of close contacts should be offered in Canada during the pandemic alert period (phases 4.1, 4.2, 5.1 and 5.2);
3. No post-exposure prophylaxis of close contacts of cases during the early pandemic period in Canada (phase 6.1);
4. No general post-exposure prophylaxis of close contacts of cases during pandemic phase 6.2, with antiviral use focused on treatment of those with influenza;
5. Use of antivirals for outbreak control, involving treatment of cases, and post-exposure prophylaxis of contacts, in closed health care facilities and other closed facilities where high-risk people reside, during phases 6.1 and 6.2;
6. Antivirals for pre-exposure prophylaxis not to be stockpiled by governments for use during pandemic phases 4.1, 4.2, 5.1, 5.2, 6.1, and 6.2.

In summary, the pan-Canadian policy recommendation on the expanded use of the National Antiviral Stockpile (NAS) during an influenza pandemic proposes their its use for population-based prophylaxis in only one phase of the pandemic, namely for post-exposure prophylaxis in the Pandemic Alert Period, specifically during pandemic phases 4 and 5, prior to any significant spread of the virus in Canada. In phase 6, where pandemic influenza is widespread, it proposes that the focus be almost entirely on early treatment, and that the National Antiviral Stockpile only be used for prophylaxis for outbreak control in closed facilities in which people at high risk of poor outcomes reside.

Each component of the above recommendations outline further work that is required. Much of this is captured in the second set of recommendations.

Corollary recommendations:

1. Development and implementation of a comprehensive communication plan on the pan-Canadian antiviral strategy;
2. More research on the use of prophylactic antivirals;
3. Examination of the available science, logistics, and ethical issues regarding the provision of prophylaxis to immunocompromised persons;
4. Examination of a number of key issues related to implementation of the treatment and prophylaxis strategy;
5. Adoption of a consistent policy decision across Canada;
6. Share all TGAP findings and recommendations with other governments once a policy decision has been made;
7. Strengthened occupational health and safety measures, including infection control in health care delivery settings.

TGAP further recommends that a comprehensive communication plan on the pan-Canadian antiviral strategy be developed and implemented. It also recommends that:

• its proposed policy recommendations be combined with steps for systematic monitoring and appropriate management of a pandemic situation as it proceeds, and that, as relevant new data become available, governments be ready to adjust their policies, plans, and priorities accordingly.

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