Health Committee on March 11th, 2021

[The Chair, Liberal, Ron McKinnon]

I call this meeting to order.

Welcome, everyone, to meeting number 24 of the House of Commons Standing Committee on Health. The committee is meeting today to study the emergency situation facing Canadians in light of the second wave of the COVID-19 pandemic.

I would like to remind everyone that everyone has the right to participate in these proceedings in the official language of their choice. In the event that there is difficulty in hearing translations, please bring it to our attention as soon as possible so that the matter can be resolved.

I would like to welcome the witnesses at this point. From the national advisory committee on immunization, we have Dr. Caroline Quach-Thanh, chair and professor, Université de Montréal. With the Department of Health, we have Dr. Marc Berthiaume, director, health and food branch, therapeutic products directorate, bureau of medical sciences. From the Public Health Agency of Canada, we have Ms. Kimberly Elmslie, vice-president, immunization branch; Dr. Howard Njoo, deputy chief public health officer; and Dr. Guillaume Poliquin, acting scientific director general, national microbiology laboratory.

I would just advise the speakers that I will be using these cards to indicate that your time is almost up. I will typically put up the yellow one about one minute before your time is up. I will use the red one when your time is up, and if you see it, please wrap up in due course.

With that, we will carry on with our presentations. We will start with Dr. Caroline Quach-Thanh.

Doctor, please go ahead for 10 minutes.

[Dr. Caroline Quach-Thanh, Chair, National Advisory Committee on Immunization and Professor, Université de Montréal]

Thank you very much.

Mr. Chair and members of the Standing Committee on Health, thank you for inviting me to speak to you again, this time regarding the use of the AstraZeneca vaccine for adults aged 65 and older.

The recommendations of the National Advisory Committee on Immunization, or NACI, issued on March 1, 2021, were as follows.

A complete and currently authorized COVID-19 vaccine series should be offered to individuals in the authorized age group without contraindications to the vaccine. In the context of a limited vaccine supply, initial doses of the messenger RNA COVID-19 vaccine should be prioritized for the key populations listed in the NACI's “Guidance on the prioritization of initial doses of COVID-19 vaccine(s)” document.

Given the superior efficacy reported in clinical trials, the messenger RNA COVID-19 vaccine is preferentially recommended for individuals in the authorized age group without contraindications, especially for those at highest risk of severe illness and death and at highest risk of exposure to COVID-19.

In the context of a limited vaccine supply, the AstraZeneca COVID-19 vaccine may be offered to individuals aged 18 to 64 without contraindications if the advantages of earlier vaccination outweigh the limitations of vaccinating with a less efficacious vaccine; the ease of transport, storage and handling of this vaccine facilitates access to vaccination that may otherwise be challenging; and informed consent includes a discussion about current vaccine options and the timing of future vaccine options.

At the time the NACI recommendations were made, the committee had assessed the data from the randomized controlled trials submitted by the manufacturer, which meant two phase one/two studies, one phase two/three study, and one phase three study, as well as a real-world effectiveness study performed in Scotland by Vasileiou and colleagues entitled “Effectiveness of first dose of COVID-19 vaccines against hospital admissions in Scotland: national prospective cohort study of 5.4 million people”, which is a preprint. This means it is not yet reviewed by peers.

Data from an ongoing phase three trial in the U.S. are not yet available. Of note, the FDA is waiting on these results to make a decision on authorization. The clinical trials data submitted were challenging to interpret, as there was use of both a low dose/standard dose and a standard dose/standard dose vaccine regimen in trials, a varied interval between doses, and the recruitments of progressively older study participants after the initial focus was put on adults 18 to 55 years old.

The estimates of vaccine efficacy against confirmed COVID-19 cases occurring at least 15 days after dose two, by dosing interval, suggested an increase in vaccine efficacy with an increasing interval between doses of vaccine, but confidence intervals are wide and overlap. As a recap, a 95% confidence interval means that we are 95% confident that the true value—in this case, vaccine efficacy—will fall within these boundaries.

When confidence intervals around a point estimate overlap in a given study, it means that the two estimates could possibly be the same. In this case, the vaccine efficacy with a dosing interval of four to eight weeks was 55.7%, with a 95% confidence interval going from 39% to 68%, while the vaccine efficacy of an interval greater than 12 weeks was 81.6%, with a 95% confidence interval from 47% to 94%, so both intervals are overlapping.

