Annex D: Preparing for the Pandemic Vaccine Response to the Canadian Pandemic Influenza Plan for the Health Sector (CPIP) 2006Footnote 1, provides detail about the pandemic vaccination program in Canada, including considerations associated with prioritization of a pandemic vaccine and their implications for planners. The Annex emphasizes that prioritization decisions (if required) will need to be based, in part, on data that will not be available until the pandemic virus has started circulating. The Pandemic Vaccine Prioritization Framework has been developed as guidance for those who will be making the recommendations on whether or not priority groups are required and, if they are, on who will be members of those groups. Note that this prioritization process does not address the larger question of the opportunity costs of using pandemic vaccine with other measures, including those for seasonal influenza. That question is part of a risk assessment process that is distinct from the prioritization process for recipients of vaccine.
Prioritization strategies for pandemic influenza vaccine in other countries have been reviewed in several recent publications.Footnote 2 Footnote 3 Straetemans et al.Footnote 3 looked at 27 countries of the European Union and the Global Health Security Action Group. The authors found general agreement among the countries reviewed on the make-up of several priority groups – health care workers (100% of countries), essential service providers (92%) and high risk individuals (92%); however, the rationales for the choices were not always included in country plans or, if included, the rationales were not always comprehensive. Only one-third of the countries reported consulting ethical experts to guide vaccine prioritization decisions. The discussion in this paper emphasizes the importance of clarifying the goals of prioritization and proposes the inclusion of ethics experts and the results of modelling exercises to help guide the decision-making process.
The United States provides the best examples of comprehensive prioritization processes, both at the state level (for example CaliforniaFootnote 4 and MinnesotaFootnote 5) and at the national level.Footnote 6 Footnote 7 These American approaches include several commonalities:
The US federal guidance on allocating pandemic influenza vaccine identifies vaccination target groups for pandemics of varying severity, using a tiered approach to prioritization.Footnote 7 In contrast the Minnesota recommendations encompass an ethical framework of principles, goals and strategies to guide the pandemic vaccine prioritization process and include a sample rationing plan to illustrate the framework’s application.Footnote 5 While the Minnesota framework is closest to the framework proposed in this document, there are lessons from all of the American approaches that are applicable in the Canadian setting.
Another pertinent approach is provided in the analytical framework for vaccination programs in Canada known as the Erickson De Wals framework,Footnote 8 which is familiar to program planners in Canada. It was developed to assist in the analysis and comparison of potential immunization programs, for example, by national immunization committees (e.g. the National Committee on Immunization and the Canadian Immunization Committee) and their provincial counterparts, but has also been used in a variety of different contexts. The framework includes 58 criteria classified into 13 categories, which are addressed through a series of questions. The criteria and categories used in the Erickson De Wals framework are comprehensive and similar to other pandemic prioritization frameworks that have been reviewed. Thus it provides a valuable framework that can be readily adapted to the purpose of prioritization of individuals for receipt of a vaccine in short supply.
The proposed pandemic vaccine prioritization framework (see Table 1) consists of a series of criteria organized into categories, with key questions identified for each of the criteria. It is adapted primarily from the Erickson De Wals frameworkFootnote 8 but has grouped the criteria and categories to make them more manageable. The key questions have been adapted for a pandemic vaccine prioritization scenario. Two criteria from the Erickson De Wals framework have not been included: cost-effectiveness, because the CPIP indicates that vaccine will be offered to all Canadians; and ability to evaluate, because this will not guide initial prioritization choices, although it is acknowledged that evaluation may affect course corrections.
|1. Scientific evidence||a. Disease characteristics and burden||
How severe is the pandemic?
Who is most affected in terms of illness, complications and death?
Who are the persons most likely to spread infection?
|b. Vaccine characteristics||
Are there any expected population differences in protection from the pandemic vaccine?
Are there any persons who do not need the vaccine?
Is there a need for a second dose? Can a reasonable degree of protection be achieved by a single dose?
Are dose-sparing strategies possible, e.g. intradermal administration?
Are there any vaccine safety concerns?
What is the proposed indication for use and what indication/market authorization has been granted by the Health Canada regulator? What pre-market assessment has been performed, and what post-market surveillance requirements are imposed?
|2. Ethical considerations||Ethical considerations||
What ethical principles and values should be applied?
