BARELY WEEKS AFTER THE APPROVAL OF COVID VACCINES, OFFICIALS ARE TOYING WITH THE IDEA OF ADJUSTING DOSING SCHEDULES TO EKE OUT SUPPLIES, A GAMBLE THAT COULD LEAVE PEOPLE ONLY PARTIALLY IMMUNE.
Experts wrestle with stretching limited vaccines
Barely weeks after the approval of COVID-19 vaccines, officials are toying with the idea of adjusting dosing schedules to eke out supplies, a gamble that could leave people only partially immune and wobble confidence in an already shaky vaccine rollout.
With provincial premiers warning of dwindling supplies and being forced to work with a “squirt gun” rather than a fire hose, as Manitoba's Brian Pallister said this week, Canada's Chief Public Health Officer Dr. Theresa Tam this week revealed the topic of “making adjustments in the face of constrained supplies” is actively being discussed.
Both vaccines approved so far — Pfizer-BioNTech and Moderna shots — require two doses, 21 days (Pfizer) and 28 days (Moderna) apart. Tam is seeking advice from the country's immunization advisory committee about what is known, and what isn't, about stretching out the interval between doses.
It's not about not ultimately giving people two doses, Tam said, stressing Canada is committed to a two-dose regimen. While available data on how effective vaccines are after that first dose “does look promising,” it's limited, she said.
Already, Ontario, Quebec and other provinces are no longer holding back half of the doses required for the second jab with each delivery, counting instead on the supply chain to produce the second doses in time. British Columbia this week announced second doses would be administered approximately 35 days after the first in order to “maximize the number of priority populations to receive the first dose.” Quebec residents who have already received the first shot have also been told they' ll have to wait longer than expected for the second.
In the United States, officials are exploring administering half-doses of Moderna's vaccine to people aged 18 to 55. Britain said it will stretch out the time between shots to as long as three months, “effectively turning that country into a living laboratory,” according to STAT news.
Canada's vaccine advisory group has said Moderna and Pfizer vaccines, which share similar technology, can, if authorities are hard pressed, be interchanged. “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,” the group's chair, Dr. Caroline Quach, told the Canadian Medical Association Journal.
Mixing, halving, delaying. With infections surging and a new super-infectious strain sweeping the U.K., all may be reasonable options to consider, some experts say: Getting more people vaccinated as quickly as possible provides some level of protection from severe disease across a wider swath of the population.
But not only is it a gamble — will those second doses come in as expected, and how much space can you safely leave between shots? — there's no science yet to support a change.
“The available data continue to support the use of two specified doses of each authorized vaccine at specified intervals,” the U.S. Food and Drug Administration said in a statement this week. 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,” the FDA commissioners said.
Federal officials this week said Canada is on track to have more than 1.2 million doses of Pfizer and Moderna delivered by end of January, and that the government is working “diligently” to secure a predictable flow of vaccines. But Ontario Premier Doug Ford said the province will run out of its next shipment of Pfizer shots by next week and that the province is getting only a day or two of notice before shipments arrive.
Pfi z er Canada hasn' t changed its recommendation that half the doses sent to provinces be held back to be used as second doses. The safety and efficacy trials were based on a particular schedule and a particular dose, and the majority of volunteers got the second jab “within the window specified in the study design,” Pfizer's Christina Antoniou told the Montreal Gazette.
Messaging is key here, said McGill University bioethicist Jonathan Kimmelman. “People may not appreciate that a vaccine proven to be 90 to 95 per cent effective may be considerably less effective if it's not deployed according to the regimen that was validated in the clinical trial,” he said. By sending a message that it's safe to wait longer between doses, people may walk out of clinics after the first jab and think they're completely immune.
It's always good to scrutinize the evidence, Kimmelman said. “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,” Kimmelman said. “And we don't have very firm or solid evidence that deviating will be as protective.”
On the other hand, under a steady vaccine supply, “storing vaccines versus getting them in arms doesn't make a lot of sense,” said University of Toronto epidemiologist Ashleigh Tuite. In a modelling study published this week in Annals of Internal Medicine, Tuite and colleagues estimate that between 20 and 30 per cent more infections could be averted by withholding fewer doses during early distribution, compared to freezing half of each vaccine instalment as insurance against a total collapse in supply (though all second doses were administered on schedule, within three weeks of the first, in both strategies.)
“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,” Tuite said.
A bit of a delay isn't a problem, she said. Beyond a week or two, “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,” Tuite said. Vaccine hesitancy is already an issue. “I think we run the risk of trying things in the population without having a lot of strong evidence to do it.”
In the Moderna and Pfizer trials, a small number of volunteers received just one dose. In the Pfizer trial, there was 52 per cent efficacy in the first three weeks after the first dose; the Moderna trial found roughly 80 per cent efficacy at four weeks.
The second dose provides a dramatic boost in immune response — “much closer, and arguably better than that found with natural infection,” said Dr. Paul Offit, a professor of pediatrics at Children's Hospital of Philadelphia and member of the U.S. FDA's advisory committee evaluating COVID-19 vaccines.
It's not known, from the original trials, how long the first dose is effective, beyond those first few weeks, he said. “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,” Offit said. “That should be the effort. That should be the discussion.”
STORING VACCINES VERSUS GETTING THEM IN ARMS DOESN'T MAKE A LOT OF SENSE.