A subgroup analysis of vaccine efficacy against the first occurrence of confirmed COVID-19 at least 15 days after dose two showed that, for all studied intervals between doses, the point estimate for vaccine efficacy ranged around 60% for the younger age group—that means 18 to 64—with a confidence interval that did not include zero. This means a vaccine efficacy is really there, compared with 43% for 65 years and over, with a wide confidence interval that includes zero, meaning that the actual vaccine efficacy could be null.

Based on these data, NACI felt that it was safest, given the availability of two other mRNA vaccines that were highly efficacious in people 65 years and over, to recommend the mRNA vaccines in that age group and not recommend the AstraZeneca vaccine for 65 years and over. This is awaiting further data, including the clinical trial that is ongoing in the U.S.

NACI also reviewed the Scottish paper, as these data were available. This study, which has not yet been peer-reviewed, is a real-time prospective observational cohort with national-level coverage in Scotland, using administrative data that are all linked. The cohort included 5.4 million people. The authors studied the first doses of either the Pfizer-BioNTech or AstraZeneca vaccines. The authors assessed the effectiveness—the effect of the vaccine in real life, as opposed to efficacy, which studies the effect in a randomized clinical trial—against hospital admission with COVID-19 as the main diagnosis within 28 days of a positive PCR for SARS-CoV-2.

During the study period, 35% of participants were vaccinated, mainly among the first priority groups aged 80 years and over. Younger individuals had a higher uptake of the Pfizer vaccine, while those 80 years and over had a higher uptake of the AstraZeneca vaccine. The authors reported a statistically significant adjusted vaccine effectiveness against COVID-19-related admissions in those who received a first dose of either vaccine, which increased over time until a peak at day 28 to day 34 post-vaccination.

Although these data seem promising, the committee was not able to explain why the vaccine effectiveness was so high so early on. On days 7 to 13, the reported effectiveness was already 70%, with a 95% confidence interval from 63% to 76%. This raised questions about the study's methodological validity. Moreover, given the context of the targeted vaccination and study design, NACI considered that there was a high risk of bias and that vaccinated individuals were likely not comparable to unvaccinated individuals. Given these uncertainties, NACI decided that this study was not solid enough to change policy, and kept its recommendation not to use the AstraZeneca vaccine for those aged 65-plus at that point in time.

In the short time since NACI's recommendations were published, two other real-world effectiveness studies have been preprinted. The committee met yesterday, on March 10, to discuss them and decide if these new data would change recommendations. An updated statement, which will include the real-world evidence, will be released as soon as possible.

Regarding Health Canada's authorization, it's important to understand that, while both Health Canada and the National Advisory Committee on Immunization report to the Minister of Health, they don't have a reporting relationship with each other. Health Canada's role is to authorize specific indications for use that are expected to be safe, immunogenic, efficacious, and of suitable quality for individuals. To do so, it reviews preclinical data, clinical trial data, and manufacturing information submitted by manufacturers, along with post-market surveillance data.

Once a vaccine is authorized, the NACI becomes involved. The NACI's role as a technical committee and advisory body is to recommend vaccination strategies to promote health, prevent and control infectious diseases, and prepare for or respond to public health emergencies. The NACI does this by reviewing all relevant and available evidence on the vaccines in question in the context of public health considerations, and then taking into account not only vaccine characteristics and the burden of disease, but also the concepts of ethics, equity, acceptability, and feasibility. The NACI regularly relies on the support of mathematical modellers to assess the effects of various strategies.

The NACI can make off-label recommendations when there's a clear need supported by a public health ethical analysis.

In this particular context, NACI considered the advantages of administering a COVID-19 vaccine earlier to Canadians against the limitations of administering a vaccine that, based on available data, is less efficacious. Based on mathematical modelling, various strategies were studied. In clinical trials, mRNA COVID-19 vaccines demonstrated higher efficacy than the AstraZeneca vaccine. In the context of limited supply, NACI, however, considered additional factors when assessing options for COVID-19 immunization.

