A Slow Start To COVID-19 Vaccines Has The FDA Facing Calls To Change Shot Schedules
By cutting doses in half or delaying second shots, some scientists say we could maximize the number of people who get vaccinated. Others argue that could be dangerous.
Facing a slow vaccine rollout, surging COVID-19 deaths, and the threat of a dangerous variant of the virus spreading nationwide, some scientists are calling for vaccine doses to be cut in half or delayed in an urgent effort to quickly get shots to as many people as possible. But other scientists and US regulators are pushing back, worried that this change of plan might have disastrous consequences.
The burgeoning disagreement pits experts against experts, just as the first Americans to be given COVID-19 vaccines start to receive their second shots.
Nobody knows for sure how effective a single dose will be, or for how long, given that clinical trials were set up to test a two-dose schedule. And worse, there are fears that giving people only partial protection could increase the chance of the virus evolving to resist the effects of the vaccines.
Still, some scientists say the circumstances call for extraordinary measures. “When it comes to COVID-19, we’re being punched in the mouth over and over again. It’s time to change the plan,” wrote Ashish Jha of Brown University and Bob Wachter of the University of California, San Francisco, in a Washington Post editorial on Sunday, calling for the vaccine to be given to as many people as possible and delaying second shots until more doses are made.
Food and Drug Administration chief Stephen Hahn and agency vaccine center director Peter Marks rebuffed any changes to the current plan in a statement released on Monday evening, saying, “at this time, suggesting changes to the FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence.”
Two vaccines, one made by Pfizer and the other by Moderna, were authorized last month for emergency use in the US. Large-scale clinical trials found two doses were highly protective for months against COVID-19 when given three or four weeks apart. Signs of reduced COVID-19 diagnoses among study participants seen in between the two doses don’t justify changing that schedule, said the FDA’s Hahn and Marks. The Infectious Diseases Society of America supported the FDA statement on Tuesday, calling schedule changes “premature and potentially harmful.”
“The clinical trials were designed to give two doses on a schedule for a reason. That’s the data we have,” said University of California, San Francisco, vaccine expert Joel Ernst. “I think the agency [FDA] is injecting a dose of operational reality into an interesting and useful scientific discussion, one that we should also be having.”
The United Kingdom’s Joint Committee on Vaccination and Immunisation (JCVI) jolted the debate forward last week by stretching out the timing for a second dose of Pfizer’s vaccine to as long as three months, at a time when 1 in 30 Londoners is thought to be infected with the coronavirus. Most strikingly, the committee suggested that in emergencies, a second dose of a different vaccine might be used if the one from the first shot wasn’t available, or if it was unknown which vaccine was first administered. The British Society for Immunology reluctantly supported the timing change, citing the evidence that a more highly transmissible variant of the pandemic coronavirus is behind a staggering upsurge in cases there.
"What is going on in the UK is reflecting an urgent situation there," said University of Florida biostatistician Natalie Dean. "I can't see the US making that sort of change without the transparent process at FDA and CDC that led to the authorization of the vaccines in the first place."
The B.1.1.7 coronavirus variant, first identified in the UK, complicates calculations of how many people need vaccination, because it is more transmissible. Now seen in more than 30 countries, “in the US, we have to assume that variant is probably all over,” said Dean. Though it has so far only been detected in four states, poor genomic surveillance in the US likely means it’s more prevalent than we currently know. Even if it’s widespread, that shouldn’t change the math right now for sticking to current vaccine schedules, Dean said.
In the coming months, we’ll know better from the vaccines the antibodies and immune system cells that deliver protection from infection, she added. “Once we have these correlates of protection, then we can be more confident about any changes in dosing.”
Pfizer and Moderna both sent BuzzFeed News statements on Monday supporting the second-dose schedule the FDA had authorized. “While decisions on alternative dosing regimens reside with health authorities, Pfizer believes it is critical to conduct surveillance efforts on any alternative schedules implemented and to ensure each recipient is afforded the maximum possible protection, which means immunization with two doses of the vaccine,” said the Pfizer statement. A World Health Organization expert panel on Tuesday backed Pfizer’s schedule, but said in exceptional circumstances, the second dose could be given up to six weeks later.
In the US, meanwhile, Operation Warp Speed's chief scientist Moncef Slaoui raised the idea on Sunday of giving people two half-doses of the Moderna vaccine to stretch supplies. The US National Institutes of Health confirmed the half-dose idea was under study on Tuesday, the New York Times reported. That Slaoui suggested stretching the supply, however, struck some experts as surprising, as his $18 billion vaccine private-public partnership, widely celebrated for quickly spurring the development of vaccines, has come under fire for falling short of its promise to have 20 million shots given by the end of the year. They only delivered 17 million, and shots have been administered to just over 5 million people as of Wednesday.