How do they inform the decision?
Are the recommendations fair and equitable?
|3. Program issues||a. Vaccination strategies||
What strategies might be considered?
Do the proposed strategies support the pandemic goals, and how?
Are there important knowledge gaps that affect choice of strategies, and can these be addressed through timely research?
What is the timing of anticipated vaccine availability in relation to pandemic activity?
What other factors might affect the strategies (e.g. antiviral use, development of antiviral resistance)?
What is the rate of vaccine production, release and delivery?
What is the size and anticipated vaccine uptake of each potential priority group? Is the target population accessible?
|c. Program acceptability||
What are the public and stakeholder values that can inform decisions about vaccine prioritization?
Should there be any alterations because of public or provider perceptions of disease severity or risk of vaccine?
|4. Additional policy considerations||a. Legal considerations||Are there any applicable legal considerations?|
|b. Conformity of programs||
What are other countries doing?
What degree of provincial/territorial variation is acceptable?
|c. Political considerations||Will the proposed prioritization plan be free of controversy, within Canada and in an international context?|
The Canadian pandemic goals provide strong direction to the choices to be made in implementing the pandemic vaccination program. These goals are set out in the CPIP:
First to minimize serious illness and overall deaths, and second to minimize societal disruption among Canadians as a result of an influenza pandemic.
How best to achieve the goals, however, is not clear-cut, as pandemic vaccine could be used in a variety of ways, as discussed in the following sections.
Using the framework to develop a specific pandemic vaccine prioritization plan involves consideration of the evidence related to each of the criteria and the applicable key questions in Table 1, in turn, followed by integration of the results as they apply to potential target groups. A formal weighting system for the criteria is not proposed at this time because it is felt this would be an artificial product that could not be defended. The epidemiological picture (disease characteristics) probably represents the most important consideration in the prioritization discussions. It is expected that the group developing the recommendations will provide a full rationale and identify the factors that weighed heavily in its decisions.
Developing recommendations for prioritization may not be straightforward. Not all of the necessary information is or will be available. Integrating age-based targets (which might be suggested by pandemic epidemiology) with risks from underlying health conditions and with occupational priorities could be challenging.
Potential data and information needs for each of the criteria are outlined in Appendix 1. Some of these data will be available only through special studies, for which protocols and arrangements should be set up in advance. Some measures, such as mortality measures, are open to a number of equally valid interpretations, as described in Section 4.1 below. Consideration of ethical principles and values, and an understanding of public and stakeholder values will help when alternative choices must be weighed.
The following sections highlight the data gaps and some of the potential pitfalls surrounding considerations of the criteria.
There are several key “burden of disease” measures for decision-making about vaccine prioritization, including pandemic severity, attack rate, and the groups most affected in terms of mortality and severe morbidity. Knowledge of the epidemiology of the pandemic and its disease burden is probably the most important consideration in developing vaccine recommendations, including prioritization of recipients.
Mortality data can be expressed in different ways, e.g. as the number or rate of deaths by age or risk group, or as years of life lost (YLL), which can be further refined into years of healthy life lost or working years of life lost. The choice of one of these mortality measures implies an ethical value judgement as to whether some lives (e.g. young persons or elders) are more important than others. YLL is supported by the observation that, in a pandemic, mortality is shifted to younger ages and by the likelihood of reduced vaccine response in seniorsFootnote 9 While there has been ethical debate (though limited) in the published literature on the general basis of age-based prioritization for pandemic influenza vaccine,Footnote 10-12 at this point it is not known which approach to reducing mortality is most acceptable to Canadians.
Burden of disease must also include a consideration of severe morbidity, which can similarly be assessed in different ways (e.g. disability-adjusted life years, long-term versus short-term sequelae, short-term impact on health resources).
Another factor in vaccine prioritization is whether persons who are most likely to spread disease should be given priority in order to reduce the risk to others. Traditionally, one would consider the risk that infected health care workers could pose to their vulnerable patients and the role of children in transmitting influenza within families and the community at large.
While the ideal would be to use Canadian data on disease characteristics, decision-making cannot be delayed if they are not available. It is hoped that detailed epidemiological data will emerge rapidly from the areas first affected by the pandemic. When available, Canadian data can be used to validate or adjust the plan.