Internal modelling reviewed by NACI, based on Canadian supply projections, indicated that a program including both mRNA vaccines and the AstraZeneca COVID-19 vaccine could have short-term public health benefits—preventing symptomatic disease, hospitalization and death—when the AstraZeneca COVID-19 vaccine is offered earlier to adults who are 18 to 54 instead of waiting for an mRNA vaccine, during periods of epidemic transmission. The public health benefits of offering the AstraZeneca vaccine earlier only to individuals who are 55 to 64 years old were less certain, given their shorter expected wait times to get mRNA vaccines. Modelling assumed no impact of vaccines on preventing transmission, as evidence of this is not yet available.

The population that received a lower-efficacy COVID-19 vaccine will have protection against COVID-19 disease earlier than if they had waited for mRNA vaccines to be available. However, these populations may ultimately have lower protection, depending on the duration of protection of both vaccines, as a larger proportion of the population will remain susceptible. Depending on vaccination strategies, it could potentially exacerbate health inequities if this potential harm is not considered when implementing the vaccine program in populations that experience intersecting risk factors for severe disease and exposure.

The mRNA COVID-19 vaccines have more challenging storage and transportation requirements than the AstraZeneca COVID vaccine, which may limit the venues where the vaccine may be offered. Vaccine hesitancy may be reduced by offering the COVID-19 vaccine in more convenient locations. That element was deemed important in the decision as to who should receive the AstraZeneca vaccine.

I hope that this explanation has helped the committee understand the thought process behind the NACI's decisions and recommendations issued on March 1.

Thank you for your attention. I would be happy to answer your questions.

[The Chair, Liberal, Ron McKinnon]

Thank you, Dr. Quach-Thanh.

We will go now to the Department of Health, with Dr. Marc Berthiaume, director, health products and food branch.

Please go ahead, for 10 minutes.

[Dr. Marc Berthiaume, Director, Bureau of Medical Sciences, Therapeutic Products Directorate, Health Products and Food Branch, Department of Health]

Good evening, Mr. Chair.

My name is Dr. Marc Berthiaume, and I am the director of the bureau of medical sciences at Health Canada, health products and food branch.

Thank you for inviting me to appear before the committee today. I appreciate this opportunity to discuss Health Canada's high standards for the vaccine approval process and, in particular, to address questions regarding the approval of the AstraZeneca vaccine for people over 65 years of age.

I want to begin by emphasizing that Health Canada authorizes vaccines only if they meet the department's stringent safety, efficacy and quality requirements.

As with the other vaccines, Health Canada conducted independent and thorough scientific reviews to determine that the benefits outweigh the risks for the AstraZeneca COVID-19 vaccine, which was developed in partnership with Oxford University, as well as the Serum Institute of India's version of the AstraZeneca vaccine, sponsored in Canada by Verity Pharmaceuticals.

Health Canada has rigorously evaluated the data available from clinical trials and real-world evidence, and determined that this vaccine is safe to be administered to adults 18 years of age and older.

We also collaborated with the European Medicines Agency on the review of the AstraZeneca vaccine, as part of its open process. This initiative makes it possible for trusted regulatory authorities outside of the European Union, such as Health Canada, to work together and share information throughout the review process.

All regulatory authorities that have authorized the AstraZeneca vaccine have granted unrestricted adult indications.

Even though limited information from clinical trials is available to calculate its efficacy in people 65 years of age and older, Health Canada's authorization for a broad adult population has taken the available data on immune responses into consideration. There is emerging promising evidence that is beginning to be reported from studies on the real-world use of the vaccine, along with data on the safety profile of the vaccine from millions of people who have received it.

In addition to the encouraging real-world evidence that is already showing benefits with respect to outcomes such as hospitalization, it is important to note that there were no safety issues in this age group. There were no issues in the clinical studies, where about 700 people over the age of 65 were administered the vaccine, nor in the large numbers of seniors who have been vaccinated to date in other countries that have also authorized the AstraZeneca vaccine and are administering it to people over the age of 65.

Specifically, during the first summary of the safety reporting period of January 1-31, 2021, safety data was available for over 3.7 million people who received the vaccine, with no safety issues identified. A safety signal of anaphylaxis has more recently emerged, which is currently being added to the product monograph.

Health Canada is aware of the reports in Europe of adverse events, including fatalities, following immunization with the AstraZeneca vaccine, specifically thromboembolic events such as blood clots. We are monitoring and working closely with national regulators to gather information, including the European Medicines Agency, whose safety committee has initiated an accelerated investigation. At this time, we do not believe this is a new safety issue that will impact the deployment of the vaccine in Canada. These sorts of events demonstrate that our rigorous safety system works well to identify and quickly start to investigate issues.

