It’s generally agreed that healthcare workers should be first in line for COVID-19 vaccines. Who comes next, however, may depend on whether the goal is to prevent infections or deaths, according to a presentation at the CDC’s Advisory Committee on Immunization Practices (ACIP) on Friday.
A modeling study found that prioritizing adults ages 65 and older would avert more COVID-19 deaths, but prioritizing adults with high-risk medical conditions and essential workers would avert more COVID-19 infections, said Matthew Biggerstaff, ScD, of the CDC.
“Timing of the campaign is a really important factor in the potential impact of the vaccine,” he said at the ACIP meeting dedicated to COVID-19, describing three scenarios when the vaccine is distributed: before incidence rises, as incidence rises, or as incidence falls.
Not only that, but the type of vaccine plays a role, whether infection-blocking, meaning it will help stop transmission of the virus, or disease-blocking, meaning it will help reduce severity of illness, but have no bearing on whether people get infected.
ACIP will be responsible for ultimately deciding which populations receive the vaccine once the FDA approves a COVID-19 vaccine, likely under emergency use authorization (EUA). Previous proposals stated that healthcare workers would be vaccinated in in phase 1a, while phase 1b would take in essential workers” and adults ages 65 and older and those with high-risk medical conditions such as COPD, heart disease, diabetes and kidney disease.
Biggerstaff explained that his group’s models assumed 180 million initial doses of vaccine would be available, with 20 million of those allocated to healthcare personnel. Each modeling scenario then looked at two-dose vaccine courses allocated exclusively to each one of the phase 1b populations, followed by wider availability to the unvaccinated groups in each scenario.
They assumed a vaccine efficacy of 70%, with the first dose at a quarter of full protection, or 17.5%. Protection was assumed 14 days following vaccination. (Notably, though, the FDA has said it will consider vaccines with efficacy as low as 50%.)
The models assumed 15% of the population was infected 2 months prior to vaccine introduction and examined infections and deaths averted 6 months following vaccine introduction.
In this case, earlier introduction of vaccine was better in all scenarios, with vaccine introduced “before incidence rises” having the greatest impact.
The model with the greatest impact on infection was an infection-blocking vaccine, where vaccinating high-risk adults averted about 5% more cases of infection than vaccinating adults age 65 and older in a scenario before disease incidence rises.
However, an infection-blocking vaccine where older adults were vaccinated first averted about 4% more deaths than vaccinating high-risk adults first. This assumed full protection from the vaccine, there was no difference when the vaccine only provided older adults half protection.
A sensitivity analysis examined a disease-blocking vaccine where older adults were vaccinated first, in a scenario where a vaccine is introduced before incidence rises, would avert 11% more deaths.
Expanded Access Versus EUA
Doran Fink, MD, PhD, of FDA’s Office of Vaccines Research and Review, updated ACIP about the Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting on Oct. 22, and the committee seized on an issue that came up for the FDA panel near the end of the discussion: using expanded access protocols versus EUA for a COVID-19 vaccine.
When asked if there were examples of vaccines being provided under expanded access protocols, Fink offered two: a meningococcal serogroup B (MenB) vaccine given to college students following an outbreak, prior to the licensure of a MenB vaccine; and “more recently,” offering Stamaril, a yellow fever vaccine not approved in the U.S., in the face of a shortage of YF-Vax in the U.S.
Fink emphasized FDA was still in the early stages of “determining if this would be an appropriate measure that would be considered.” If a vaccine manufacturer had an active investigational new drug application on file with the agency, they could theoretically submit a protocol for use of vaccine under expanded access regulations and would work potentially with other government agencies “to organize and implement expanded access protocol,” he said.
An expanded access protocol would also not be appropriate for certain populations in the absence of data, such as pediatric populations, Fink noted.
When asked about the median 2 months of safety data, Fink confirmed this meant at least half of subjects will have 2 months of follow-up, but said “a high proportion of enrolled subjects will have at least 1 month of follow-up.” He stressed that it may be impractical to demand longer follow-up “especially in the face of very convincing efficacy data.”
Once the VRBPAC makes a recommendation about an EUA or approval, FDA review will be done “expediently,” Fink said, but he couldn’t say “how many days or weeks” afterwards.