The pandemic vaccine is likely to differ from seasonal influenza vaccine in a number of ways (e.g. formulation, side effect profile, number of doses needed) that could affect a pandemic vaccination program. In order to stimulate immunogenicity in a naïve population, the pandemic vaccine may contain an adjuvant or may be a whole-cell product, which could increase the occurrence of local or systemic vaccine reactions. Given the urgency of pandemic vaccine production, the vaccine may be authorized for sale with limited safety data and minimal clinical effectiveness data to guide prioritization recommendations. Because vaccine will be given to large numbers of people within a short time frame, rare side effects may be detected and may affect the risk/benefit ratio in general or for particular groups of recipients as the program unfolds.
It will be important to determine whether there is a need for a second dose for some or for all potential vaccine recipients. If a second dose is needed, its timing needs to be addressed. The question for prioritization is whether to give everyone the first dose before starting second doses, or whether to begin second doses at the minimum effective interval, thus potentially delaying a first dose in some recipients. Optimal individual protection would call for the second dose to be given as soon as indicated (e.g. 3-4 weeks) after the first dose. If vaccine supplies are particularly tight and a single dose is shown to protect against severe outcomes, like death, greater community protection might result from giving one dose to everyone (conferring at least partial protection) before beginning the second dose, as suggested by some modeling.Footnote 13 However, it is possible that the first dose of vaccine will confer little to no protection in some targeted groups, highlighting the need for “real-time” data collection during the pandemic, as well as a plan for mid-term correction in roll-out strategies.
The World Health Organization (WHO) has emphasized the need to strive for equity among countries for pandemic vaccines. Industrialized countries will have access to most of the world’s supply through their advance purchase agreements. In addition, national regulatory decisions (made primarily in the industrialized countries including Canada) can potentially affect other countries and could reduce the global availability of vaccine. Knowing that our decisions have an impact on others, it is important to keep the global picture in mind when decisions are made on the use of pandemic vaccine in Canada.
WHO has recently published guidance on ethical considerations in developing a response to pandemic influenza.Footnote 14 Chapter 3 of the WHO guidelines deals with priority-setting and equitable access to therapeutic and prophylactic measures. The key process recommendations include a way for setting priorities and promoting equitable access that involves society and relevant stakeholders and incorporates pre-established mechanisms for revising decisions, and for timely and accurate information to be provided to the public.
WHO identifies the following key principles that need to be taken into account in developing criteria for use in prioritization:
More and more jurisdictions (e.g. Australia, New Zealand, UK, USA) have developed an ethical framework to assist their pandemic planning.Footnote 15-18 Similarly, the CPIP contains a section called Ethics and Pandemic Planning, which identifies the ethical principles that have been used in national planning.
A number of Canadian provinces have adopted the ethical framework for pandemic planning prepared by the University of Toronto Joint Centre for Bioethics.Footnote 19 Footnote 20 The ethical principles and values identified in this framework and in the CPIP are summarized in Appendix 2, along with comments about their applicability to vaccine prioritization at a time of shortage. Quebec has also developed comprehensive ethical advice for pandemic planning.Footnote 21
Numerous relevant ethical debates are found in the literatureFootnote 10-12 Footnote 22-30 A full analysis of the ethical issues surrounding the vaccine prioritization question is beyond the scope of this document, but issues related to the principles of equity and their application to prioritization decisions must be highlighted. Both the WHO and the CPIP identify equity as an important ethical principle informing pandemic planning. However, there are other ethics principles that also need to be brought to bear, such as utility and optimizing the risk/benefit ratio. Further Canadian dialogue and debate on which principles should prevail under which circumstances would help inform decisions about the prioritization of scarce resources, such as a limited supply of pandemic vaccine.
As outlined earlier, pandemic vaccine could be used in a variety of ways (sometimes competing) to achieve the pandemic response goals.Footnote 10Footnote 22 Footnote 31 For example, to minimize serious illness and overall deaths one could concentrate first on those most likely to get sick or die, and/or one could vaccinate health care workers to maintain the functioning of the health care system and maximize everyone’s chance of optimal health care. Societal disruption is most likely to occur in a moderate to severe pandemic as a result of high absenteeism of the workforce. Vaccination of first responders (police, fire, ambulance) and other essential workers could minimize the additional impact of the loss of these services. Many authors present arguments to make children a high priority.Footnote 32 Footnote 33 Modeling of the impact of different strategies would be valuable and may be available from the Canadian or WHO pandemic modeling networks.