Health Canada is reassuring Canadians that the benefits of vaccination outweigh the risks. We expect further information from ongoing clinical trials and post-market monitoring in the coming months. If there are additional changes required with regard to safety or efficacy, Health Canada will take the necessary actions.

In the meantime, the department has been transparent regarding the data that was considered, and has reflected the limited data on efficacy for those over the age of 65 in its regulatory document, including the product monograph.

I want to point out that all COVID-19 vaccines were authorized in Canada under an interim order approved in September 2020. This enables us to speed up the review of COVID-19 treatments and vaccines, while maintaining a high level of scientific review.

With this interim order, Health Canada can approve a new vaccine based on available evidence with more agile administrative and application requirements. The interim order also allows for rolling reviews, which lets a vaccine manufacturer submit its request for authorization before it has completed all the clinical trials. This means that it can submit required data as the data becomes available. The interim order also gives Health Canada the authority to impose terms and conditions to require the manufacturer to continue providing information on the safety, efficacy and quality of the vaccine once marketed.

Additionally, we have a strong post-market safety surveillance system to monitor the safety of COVID-19 vaccines. Once a vaccine is on the market, Health Canada and the Public Health Agency of Canada monitor for any adverse events after immunization in collaboration with the provinces and territories and the manufacturer. The interim order provides the authority to impose terms and conditions on any authorization at any time, such as additional assessments of safety information. We'll take swift action if safety concerns are identified.

All Health Canada's regulatory decisions are independent and based solely on scientific data and evidence. Our COVID-19 vaccine review teams are comprised of experienced scientific and regulatory experts, including scientists and physicians with many years of experience in reviewing vaccines. Together, these measures have allowed Health Canada to authorize several clinical trials in Canada for COVID-19 vaccines, as well as for five vaccines: Pfizer-BioNTech, Moderna, AstraZeneca, the AstraZeneca version produced by the Serum Institute in India, and Janssen.

As part of our ongoing commitment to openness and transparency, Health Canada has published detailed information about the authorized COVID-19 vaccines on its COVID-19 vaccines and treatments portal. This information includes Canadian product monographs and regulatory decision summaries that provide a high-level summary of the evidence reviewed to support vaccine authorization.

Health Canada and the Public Health Agency of Canada provide weekly updates on reported adverse events following immunization. Our response to the pandemic is being guided by the latest science and research. We're also continuing to closely monitor the emerging viral variants and to work with manufacturers and international regulators in order to assess the impact of the new variants on vaccine efficacy and provide guidance to manufacturers.

Health Canada, together with the Access Consortium that also includes our regulatory counterparts in the United Kingdom, Australia, Switzerland and Singapore, has developed and published guidelines for the industry regarding our common regulatory approach to authorizing updates to existing vaccines in order to combat new variants.

Canadians can rest assured that the review process for each vaccine has been rigorous and that systems are in place to continue to monitor the safety and efficacy of authorized COVID-19 vaccines. The vaccines play a critical role in Canada's response to the pandemic and fight against COVID-19. The authorization of these additional vaccines, which meet Health Canada's rigorous safety, efficacy and quality standards, provides additional tools to fight this pandemic as quickly as possible.

Thank you.

[The Chair, Liberal, Ron McKinnon]

Thank you, Dr. Berthiaume.

We go now to the Public Health Agency of Canada, which will have collectively 15 minutes to speak. We'll start with Ms. Elmslie, vice-president of the immunization branch.

Ms. Elmslie, please go ahead.

[Kimberly Elmslie, Vice-President, Immunization Branch, Public Health Agency of Canada]

Thank you very much, Mr. Chair. Good evening, members.

This evening I will be speaking about the role of Canada's national advisory committee on immunization in the immunization system in our country. NACI, as you know, is an expert, external body that provides independent advice to the Public Health Agency of Canada on the optimal use of authorized vaccines in Canada. NACI has been operating for over 50 years as the country's national immunization technical advisory group, and it is widely respected by provinces and territories and internationally.