Some public health figures, such as Jha and Wachter, have called for the US to join the UK in stretching out timing of second shots. But in its Monday night statement, the FDA suggested this line of argument overstated how much certainty there was of effectiveness after one shot.
“We have to recognize that every vaccine is different, and we don’t know everything,” said Ernst, calling for caution. “If we knew everything, we would have had an HIV vaccine 30 years ago.”
For pandemic modeler Marc Lipsitch of Harvard’s T.H. Chan School of Public Health, the FDA’s position reflects its role as the US gatekeeper of new treatments.
“The FDA is a regulator. They’re not, in the broad sense, a public health agency — their job is to make sure that the things that we inject into ourselves and take as pills and supplements and whatever do what they are advertised as doing. And in that narrow sense, they’re right,” he said at a Tuesday briefing.
“It’s a really interesting case where science as regulators see it, and science as public health in the broader sense sees it, might be sort of different,” Lipsitch said.
The other main concern that many experts have with suggestions to change the schedule of US doses is that states can't seem to inject the doses already shipped out. Vaccine rollout overall has been slower than advertised, with big variation from state to state.
“This is basically spiking the ball at the 1-yard line,” said virologist Angela Rasmussen of the Georgetown Center for Global Health Science and Security. “Why are we talking about fundamentally tinkering with proven efficacious dosing regimens when — I get we have a limited supply of vaccines — when we are not able to get the supply that we have into people’s arms?”
Vaccine projections have steadily eroded for months this way, starting with OWS downgrading initial promises of 300 million doses by January, a projection quietly abandoned in August.
“They are behind, by their own projections, they are behind,” said Georges Benjamin, executive director of the American Public Health Association. “The truth of the matter is we always expected some shake out, these are complicated vaccines. But all of this pointing to us needing to move to a much more rapid pace of administering shots.”
With the billions added in a recently passed spending bill, and future ones called for by the incoming Biden administration, the US needs to move to administering 2 million to 3 million vaccine shots a day, Benjamin added, to turn the tide on the pandemic. Arguing about dosing schedules instead of enrolling retired doctors, dentists, and anyone else who can give a shot to get out doses parked on shelves right now is beside the point.
“What is the goal? The goal is to stop the pandemic. We need to use all the tools we have to stop the pandemic.”
The failure of the US Senate to appropriate vaccine rollout money to states until last week — along with storms and a holiday season — hampered vaccine rollouts in medical facilities already handling heavy COVID-19 case numbers, Jim Blumenstock of the Association of State and Territorial Health Officers told BuzzFeed News. “At the end of the day, our fractured healthcare system makes all this much more difficult,” he said. “The federal government needs a much stronger role.”
The first stage of the vaccine rollout, held in large medical centers and nursing homes, is not where most of the vaccinations are supposed to take place months from now. Late on Tuesday, the Trump administration said it was accelerating a plan to start giving vaccine shots in pharmacies. The eventual plan is to follow how flu shots are given, with doctor’s offices, pediatricians, and pharmacies providing immunizations. So far this season, some 71 million flu shots have been given to US adults in 15 weeks, with more than 8 million shots given in some weeks, after low numbers to start. In the fall, the CDC’s Amanda Cohn warned members of its vaccine advisory panel that the first six weeks of the COVID-19 vaccine rollout would likewise be marked by small numbers of shots before ramping up.
“If we look again in three weeks, our conversation about vaccines might be a different one,” said Blumenstock. OWS’s Slaoui has compared the COVID-19 vaccination campaign to the yearly flu one, scaled up by a factor of three to four.
But that sounds optimistic, Emory University’s Walter Orenstein, former director of the US National Immunization Program, told BuzzFeed News. Flu vaccinations, where people know what they are getting, is a lot easier than COVID-19 vaccinations, he said. Flu shots are just one shot, without the varied cold chain requirements, more involved consent requirements, and booster scheduling, seen with the COVID-19 vaccines we have now. “We never did have a situation like this one,” Orenstein said, even compared to the rushed rollout of an H1N1 flu vaccine in 2009. “Vaccines don’t give themselves. The big issue here will be getting people to work together.”
The real threat from both shortfalls in shot projections and talk of upending vaccine schedules is that public trust in vaccines could decline, said health communication expert Michelle Driedger of the University of Manitoba in Canada. In focus groups this year, she has found a lot of apprehension around taking new vaccines. Canada’s rollout is run like the US one, with the federal government distributing doses to provinces, which decide how to allocate their shots.
“I think the FDA’s statement was very clear and effective, an excellent public health message,” she said. “I think at the public level we need to have that understanding that agencies are doing their due diligence.”
Stephanie M. Lee contributed reporting to this story.
Correction: Angela Rasmussen is at the Georgetown Center for Global Health Science and Security. An earlier version of this post misstated her institution.