Canada: An Official Strong Recommendation for First Doses First

By Alex Tabarrok

Canada’s National Advisory Committee on Immunization (NACI), a scientific advisory group to the government, has made a forceful and dramatic statement strongly favoring First Doses First (delay the second dose.) This is a very big deal for the entire world. Basically NACI have endorsed everything that Tyler and I have said on First Doses First since my first post tentatively raised the issue on December 8. I am going to quote this statement extensively since it’s an excellent summary. No indentation.

—-NACI Statement—-

Based on emerging evidence of the protection provided by the first dose of a two dose series for COVID-19 vaccines currently authorized in Canada, NACI recommends that in the context of limited COVID-19 vaccine supply jurisdictions should maximize the number of individuals benefiting from the first dose of vaccine by extending the second dose of COVID-19 vaccine up to four months after the first. NACI will continue to monitor the evidence on effectiveness of an extended dose interval and will adjust recommendations as needed. (Strong NACI Recommendation)

    • In addition to emerging population-based data, this recommendation is based on expert opinion and the public health principles of equity, ethics, accessibility, feasibility, immunological vaccine principles, and the perspective that, within a global pandemic setting, reducing the risk of severe disease outcomes at the population-level will have the greatest impact. Current evidence suggests high vaccine effectiveness against symptomatic disease and hospitalization for several weeks after the first dose, including among older populations.

Protecting individuals

  • By implementing an extended four month interval strategy, Canada will be able to provide access to first doses of highly efficacious vaccines to more individuals earlier which is expected to increase health equity faster. Canada has secured enough vaccines to ensure that a second dose will be available to every adult.
  • As a general vaccination principle, interruption of a vaccine series resulting in an extended interval between doses does not require restarting the vaccine series. Principles of immunology, vaccine science, and historical examples demonstrate that delays between doses do not result in a reduction in final antibody concentrations nor a reduction in durability of memory response for most multi-dose products.
  • Assessment of available data on efficacy and effectiveness of a single dose of mRNA vaccine was a critical factor in assessing the impact of a delayed second dose at this time. The two available clinical trials for mRNA vaccines (Pfizer-BioNTech and Moderna) provide evidence that indicates that efficacy against symptomatic disease begins as early as 12 to 14 days after the first dose of the mRNA vaccine. Excluding the first 14 days before vaccines are expected to offer protection, both vaccines showed an efficacy of 92% up until the second dose (most second doses were administered at 19-42 days in the trials). Recently, real world vaccine effectiveness data presented to or reviewed by NACI assessing PCR-positive COVID-19 disease and/or infection from Quebec, British Columbia, Israel, the United Kingdom and the United States support good effectiveness (generally 70-80%, depending on the methodology used and outcomes assessed) from a single dose of mRNA vaccines (for up to two months in some studies). While studies have not yet collected four months of data on effectiveness of the first dose, the first two months of population-based effectiveness data are showing sustained and high levels of protection. These data include studies in health care workers, long term care residents, elderly populations and the general public. While this is somewhat lower than the efficacy demonstrated after one dose in clinical trials, it is important to note that vaccine effectiveness in a general population setting is typically lower than efficacy from the controlled setting of a clinical trial, and this is expected to be the case after series completion as well.
  • Published data from the AstraZeneca clinical trial indicated that delaying the second dose to ≥ 12 weeks resulted in a better efficacy against symptomatic disease compared to shorter intervals between doses.
  • The duration of protection from one or two doses of COVID-19 vaccines is currently unknown. Experience with other multi-dose vaccines after a single dose suggests persistent protection could last for six months or longer in adolescents and adults. Longer-term follow-up of clinical trial participants and those receiving vaccination in public programs will assist in determining the duration of protection following both one and two doses of vaccination. NACI will continue to monitor the evidence on effectiveness of an extended interval, which is currently being collected weekly in some Canadian jurisdictions, and will adjust recommendations as needed if concerns emerge about waning protection.

Protecting populations

  • Although effectiveness after two-doses will be somewhat higher than with one dose, many more people will benefit from immunization when extending the interval between doses in times of vaccine shortage; offering more individuals direct benefit and also the possibility of indirect benefit from increasing population immunity to COVID-19 disease. Everyone is expected to obtain the full benefit of two doses when the second dose is offered after 4 months.
  • Internal PHAC modelling reviewed by NACI based on Canadian supply projections suggested that accelerating vaccine coverage by extending dose intervals of mRNA vaccines could have short-term public health benefits in preventing symptomatic disease, hospitalizations, and deaths while vaccine supply is constrained. Even a theoretical scenario analysis in which intervals were extended up to six months and protection was lost at a rate of 4% per week after the first dose also showed that extending the mRNA vaccine dose intervals would still have public health benefits. External modelling results have also suggested that extending dose intervals can avert infections, hospitalizations and deaths.
  • The impact on variants of concern by extending the interval between doses is unknown, but there is currently no evidence that an extended interval between doses will either increase or decrease the emergence of variants of concern. COVID-19 mRNA vaccines and AstraZeneca vaccine have shown promising early results against variant B.1.1.7. As effectiveness of the first dose against other variants of concern is emerging, ongoing monitoring will be required.
  • Vaccine distribution will be optimized through this strategy, and current vaccine supply projections will work well with an extended dose strategy that aims to immunize as many Canadians as efficiently as possible. Extending the dose intervals for mRNA vaccines up to four months has the potential to result in rapid immunization and protection of a large proportion of the Canadian population….