The committee is made up of experts from across Canada in the fields of pediatrics, infectious diseases, immunology, pharmacy, nursing, epidemiology, pharmacoeconomics, social sciences and public health. In the context of COVID-19, Canada's federal, provincial and territorial governments utilize the advice of NACI as the authoritative body on pandemic vaccine prioritization and vaccine public health program design. Its recommendations are designed to support the pandemic public health response goals of reducing serious illness and overall death while minimizing societal disruption as a result of COVID-19.

NACI's COVID-19 advice is focused on the strategic prioritization of vaccines and specific vaccine guidance and ranking of products for clinical use. Its recommendations inform federal, provincial and territorial governments' planning for the efficient, effective and equitable allocation of COVID-19 vaccines. NACI thoroughly reviews available evidence when developing its recommendations. This includes the consideration of vaccine characteristics, such as safety, efficacy, immunogenicity and effectiveness. NACI also incorporates programmatic factors such as economics, ethics, equity, feasibility and acceptability.

NACI's guidance is advisory in nature. Immunization program planning and delivery decisions fall under provincial and territorial jurisdiction. The provinces and territories ultimately determine how to use authorized COVID-19 vaccines based on jurisdictional needs and circumstances, including local epidemiology, public health considerations, health care system capacity and vaccine management logistics.

NACI is supported by a secretariat housed within the Public Health Agency of Canada. While NACI members are not government employees and remain external to the federal government, the secretariat supports committee meetings and deliberations, the rigorous scientific review of evidence and the development of NACI statements and communication products for health care providers and the public. The secretariat support is necessary as the committee members are volunteers, holding important full-time clinical and public health roles.

NACI complements the expertise of its broad membership by conducting extensive stakeholder engagement when developing its recommendations, involving many liaison organizations. The Canadian immunization committee, which is a federal, provincial and territorial table, is actively involved at multiple points in NACI's work. When drafting guidance on COVID-19 vaccines, including the AstraZeneca vaccine, NACI sought input from the special advisory committee on COVID-19, which is made up of provincial and territorial chief medical officers of health and other senior officials.

There is an important distinction to be made between NACI's role and Health Canada's function as Canada's national regulator. It is not uncommon for NACI to provide recommendations that are broader or narrower than the conditions of use approved by Health Canada. NACI is different from Health Canada, which does not dictate practice of medicine or make recommendations on how vaccines should be used in different age groups and subpopulations for public health impact.

In keeping with its mandate to optimize the public health benefits of immunization in Canada, NACI has historically provided preferential recommendations on the use of vaccines in key populations for diseases. Some examples include influenza and shingles vaccines. In making its recommendations, NACI also takes into consideration other vaccines available in Canada and may make preferential recommendations based on the current context. This is different from Health Canada as the regulatory authority that reviews each vaccine independently to assess if there is sufficient evidence of safety, efficacy and manufacturing quality to meet regulatory requirements for authorizations.

Clinicians are very used to consulting both the product monograph and NACI advice when making their clinical vaccine decisions for patients. They do not expect these to be identical, understanding that they are driven by different perspectives.

NACI's recommendations complement regulatory indications with real-world context and with information on public health strategies based on available and evolving evidence. The committee revises its recommendations when needed based on new evidence as well as the evolving context.

On the global stage, other countries rely on their respective national immunization technical advisory groups for COVID-19 expert advice. Through the NACI secretariat within PHAC, NACI is well connected to international advisory committees of this type. In fact, Canada is currently the chair of the global NITAG network, a World Health Organization-supported forum where national technical advisory committees on immunization share information and collaborate on work plans.

The NACI secretariat is in regular contact with countries bilaterally and through the global NITAG network to stay up to date on international COVID-19 developments.

PHAC expects different approaches to be adopted around the world in response to COVID-19. Every country develops immunization programs that are informed by local epidemiology, values, preferences, social infrastructure and health care systems. Naturally, these considerations vary significantly by country.

As you are all aware, real-world evidence on COVID-19 and vaccine effectiveness is evolving in real time. NACI continues to closely monitor and review this emerging evidence and will revise its recommendations as information becomes available.

I would like to thank the committee chair and members for the opportunity to address this committee.

Thank you.

[The Chair, Liberal, Ron McKinnon]

Thank you, Ms. Elmslie.

Is there anyone else from PHAC who wishes to speak?

[Kimberly Elmslie]

There is no one else speaking at this time, Mr. Chair.

