Podcast: Priority groups for early COVID-19 immunization
Transcript
Diane Kelsall: Immunization with a safe and effective vaccine could help bring the COVID-19 pandemic under control. That is certainly the hope, and multiple groups around the world are part of the effort to develop safe and effective vaccines. But once we do get a vaccine approved for use in Canada, we cannot expect that there'll be enough doses for all Canadians initially, and certainly not all at once. So we have to plan for prioritization within our population. I'm Dr. Diane Kelsall consulting editor for CMAJ. Today I'm speaking with Dr. Caroline Quach, and Dr. Shainoor Ismail. They have co-authored evidence-based guidance outlining which key populations need to be prioritized for early COVID-19 immunization and principles to help guide decision making around COVID-19 immunization programs. Carolyn and Shainoor and their co-authors wrote this guidance as part of Canada's National Advisory Committee on Immunization. This work was supported by the Public Health Agency of Canada. I've reached Shainoor in Edmonton and Caroline in Montreal to discuss. Welcome. Thanks so much for joining me today.
Caroline Quach: Hi, Diane.
Shainoor Ismail: It's great to be here.
Diane Kelsall: This is a really important issue for Canadians and of course, globally. Let's start by if you could tell listeners a bit about who you are and your involvement in COVID-19 immunization in Canada.
Caroline Quach: Sure. So I can start. I'm Caroline Quach, I'm a pediatric infectious diseases and medical microbiologist at CHU Sainte-Justine in Montreal, as well as the Canada Research Chair in infection prevention and control. I'm also a professor in the Department of Microbiology, Infectious Diseases and Immunology at the University of Montreal. My work in the COVID immunization has been mainly as a National Advisory Committee on Immunization Chair. So because of that, and being also the Chair of that particular working group, I've had the pleasure of working with Shainoor and the team, as well as other NACI members on this important topic.
Diane Kelsall: And Shainoor, can you tell us a bit about yourself?
Shainoor Ismail: Sure. I'm a senior medical specialist at the Public Health Agency of Canada, and I've been working with the National Advisory Committee on Immunization for over 10 years. So I get to work with incredible experts like Caroline. I also practice clinically at the Metro City Medical Clinic, which is a clinic that serves marginalized populations, and where we see patients who experience different types of inequities. Before I started working at the national level, I was an associate provincial health officer in Alberta. So I try to bring together all of these perspectives from the patient level to the provincial and national levels when we're developing guidance on an immunization program for COVID-19 that's not only effective, but also equitable.
Diane Kelsall: Now, there are a lot of groups working around the world to develop a vaccine. There's a race to get to a vaccine, but we don't even know when we'll get it or even if we'll get one that safe and effective. And we also don't know how quickly it'll be produced. So can you talk about the importance of a guideline like this one in that context?
Caroline Quach: Sure. So as you mentioned, Diane, you're right, we are seeing a lot of vaccines currently being developed. A lot of them are currently in phase three trials, but we don't know yet which one will be efficacious and safe, and we really have to wait for that data before making any final recommendation. However, even if we have good results, we realize that it will take time to produce sufficient quantities of vaccine. So because initial supplies of vaccines are not likely to be sufficient to vaccinate everyone, we needed to start thinking around how to prioritize key populations, so that when a vaccine or some vaccines are available, we have an efficient, effective and equitable way to allocate these vaccines in Canada in the context of a staggered arrival of those vaccines. And I think one has to realize that although NACI is making this recommendation at this point in time, this is just the first kick at the can, we should say, because depending on the results on the vaccine characteristics of those that are authorized for us, things are going to have to be adjusted as we move forward. So this is really just the start of the conversation.
Diane Kelsall: As you've alluded to already, they're going to be many groups of people who will be a priority for early vaccination. And I know we're going to get into that in a bit. But first, can you talk briefly about how you put together this guidance?
