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.