The stated objectives of the pandemic vaccination program in the CPIP do not provide further insight as to which groups might be vaccinated before others to achieve the overall pandemic response goals. These pandemic vaccine objectives are as follows:
It would be useful to develop more specific vaccination strategies to address the pandemic goals. Once the most relevant strategies have been determined, identification of potential vaccine recipient groups is an easier process. (See Appendix 3 for a chart that outlines a range of potential vaccination strategies to address the pandemic goals and potential target groups for each strategy. Note that health care workers and high-risk persons are identified as priority groups in several potential strategies.)
The timing of anticipated vaccine availability may also affect the strategies. Availability between waves may favour prioritization of occupational groups in preparation for the second wave or those in high-transmission settings, such as school children, in an effort to flatten the epidemic curve of the second wave. Vaccine availability at the start of the second wave may lead to prioritizing the individuals who are at high risk of severe disease and complications, especially if immunity is expected to have developed in a significant proportion of other groups during the first wave.
Vaccination strategies also need to take into account the other planned interventions, especially the use of antiviral drugs or convalescent plasma. For example, the development of drug resistance, severe drug shortages or the unavailability of antiviral prophylaxis for health care or other critical infrastructure workers might affect prioritization.
Annex D identifies a series of population sub-groups to be considered for prioritization in a prioritization plan. These population sub-groups are classified into high-risk groups, occupation-based groups, and healthy adults and children. The proposed population sub-groups from Annex D are set out in Table 2, but they will be refined at the time of the pandemic as an early step in the prioritization process.
|Category||Population Sub-Group||Working Definition|
|High risk (of poor outcome)||Groups in which epidemiological evidence indicates increased risk of poor outcome.Table 1 - Footnote 1 *|
|Occupational||Health care workers||Persons who work in settings where essential health care is provided.|
|Public health responders||Persons essential to the public health response.|
|Key health decision-makers||Persons whose decision-making authority is necessary for implementing and maintaining the health response.|
|Pandemic societal responders||Persons who are trained or primarily involved in the provision of an essential service that, if not sustained at a minimum level, would threaten public health, safety or security.|
|Key societal decision-makers||Persons whose decision-making authority will be necessary, at the time of the pandemic, to minimize societal disruption.|
|Healthy children and adults||Healthy children||Individuals 2-17 years of age who do not have a high-risk medical condition.|
|Healthy adults||Individuals, 18 years of age and older, who do not have a medical condition or fit into an age category that would make them high risk and who do not fall into an occupation-based priority group.|
Identifying persons and groups at high risk of poor outcome will depend on epidemiological analysis of who is most likely to develop complications, require hospitalization or die as a result of infection with the pandemic virus. The existing NACI recommendations identify high risk groups for seasonal influenza (see footnote to Table 2) based on age and underlying medical conditions. It is likely that these same conditions will also place persons at high risk during a pandemic. It is also possible that certain age groups will be found to be at higher risk during the pandemic or, conversely, relatively spared. For example, if an H2 pandemic were to occur, persons born before 1968 who were exposed to circulating H2 viruses between 1957 and 1968 might have some pre-existing immunity.
Review of pandemic epidemiology may also identify additional persons or groups at high risk of poor outcome due to additional chronic disease or risk conditions (e.g. obesity, asthma), or other factors such as gender, racial and/or ethnic status, socioeconomic status, geography (e.g. remote and isolated communities), and lack of access to health care. Vulnerable populations or special settings (e.g. correctional facilities) may be identified as potential targets.
Depending on pandemic epidemiology, vaccine availability and other logistical considerations it may be useful to amend the proposed population sub-groups. For example one might want to
The lack of clarity in how sub-groups are defined (e.g. who is a critical infrastructure worker) has hindered efforts, especially at the provincial and territorial (P/T) level, to develop solid estimates of numbers in some potential recipient groups. The concept of including the person doing the task (who could be a volunteer or family member), not just the person with the job title, needs emphasis in occupational settings.