Shainoor Ismail: Sure. There was a lot of work that went into this guidance over a very short period of time, which really is a testament to the dedication of NACI. NACI is an independent external advisory board to the public health agency, and it's made up of recognized experts from across the country who have extensive knowledge and experience in everything from immunology and infectious diseases, to public health and disease modeling. NACI also has a number of ex officio and liaison members from professional associations like the College of Family Physicians of Canada and the Canadian Pediatric Society. So for this guidance, there was a special working group made up of NACI members as well as some external experts. They met multiple times over the summer, and these are all volunteers, they are not remunerated for their time. And to develop the guidance, we reviewed all the available evidence, epidemiological analyses of COVID-19, the vaccine landscape from clinical trial registry data, the Canadian Pandemic Preparedness Plan, we reviewed international guidance, as well as a rapid evidence review of risk factors for severe COVID-19. In addition to considering evidence on what we traditionally referred to as scientific factors, we also considered important issues - issues of ethics, equity, feasibility, and acceptability. And to make sure that these issues are considered systematically and comprehensively, NACI uses a peer reviewed framework that's been recently published, and you can find the analysis of these factors in the full guidance document. We also conducted extensive stakeholder consultations, including a national survey of stakeholders, where we asked them the relative importance of different pandemic immunization strategies. And then, after many sleepless nights of reviewing the evidence and synthesizing it, it was presented to the committee. They deliberated on it, they discussed it and then the evidence was translated into recommendations. And in the end, NACI voted unanimously in favor of every recommendation.
Diane Kelsall: This was a really, really extensive process and you came up with some key populations and some principles. You've alluded to some of those already. What are the key populations that you've identified as being highest priority?
Caroline Quach: So I think that what we need to start with, is to say that NACI recommends that key populations in whom vaccine is deemed safe and effective based on evidence available at the time of vaccine availability, should be prioritized for COVID-19 immunization in the context of limited vaccines. What we are going to present are the groups that we selected, and you have to realize that they're not mutually exclusive and may overlap. So the key populations identified are those at high risk of severe illness and death from COVID-19. For example, those with advanced age and those with high-risk conditions, those most likely to transmit COVID-19 to those at high risk of severe illness and death from COVID-19, and workers essential to maintaining the COVID-19 response. For example, healthcare workers, those contributing to the maintenance of other essential services for the functioning of society, and those whose living or working conditions put them at elevated risk of infection - and that doesn't mean that an infection might be more severe, it's just elevated risk of infection - and where infection could have disproportionate consequences, including Indigenous communities.
Diane Kelsall: Now, you use the term essential workers, how is that defined? It's probably obvious for groups like healthcare workers, but what about teachers, grocery store staff, other people like that? What is an essential worker?
Shainoor Ismail: That is a good question. I mean, of course, it would be ideal if everyone who wanted to be immunized could be immunized to reduce their risk. But unfortunately, that is unlikely, at least initially. So this particular group of essential workers was identified as a key population because no, they can't work virtually, but they have to work because their work is essential for society to function during a pandemic, so they are at a higher risk of exposure to the virus. And by immunizing this population, we can minimize that disproportionate burden of those essential workers, who are taking on additional risks to maintain the functioning of society. And if these workers are absent, that compromises essential services, which then compromises society, but it's a difficult category to define. There's no national list or consensus for essential workers because each province and territory has different infrastructure and different needs. The Department of Public Safety has previously worked to outline some broad categories to consider during pandemic, and that work is referenced in the article. You know, but as we're getting closer to COVID-19 vaccines becoming a reality, the provinces and territories are discussing with the federal government who exactly is captured under these categories, and the goal is to have a harmonized approach to vaccine prioritization for these essential services.
Diane Kelsall: Which will be really important because of course, people in the different provinces and territories will be looking at who gets priority or not. So I think that's a really, really key point. Caroline, you talked about, you use the term "people at high risk". So can you talk about what makes someone high risk for COVID-19 and the evidence behind it?
