FDA DEBATES USE OF ‘EMERGENCY’ VACCINE
Urgency grows as U.S. records the highest single-day number of cases Friday
Within months, healthy Americans could be offered an unlicensed vaccine that has not yet completed rigorous study — and the immense implications are slowly becoming clear.
Confronted by the growing coronavirus pandemic, the U.S. Food and Drug Administration is debating the historic use of “emergency use authorization” to permit the use of vaccines when only preliminary — and incomplete — data shows evidence of safety and efficacy.
And the urgency grows as the nation reached a dismal new milestone on Friday, with more than 79,000 new cases reported, 3,000 more than the single- day record set on July 16.
In a Thursday meeting, the FDA insisted that it will enlist “unwavering regulatory safeguards” and not cut any corners if it allowed the early deployment of an experimental COVID-19 vaccine.
But scientific advisers at the marathon meeting warned that the rapid timetable could jeopardize critical research and damage public confidence in a vaccine. And with such limited data, they added, there may not be enough evidence to prove that a vaccine protects people at highest risk, such as the elderly and members of minority groups.
“There’s only one chance to do this,” said
Sheldon Toubman, a Connecticut lawyer and the consumer representative for the FDA’s Vaccines and Related Biological Products Advisory Committee. “If we do it wrong, then we’re done for.”
The debate comes as two vaccines, made by Pfizer and Moderna, are in the final stage of testing. Trials of the other two leading candidates, by AstraZeneca and Johnson & Johnson, have been suspended because of possible side effects.
If granted, such permission would be unprecedented. Only once before has the FDA authorized the emergency use of a vaccine. And that application — to prevent anthrax poisoning in members of the military — was very narrow.
Adding to the unease is the new design of the Pfizer and Moderna vaccines. They use the power of genetics to produce their vaccines, enlisting a “messenger RNA,” or mRNA, technology. While promising, it has never before received regulatory review.
Because this approach has been proven safe in other applications, the main worry is over efficacy: It’s hard to get it to do precisely what you want it to do.
New poll results released Wednesday by the Public Policy Institute of California show that two-thirds of Californians surveyed are concerned about a rushed approval process for a COVID-19 vaccine. There was particular distrust among Black respondents, with only
29% saying they would definitely or probably get vaccinations, compared to 70% of Asian Americans, 62% of whites and 54% of Latinos.
Traditionally, manufacturers must prove a vaccine’s safety and efficacy by completing studies of at least 30,000 people, including people in high-risk categories. And they must track participants for at least two months — when most problems appear — after the last injection.
Even a vaccine that is little-studied and works just 50% of the time — the current FDA standard — could save many lives.
What is “emergency use authorization”? It says, in essence: “We’re in crisis.
And we’ve collected enough data to think that we’ve got something that could help.” Based on the FDA’s interim analysis, it allows a vaccine’s use with only partial data and before completion of the gold standard: a large and lengthy randomized trial.
Rather than offering the vaccine to everyone, experts say the safest, although most conservative, step is to issue a “narrow” emergency use authorization. This would mean, for example, that only health care workers would get access.
“I think the solution is give emergency use, based on partial data, if it looks good — but keep it narrow,” said Arthur Caplan, bioeth
icist at New York University Langone.
At the Thursday meeting, the FDA broached the prospect of even more-limited access, providing a vaccine on a case-by-case personal basis.
Advisers warned that a hastily granted emergency authorization could create major problems.
For instance, there might not be adequate data to show efficacy in subgroups of vulnerable people.
“Since severe disease and death are occurring primarily among minorities with this virus, if we put a vaccine out there that does not address that issue, it’s going to perpetuate the perception that segment
of our population does not matter much,” said committee member James E.K. Hildreth Sr., president of Meharry Medical College.
It also could interrupt a vaccine trial’s longer and more thorough ongoing research.
Why? Because if there’s evidence that a vaccine is working, everyone getting the inactive placebo might want the real thing.
While the FDA asserted that companies would be expected to continue the trial, some bioethicists said it is not fair to insist that research volunteers can’t switch over. They may just drop out.
This could end the study, because no one would be left in the placebo “arm” of the trial. And valuable information about the vaccine — how do the two groups compare over time? — would be lost.
An emergency use authorization could also sabotage other vaccine studies.
This is a problem, because the first authorized vaccine may not be the best. And different vaccines may work differently in diverse populations. For instance, some may offer better protection to the elderly, while others might be better in pregnant women.
But why would anyone volunteer for a research study if there’s a product already on the market?
Even if a potential vaccine holds the promise of working better — if it’s effective 60% of the time, as opposed to 50%, for instance — that may not be enough to convince people to volunteer.
Incremental improvements in safety and efficacy take time to reveal themselves. And that’s expensive.
And because an emergency authorization looks at short-term data, it doesn’t capture more subtle downstream issues — such as whether a vaccine protects against disease but not transmission, dangerously fueling the spread of the virus.
Thursday’s FDA meeting was a milestone in the nation’s effort to conquer COVID-19. But the debate is just beginning. The committee will hold more meetings as vaccine makers submit their applications — which could begin arriving as soon as mid-November.