The current pandemic contract calls for Canada to have priority access to at least 8 million doses of monovalent vaccine (containing15 μg of antigen) per month over a 4-month period. GlaxoSmithKline's manufacturing capacity for pandemic vaccine has now exceeded the minimum specified in the contract, although actual production capacity may vary depending on a number of factors specific to the vaccine being produced. These include yield (amount of antigen that can be grown per egg used in production) and the amount of virus antigen per dose that is needed to immunize. Provinces and territories have indicated that they will be able to administer vaccine through local public health agencies as fast as it is produced, even if that were to involve providing one dose to the entire population within a month.
It is important to maximize use of vaccine; therefore, in addition to estimates of target group size, estimates of the anticipated uptake within target groups are relevant in matching up quantities of vaccine available to potential recipients. There are several additional options to consider:
The way in which vaccine will be allocated to provinces and territories is intertwined with prioritization, as it could affect the quantities available for general distribution. Beyond a general recommendation that P/T allocation be on a per capita basis, detailed discussions have not yet taken place on the actual P/T process.
Some of the specific concerns about program acceptability by public and stakeholders include the following:
Although the CPIP is a public document and has included a vaccination priority list in previous versions of Annex D, there has been little public reaction to this list, except for some questioning of the low prioritization of children.
The TGAP (Task Group on Antivirals for Prophylaxis) deliberative dialogue processFootnote 34 explored public and stakeholder beliefs and values in relation to antiviral prophylaxis. The key values emphasized for decision-making were practicality, fairness and equity, compassion for the vulnerable, public awareness and engagement, and government leadership. These results are relevant to vaccine prioritization decision-making (see Appendix 5).
The University of Toronto Joint Centre for Bioethics, through its Canadian Program of Research Ethics in a Pandemic, is currently engaged in pandemic research projects that include stakeholder forums and public consultation about ethical values related to pandemic issues. This should provide helpful guidance when completed.
There are many factors that must be carefully considered in the development and use of a pandemic prioritization framework. If governments choose to create priority groups for the prioritization of a pandemic vaccine, they could face Charter of Rights and Freedoms challenges under section 15 (equality rights) and/or under section 7 (life, liberty and security of the person). It is important for governments that decide to create priority groups, therefore, to retain evidence that the decision to create the lists was based on a sound scientific, social, economic and ethical policy rationale. Governments should be able to demonstrate that the composition of the lists was based on reasonable, fair and rational considerations. Further, the policy decision to create priority lists should be communicated widely in a clear and consistent manner, and the prioritization framework should be followed carefully and precisely unless necessary modifications due to new evidence justify a change.
In Annex D, the Pandemic Vaccine Working Group is identified as having the responsibility for making recommendations for vaccine prioritization. The degree to which prioritization will be necessary will be linked primarily to the rate of vaccine production, which will not be known until production is under way. Provinces and territories have indicated that their capacity to administer vaccine will not be a limiting factor.
There is at present no prescribed specific process for applying the framework. There has been considerable P/T experience with the Erickson De Wals framework using a number of scoring systems tailored to specific circumstances. Such a formal approach, however, may not be necessary or practical in the circumstances, e.g. if the pandemic epidemiology differs little from the usual pattern of seasonal influenza where priorities for vaccination have already been established. In that case the framework would function more as a checklist to ensure that all relevant factors have been considered. It is anticipated that the group developing the recommendations will decide on the most appropriate way to use the framework and that it will provide a rationale for the recommendations and identify the factors that weighed heavily in the decision.
The appendices to this document provide several tools, such as a list of the data and information needs that should be assembled for the Working Group’s consideration (Appendix 1), and a draft discussion tool to assist individuals in assimilating and weighing the information (Appendix 6).
Here is a list of the data and information that will be needed for the prioritization process. This should be gathered, analysed and presented in advance to the group that will be doing the prioritization, to give them the opportunity to identify any additional analyses or information needed for decision-making.