Caroline Quach: Yeah, good question for which a lot of answers are still to come. But at this point in time anyone exposed to COVID-19 is at risk of becoming infected with a virus, but it's not everyone who may be at higher risk of severe outcomes of the infection. So the Alberta Research Centre for Health Evidence conducted an evidence review to examine the magnitude of association between risk factors for severe COVID-19 outcomes like hospitalization and mortality. The review looked at studies from OECD countries using multivariate analysis to report on the independent contribution of each risk factor while accounting for confounders such as age, sex, race, ethnicity, socioeconomic status, and comorbidities. So if you look in the paper, there's a table summarizing the results. But essentially, the evidence review found that there was a large independent association of severe COVID-19 outcomes with increasing age, and for certain high risk health conditions like obesity or heart failure. Studies treating age in a continuum found that risks for hospitalization and mortality increased with increasing age. For example, there's moderate certainty of evidence for a very large association of hospitalization and mortality in those over 70 years of age compared to those 45 years of age and younger. And their review also found important independent associations of severe COVID-19 with race or ethnicity, low socioeconomic status, homelessness and male sex. When you look at the epidemiological data in Canada, you'll also see that long term care facilities have experienced a large number of outbreaks associated with a high number of fatalities. And there has also been a number of outbreaks in institutions like correctional facilities, work settings like meatpacking plants, and in congregate living facilities like shelters in Canada. So you have to realize that some of those settings have an increased risk that is not only based on data from outbreaks so far, but could also be based on context where infection and outbreaks could have a disproportionate consequences. And that includes indigenous communities, which have so far been quite good at keeping the virus out of the community. But we fully realized that if the virus was to come in, it could have important consequences. That's why they are included in the high-risk population.
Diane Kelsall: You know, one of the things that's been so clear with this pandemic is that certain populations you mentioned, some of these have been disproportionately affected. And Shainoor, you mentioned that NACI used a framework to look at ethics and various aspects to help guide decision making, and so I know that NACI developed some very sound principles to help people with this. Can you tell us a bit about those principles?
Shainoor Ismail: So with any public health recommendation, it's not only important to critically appraise the evidence on burden of illness and safety and efficacy of an intervention. It's also important to consider issues related to the ethics of a recommendation, equity, feasibility and acceptability of a recommendation. And that's why NACI uses a framework to ensure that these issues are systematically assessed so that we can have recommendations that are comprehensive, that are practical and that are transparent. And that's why NACI also recommended guiding principles for ethical decision making that apply across all the key populations that Caroline outlined. So for example, one of the guiding principles focuses on equity. I mean, I think we can all agree that everyone has been impacted in some way by this pandemic, but there are some who have been disproportionately impacted, and these inequities have certainly been magnified in this pandemic but, you know, they're not new. The virus may be new, but inequities are not new. We know for example, that there are populations who have differences in exposure to infectious diseases, differences in severity and complications of those infectious diseases and also, populations who have different access to health care. And these are all factors that can contribute to health inequities. And if we allocate vaccines inequitably, then we risk exacerbating these unfair inequities. And if we ignore inequities, then we also risk slowing our way out of this pandemic. So NACI recommended that one of the guiding principles for decision making is that efforts should be made to increase access to immunization to reduce health inequities, without any further stigmatization or discrimination. And also, to engage systematically marginalized populations and racialized populations in immunization program planning. You know, we live in a pluralistic society, and respect for all people and all communities, it can really open doors instead of put up walls, so engaging communities is a really important part of this principle. Another guiding principle that NACI unanimously approved is based on acceptability. That efforts should be made to improve knowledge about the benefits of vaccines in general, and of COVID-19 vaccines specifically, once they're authorized and shown to be safe and efficacious. And also to address misinformation about immunization and communicate transparently about COVID-19 vaccines and about decisions on vaccine allocation. And this is one reason why the publication of this guidance in CMAJ that explains the rationale and evidence behind the recommendations is so important. You know, even before this pandemic started, the WHO called vaccine hesitancy, one of the top 10 major global health threats. And we know from surveys in Canada, that willingness to get a safe and effective COVID-19 vaccine has decreased over time. I mean, in this pandemic, we've not only seen the spread of infection, but also the spread of misinformation and disinformation, and it's scary and confusing for people. So, you know, we need to be able to communicate transparently about what we know, and also what we don't know. The third guiding principle speaks to the challenges with feasibly implementing a COVID-19 immunization program. It's not going to be easy, there are a lot of complex issues to work out. So NACI recommends that jurisdictions should begin planning for it. For example, making sure systems are in place for the rapid monitoring of safety, effectiveness and coverage for potentially different vaccines in potentially different key populations.
