Changing Horses In Midstream

"Let's say you run out of Pfizer's vaccine because you've administered all your doses, or you don't know what your patient had at first ... this eases up the complexity."

Dr.Caroline Quach, chair, Canada's vaccine advisory group

 

"The available data continue to support the use of two specified doses of each authorized vaccine at specified intervals."

"[Deviate, without supporting data, and] we run a significant risk of placing public health at risk, undermining the historical vaccination efforts to protect the population from COVID-19."

U.S.Food and Drug Administration commissioners

 

"People may not appreciate that a vaccine proven to be 90 to 95 percent effective may be considerably less effective if it's not deployed according to the regimen that was validated in the clinical trial."

"It's possible that if you look deeply at the clinical trial evidence ... that you may find some evidence to support a deviation from those dose schedules."

"[But when deploying a massive intervention], you want to go with the best evidence you have available. And we don't have very firm or solid evidence that deviating will be as protective."

Jonathan Kimnmelman, bioethicist, McGill University

Lailamie Viloria, 48, a personal support worker at Fudger House Long Term Care home in Toronto receives a COVID-19 vaccine at St. Michael's Hospital in Toronto, Dec. 22, 2020.  Melissa Tait/The Globe and Mail

"[Under a steady vaccine supply], storing vaccines versus getting them in arms doesn't make a lot of sense."

"The idea wasn't to say that we should delay the second dose. It was much more about, if you have doses in hand, get them in arms and trust the vaccine supply chain."

"[Beyond a week or two delay] that's where you start getting into uncharted territory."

"There's a good chance that we go off label [using a vaccine in unapproved ways], and it's fine, but there's also the risk that delaying those second doses has unintended consequences."

"I think we run the risk of trying things in the population without having a lot of strong evidence to do it."

Ashleigh Tuite, epidemiologist, University of Toronto

Canada’s COVID-19 vaccine rollout has gotten off to a sluggish start, but there could be lessons to learn from countries such as Israel, which has vaccination clinics operating around the clock

No sooner have several weeks passed since the authorization granted for the new COVID-19 vaccines than a new field of conjecture has arisen with authorities considering the feasibility of adjusting dosing schedules in an effort to string out available supplies to reach as many people to protect against the coronavirus as possible. There are many uncertainties, and among them an outcome that might have the potential of leaving people with only partially immune status, and in the end create a situation where people already suspicious of the efficacy of a 'rushed' vaccine find fresh fuel for dissent. 

Provincial premiers have so far used only a portion -- in some instances, a mere quarter -- of the vaccine doses supplied to them by the federal government as they begin to roll in, maintaining the bulk in freezers rather than rolling it all out and jabbing arms, but they're warning of dwindling supplies, being forced to work around inadequate guidelines. Theresa Tam, the country's Chief Public Health Officer floated "making adjustments in the face of constrained supplies", in active discussion.

Pfizer-BioNTech and Moderna both require two doses, spaced 21 days apart for Pfizer and 28 days for Moderna and Dr.Tam invites advice from the immunization advisory committee to clarify what is known and what remains unknown relating to the possibility of stretching the intervals between doses. Canada, Dr.Tam stressed, is committed to a two-dose regimen; the question at hand is not providing two doses, but rather covering as many options as possible.

Data available on how effectively vaccines can be relied upon with only the initial dose "does look promising", but it's limited. Ontario, Quebec and other provinces no longer retain half the doses required to administer the second dose with each delivery; instead relying on the supply chain to produce the second doses in reasonable time. British Columbia has decided that second doses would be given 35 days following the first to "maximize the number of priority populations to receive the first dose", while Quebec residents for whom the first shot has been delivered have been informed their second dose will  take longer than anticipated.

And it is not just Canada desperate to find new initiatives whereby the vaccine doses in hand thus far secured can go a little further. It started when the pharmaceutical companies cautioned that vial 'leftovers' can be retained for use rather than discarded once the requisite number of doses has been extracted from a vial. Now, in the United States, officials are looking into the possibility of admiinstering half-doses of Moderna's vaccine to those in the 18 to 55 age bracket. While Britain plans to stretch out the time lapsed between shots up to three months "effectively turning that country into a living laboratory".

Moderna and Pfizer vaccines, sharing similar biotechnology are able, should authorities feel hard pressed, to be interchanged, according to Canada's vaccine advisory group. Looming on the near horizon are initiatives such as mixing, halving, delaying; all in response to surging infections and the emergence of a new super-infectious mutation replacing the original COVID virus in the United Kingdon. Expert opinion is that all these initiatives may be considered reasonable options under consideration to ensure that greater numbers of people are vaccinated quickly to provide a level of protection from severe disease.

Enter cautionary advice; these initiatives represent questionable gambles with no assurance that those second doses will arrive as anticipated, let alone the time range that can be safely used between shots, with no science to support such changes as yet. According to federal officials Canada is expected to count over 1.2 million doses of Pfizer and Moderna to be delivered by January's end. Not according to Ontario's premier, warning that the next shipment of Pfizer shots will be quickly absorbed leaving the province with uncertainty over future deliveries.

Moreover, Pfizer Canada reminds that its recommendation stands, that half the doses received by provinces should be held back for use as second doses since the safety and efficacy trials were based on this precise schedule and dosage and the majority of volunteers received their second dose "within the window specified in the study design". According to a modelling study published in the Annals of Internal Medicine by Dr.Tuite and colleagues, between 20 and 30 percent more infections could be averted through withholding fewer doses during early distribution in comparison to freezing half of each vaccine installment.

Paramedics transport a resident from Midland Gardens Care Community in Toronto on Jan. 5. (Evan Mitsui/CBC)

"[The second dose provides a dramatic boost in immune response]; much closer, and arguably better than that found with natural infection."

"And if you disrupt the schedule by saying, 'look, we'll give you the second dose when we can', a lot of people aren't going to get the second dose."

"More importantly, a lot of people, having gotten only one dose, will think that they're, at some level, protected when they may not be protected at all after two or three or four months."

"We have vaccines, remarkably, within a year of identifying and sequencing this virus."

:Our job now is to mass produce them and figure out a way to distribute and administer them That should be the effort. That should be the discussion."

Dr.Paul Offit, professor of pediatrics, Children's Hospital of Philadelphia, member, U.S. FDA advisory committee evaluating COVID-19 vaccines