|Ethical principle (CPIP 2006)||Applicability to vaccine prioritization strategy|
|Protect and promote the public’s health||
Underlying premise of vaccination program
(but there are various strategies to do this)
|Ensure equity and distributive justice (fair and equitable distribution of resources based on need)||
Develop fair criteria for prioritization
Multiple possible applications
|Respect the inherent dignity of all persons||Offer vaccine to all; use consistent approach to prioritization decisions|
|Use the least restrictive means||Example of vaccinating schoolchildren to avoid disruptive school closures|
|Optimize the risk/benefit ratio||Maximize the benefit and minimize the risks in prioritization decisions|
|Work with transparency and accountability||
Justify prioritization plan and decisions Public and stakeholder consultation
Widespread dissemination of prioritization framework
|Additional ethical values from U of T Joint Centre for Bioethics ethical frameworkTable 1 - Footnote 1 *|
|Decision-making processes are reasonable, inclusive, responsive||
Fair criteria, consultation process
Open to review as situation changes
|Reciprocity (responsibility of society to support those who face a disproportionate burden in protecting the public good)||
Prioritization for health care workers
Also reciprocal responsibility of health care workers to report to work and accept vaccine if offered
|Trust||Build trust with stakeholders before pandemic occurs; ensure that decision-making processes are ethical and transparent|
|Solidarity||Communication and open collaboration with stakeholders|
|Stewardship||Need to consider benefit to the public good and equity|
|Pandemic goal||Potential vaccination strategy||Potential sub-group priorities|
|Minimize serious illness and overall deaths||Protect individuals against death||
Health care workers
|Protect individuals against severe illness and complications||
Health care workers
|Protect individuals against medically attended illness||
|Preserve functioning of the health care system||
Health care workers
Key health decision-makers
|Prevent outbreaks in health care settings||
Health care workers
Residents of long term care facilities
Family members of long term care residents
|Prevent spread of infection to high risk persons||
Health care workers
Family contacts of high-risk persons
Caregivers of infants and toddlers
Schoolchildren and day care attendees
|Minimize societal disruption||Maintain societal functioning by vaccinating key groups of individuals||
Health care workers
Other societal responders (critical infrastructure)
Schoolchildren (to avoid school closures)
|Protect the community through herd immunity||Schoolchildren and day care attendees|
According to Public Safety Canada, critical infrastructure refers to those physical and information technology facilities, networks, services and assets that if disrupted or destroyed would have a serious impact on the health, safety, security or economic well-being of Canadians or the effective functioning of governments in Canada. The following list indicates the 10 sectors in the National Critical Infrastructure Assurance ProgramFootnote 1 * and provides sample sub-sectors for each sector.
National planning for critical infrastructure protection is under way. Some provinces and territories may be using modified definitions of the critical infrastructure sectors, but the concepts are similar. For example, one provincFootnote 2 ** defines nine critical infrastructure sectors as follows (omitting manufacturing and using slightly different groupings):
Participants supported three goals:
Priority recipients if antiviral prophylaxis were available:
Values emphasized for decision-making:
Source: EKOS Research Associates, Inc.Footnote 34
|Disease characteristics and burden||How severe is the pandemic?||
|Who is most affected in terms of illness, complications and death?||
|Who are the persons most likely to spread infection?||
|Vaccine characteristics||Are there any expected population differences in protection provided by the pandemic vaccine?||
|Are there any persons who do not need the vaccine?||
|Is there a need for a second dose? Can a reasonable amount of protection be achieved by a single dose?||
|Are dose-sparing strategies possible?||
|Are there any vaccine safety concerns?||
|What is the proposed indication for use and what indication/market authorization has been granted by the health care regulator? What pre-market assessment has been performed and what post-market surveillance requirements are imposed?||
|Ethical considerations||What ethical principles and values should be applied?||
|How do they inform the decision?||
|Are the recommendations fair and equitable?||
|Vaccination strategies||What strategies might be considered?
How do the proposed vaccination goals and strategies support the pandemic goals?
|Are there important knowledge gaps that affect choice of strategies?||
|What is the timing of anticipated vaccine availability in relation to pandemic activity?||
|What other factors might affect the strategies?||
|Logistical issues||What is the rate of vaccine production, release and delivery?||
|What is the size and anticipated vaccine uptake of each potential priority group?||
|Is the target population accessible?||
|Program acceptability||What are the public and stakeholder values that can inform decisions about vaccine prioritization?||
|Should there be any alterations because of public or provider perceptions of disease severity or risk of vaccine?||
|Legal considerations||Are there any applicable legal considerations?||
|Conformity of programs||What are other countries doing?||
|What degree of provincial/territorial variation is acceptable?||
|Political considerations||Will the proposed prioritization plan be free of controversy, within Canada and in an international context?||