Diane Kelsall: Those principles are really important, but they sound like they would be a bit of a challenge to implement. What are some of the initiatives or strategies that would help in implementing these principles in COVID-19 immunization programs?
Shainoor Ismail: Absolutely important and absolutely challenging to implement. So to try to help implement these principles, the full guidance document has tools. And these tools have been developed over the last five years with evidence and experience from other vaccine preventable diseases and now we've applied them to COVID. So for example, the equity tool summarizes the evidence for various factors contributing to an inequity. It explores the reasons behind the inequity and then it suggests interventions to try to reduce the inequity and increase access to the vaccine. So as an example, we can look at race or ethnicity. As Caroline mentioned, in the evidence review, this was found to be an independent risk factor for serious outcomes of COVID-19. Now, some racialized populations have differential exposure to the infection, because of occupations and sectors like the food industry, or in health care settings, or because of crowded living conditions, or due to decreased access to health care, or really for a combination of these reasons or other reasons. Now, one strategy to try to address this inequity could be to make sure that vaccines are publicly funded, that they're offered free of charge to these populations in convenient places at convenient hours. And that information about the vaccines is communicated in different languages and different literacy levels by trusted community leaders and advocates, and that the values and preferences of all populations are integrated in vaccine program planning. Now speaking of equity, NACI has also released guidance on research priorities for vaccine clinical trials and in that guidance, NACI recommends that individuals from diverse backgrounds, you know, diverse biological, social and occupational backgrounds, should be included in clinical trial groups. And it's really important to have this evidence on vaccine characteristics in diverse populations, so that equitable and evidence informed recommendations can be made. Now to address the principle of acceptability in NACI's guidance. An important evidence informed strategy is to empower healthcare providers to communicate recommendations transparently and clearly to their patients and also, to empower healthcare providers themselves to make their own informed decisions. They're one of the key populations. So evidence has shown that people are more comfortable getting a vaccine if it's recommended by a healthcare provider. And the evidence also shows that healthcare providers are more comfortable recommending a vaccine if it's recommended by an expert committee, like NACI. So all of NACI's recommendations are available on its web page and the guidance documents transparently summarize all of the evidence that informed the recommendations. So healthcare providers can refer to these documents, as well as the Canadian Immunization Guide, to help them communicate to their patients.
Diane Kelsall: One of the things I think with people listening to this podcast, you've mentioned a number of key populations, and people are probably wondering: "Where am I going to fit in? Am I going to be near the top or I'm going to have to wait?" But the guideline is pretty clear. You don't get into ranking or sequencing these populations. Why is that?
Caroline Quach: Well, that's because this is a preliminary guidance to identify key populations for early COVID-19 immunization, one of the issues we had is that we do not have information on vaccine characteristics like safety and efficacy in different populations at this point in time. This will only come from the late phase clinical trials that are not yet available. The number of doses of vaccines available also is an unknown, and so NACI felt that it was just too early to rank populations to vaccinate. For example, if let's say an authorized vaccine only enrolled in their phase three study healthy participants from 18 to 65 years of age, NACI would feel uncomfortable to use that vaccine in those 70 years or older first, because we wouldn't have any data on either efficacy or safety. And so we then could decide to prioritize healthcare workers to that vaccine instead. It's possible that off-label recommendations will be necessary, but only if supported by a compelling public health ethics analysis. And key populations may change as the evidence base for COVID-19 - whether epidemiology, or transmission dynamics and vaccine characteristics - as already said, immunogenicity, safety, efficacy, effectiveness and preventing severe illness, and interruption of transmission in different populations, as well as information and vaccine supply evolve. And if you look at what the other international groups equivalent to NACI have been doing, you'll also notice that the ones who have attempted to rank have included many caveats about how the ranking is going to change between now and vaccine deployment, as the evidence is evolving so fast. So, some have already ranked and re-ranked their priority groups before the vaccines are even available. And so, we've decided not to do that and really just identify the key populations and continue working on further ranking as data from the vaccines become available.