[The Chair, Liberal, Ron McKinnon]

Thank you very much.

In that case, we will begin with our questioning.

We will start with Ms. Rempel Garner, please, for six minutes.

[Michelle Rempel, Conservative, Calgary Nose Hill, AB]

Thank you, Chair.

To Dr. Berthiaume from Health Canada, does Health Canada have any concerns that any age group or demographic is at an increased risk of pulmonary embolism or DVT after receiving a dose of the AstraZeneca vaccine?

[Dr. Marc Berthiaume]

There is an ongoing investigation in Europe about thromboembolic events. They are thought to be potentially related to some lots, but more needs to be found.

At this point, there is no concern in Canada about the potential risk for thromboembolic adverse events with the AstraZeneca vaccine. I could add, as a complementary piece of information, that in the U.K., where 11 million doses of the AstraZeneca vaccine were administered, there were no safety signals of thromboembolic events that were identified.

[Michelle Rempel, Conservative, Calgary Nose Hill, AB]

Thank you.

Dr. Quach-Thanh, Dr. Berthiaume spent most of his presentation talking about the safety of the AstraZeneca vaccine, but it's my understanding that your recommendation against using the AstraZeneca vaccine in seniors was related to efficacy. Is that correct?

[Dr. Caroline Quach-Thanh]

You are correct.

[Michelle Rempel, Conservative, Calgary Nose Hill, AB]

Okay.

Do the other vaccines that have been approved in Canada—the two mRNA vaccines as well as Johnson & Johnson—have higher levels of efficacy for age 65 and older?

[Dr. Caroline Quach-Thanh]

If you look at the two mRNA vaccines, the efficacy is actually close to 95% for those aged 65 and over. For Johnson & Johnson, NACI hasn't reviewed all the data, so our recommendation is not out yet, but we do have data on those aged 65 and over that is statistically significant, meaning that the 95% confidence interval does not include zero.

[Michelle Rempel, Conservative, Calgary Nose Hill, AB]

Okay.

In your comments, you talked about making decisions within the context of limited supply. Do you think that the lack of vaccine supply in Canada to date, coupled with the threat of variants, played into the government's decision to approve the AstraZeneca vaccine for those aged 65 and older in spite of your recommendation?

[Dr. Caroline Quach-Thanh]

I think you would have to ask Health Canada for the exact reasons.

[Michelle Rempel, Conservative, Calgary Nose Hill, AB]

Certainly.

Dr. Berthiaume, I'll ask you the same question. Did the lack of supply or limited supply of mRNA vaccines play into your decision to ignore NACI's advice?

[Dr. Marc Berthiaume]

No, it did not. Health Canada based its decision on a number of elements. There was evidence of immunogenicity—that people over 65 in immunogenicity studies were building antibodies when administered this vaccine. The paucity of the data is related to the small number of people who were in clinical trials who were 65 and over, and that's reflected in the product monograph—

[Michelle Rempel, Conservative, Calgary Nose Hill, AB]

But all else considered equal, what we've just heard is that the mRNA vaccines are significantly more effective for ages 65 and over than AstraZeneca is, so why did Health Canada not recommend prioritizing the Pfizer vaccines for that age group and AstraZeneca for other age groups, in which it would have a higher level of efficacy?

[Dr. Marc Berthiaume]

If you make a comparison, for example, with antibiotics for pneumonia, Health Canada would approve a set of antibiotics for pneumonia but would not necessarily say “this one is better than this one.” Then it would come down to the practice guidelines of different experts to guide the clinical decision-making.

[Michelle Rempel, Conservative, Calgary Nose Hill, AB]

But in this case, with limited supply and the economy in lockdown and the variants obviously being a threat, wouldn't Health Canada be well advised to consider the most vulnerable population when recommending prioritization of vaccines?

[Dr. Marc Berthiaume]

Health Canada's strategy is to have a portfolio of vaccines that offer different characteristics. For example, the AstraZeneca vaccine has one characteristic that's very interesting, which the others don't have, and that is that the vial, once you take the first dose, can be refrigerated and used for other patients for up to 48 hours, while all three others are only for six hours—

[Michelle Rempel, Conservative, Calgary Nose Hill, AB]

But—

[Dr. Marc Berthiaume]

Let me finish, please.