Diane Kelsall: Do you anticipate that the key populations, I mean the ranking, you'll obviously rank once you get a better idea of vaccine efficacy and other points? Do you anticipate adding any other key populations, or think we have a pretty good idea of who the key population should be?
Caroline Quach: I think we've cast quite a wide net. If ever we see, in terms of epidemiological studies or other clinical studies, that we are missing on a risk population, of course we'll add it in. That's why we're continuously monitoring the literature. And let's say we identify, I don't know, a group based on some genetic test that is more at risk, of course it will come in and that's why you know, we're really keeping our fingers on the pulse here.
Diane Kelsall: Okay. You know, I know Caroline, you alluded to some factors that might influence or change these recommendations. Shainoor, are there any other factors that you think might have an effect?
Shainoor Ismail: NACI recommendations were informed by evidence on a number of factors. And sequencing of the key populations, as well as sub-prioritization within those key populations, will continue to be based on a number of factors. For example, a population-based risk/benefit analysis that takes into consideration things like risk of exposure to the infection, or risk of transmission to others, risk of severe illness and death, as well as the safety and effectiveness of the vaccines in different key populations. Other important factors to consider will be evidence on the vaccine characteristics and the results of clinical trials, the vaccine supply in terms of, you know, the number of available vaccine types, the number and timing of available doses. And of course, the committee will look at the epidemiological context of COVID-19 when the vaccines become available. I mean, the evidence in this pandemic is continually evolving and NACI will be monitoring that evidence, and their guidance will be updated as needed.
Diane Kelsall: You know, I know that everyone wants some good news. And I'm going to ask you to speculate about next year. I hope there's some good news in there, but what do you anticipate next year might look like for us? What can we expect?
Caroline Quach: Well, I think what we're seeing currently is that we're in the midst of the second wave that will last for still a few months. We expect a gradual rollout of vaccines, and that will eventually curve this pandemic, but realizing that this rollout might take a good 12 to 18 months before we are able to vaccinate everybody who needs it. In the meantime, so non-pharmacological interventions like masking and social distancing, will need to be continued. Think when you talk to modelers, they predict that there may be yet another resurgence of COVID-19 in the fall of 2021, and that means that for NACI, the next few months will be busy, the committee will have to review every vaccine that is authorized by Health Canada and decide if one is best suited for certain groups or not. But at least, there is some light at the end of the tunnel. We really hope that the vaccines are going to be efficacious and safe. So far, the phase two data are actually quite encouraging but we're waiting to hear from the phase three data. And so, hard to say exactly what's going to come. I think that like all of, like the rest of Canada, we're all starting to be COVID fatigued. But you know, we're keeping our hopes that something will come and that will be better soon-ish.
Diane Kelsall: There's some good news in there. I think one thing though, you made a really important point, is that it's not going to - and this is the point of this guidance - it's not going to be that suddenly a vaccine is there, everyone gets, you know, gets vaccinated, and then we can stop all of our precautions. It's not going to be that way. This is going to take a while. We don't know whether people are going to need one or two doses. We don't know how efficacious it's going to be. There's a lot of things we don't know but we are glad that groups like NACI are working to provide this kind of information. So I'd like to thank both of you so much for joining me today to discuss this incredibly important topic.
Shainoor Ismail: Thank you, Diane.
Caroline Quach: Well, thank you very much for having us.
Diane Kelsall: I've been speaking with Dr. Shainoor Ismail and Dr. Caroline Quach. To read the guideline they co-authored, visit cmaj.ca. You can also get the full document on the Public Health Agency of Canada's website. Both are linked in the podcast description. Also, don't forget to subscribe to CMAJ podcasts on Soundcloud or a podcast app, and let us know how we're doing by leaving a rating. I'm Dr. Diane Kelsall, consulting editor for CMAJ. Thank you for listening.