In 1903, the agency that would later become part of the US Food and Drug Administration approved its first vaccine. Now the FDA has more than 80 licensed vaccines, and for each there has been an established scientific protocol to make sure it’s safe and effective.
But this is 2020, the year when nothing is normal.
Despite reassurances from federal officials, there are fears that the typical pathway for review and approval of the Covid-19 vaccine will be eschewed, or at least bent, because of political pressure.
Two former FDA commissioners tell CNN that while they think it’s very unlikely that President Trump could pressure scientists into authorizing or approving a Covid-19 vaccine, it’s possible.
Trump has said he thinks a vaccine could be available by Election Day on November 3, repeating the possibility again at a rally Thursday.
“It will be delivered before the end of the year, in my opinion, before the end of the year, but it really might even be delivered before the end of October,” Trump said. “How do you like that? Wouldn’t that be nice? And you know why? Not because of the election. It’d be nice because we want to save people.”
Such early expectations from the President make some experts nervous.
“What I’m concerned about is there could be a gray zone where a vaccine looks partially protective and it goes on the market without a full formal review process,” said Dr. Peter Hotez, a vaccinologist at Baylor College of Medicine.
How vaccines are evaluated
Currently, three large, US-funded clinical trials for coronavirus vaccines are underway by pharmaceutical companies Pfizer, AstraZeneca and Moderna.
Each trial involves 30,000 adults who have volunteered to participate. Half will get two doses of the vaccine, and half will get two doses of a placebo, which is a shot of saline that does nothing. The two doses are spaced several weeks apart.
Both the participants and the researchers are “blinded,” which means neither knows who got the vaccine and who got the placebo.
Then the wait begins.
During the trial, volunteers go about their daily lives. Researchers check in with them regularly, and record who gets sick with Covid-19.
The researchers have to feed their data to a group called the Data and Safety Monitoring Board, an independent group of experts set up by the National Institutes of Health.
Members of this board are the only people allowed to take a look at which volunteers got the vaccine and which received the placebo, and the members only do so under specific circumstances.
When a certain number of study participants become ill with Covid-19, the DSMB takes a look at how many of those sick volunteers received the vaccine and how many received the placebo.
For example, for Moderna, that first look – called an interim analysis – occurs when 53 study subjects become sick with coronavirus, according to Ray Jordan, a spokesman for the company.
Members of the DSMB check to see if significantly fewer people who received the vaccine became ill with Covid-19.
If that’s the case, the DSMB might recommend that the trial stop because the vaccine has been shown to work. If that’s not the case, then the trial likely would continue.
For Moderna, there’s a second interim analysis after 106 volunteers get sick with Covid-19, and then another analysis when 153 volunteers fall ill.
If the DSMB finds that a vaccine seems to protect against coronavirus, the data is then reviewed by an FDA advisory committee.
That committee – formally known as the Vaccines and Related Biological Products Advisory Committee – has 17 members, most of whom are infectious disease specialists at universities and research centers.
The advisory committee’s recommendation goes to the FDA’s Center for Biologics Evaluation and Research, which typically agrees with the committee’s findings. The head of that center, Dr. Peter Marks, then sends his recommendation to Dr. Stephen Hahn, the FDA commissioner.
That’s where the worries begin.
Concerns about political pressure
The experts are concerned that Hahn, under pressure from the Trump administration – or feeling the pressure of a deadly pandemic – could authorize or approve a vaccine, regardless of recommendations from any of the experts who examined the data.
Hahn has repeated several times that the FDA’s decision will be based on data and science.
“I can promise you that when the data are available, FDA will review them, using its established rigorous and deliberative scientific process,” he told the Journal of the American Medical Association last month. “We all understand that only by engaging in an open review process and relying on good science and sound data, can the public, and you as providers, have confidence in the integrity of our decisions.”
On Tuesday, when he was asked by CBS News if he would consider resigning if he was pressured to make a Covid-19 vaccine available prematurely, he answered, “I think all options are on the table. With respect, I hope we won’t be in that position.”
Even if Hahn makes the right decision based on science, he could be overruled. It’s rare – but it has happened before.
In 2011, Kathleen Sebelius, US Health and Human Services secretary during the Obama administration, overruled an FDA recommendation about making a contraceptive pill available over the counter to girls younger than 17.
That FDA commissioner, Dr. Margaret Hamburg, told CNN Friday that this kind of political bigfooting can happen at any time.
“People think the FDA is an independent regulatory agency, but it’s not at all – it’s part of the Department of Health and Human Services, which is a Cabinet department – the secretary reports to the White House,” said Hamburg.
And the White House has made it clear that the President wants a vaccine by Election Day.
Another former FDA commissioner, Dr. Robert Califf, said he was concerned even before Covid-19 that Trump would pressure the FDA to make decisions his way.
“One of the things that’s had me on pins and needles the last four years is literally Trump could do this with any drug or device or vaccine anytime he wants to,” said Califf, who was commissioner from January 2016 through January 2018.
He said the pressure might even be greater during the pandemic, since the country wants to get back to normal as soon as possible.
“If you want to talk about a chilling experience, when you become FDA commissioner you have top secret briefings about what actions get triggered when there’s nuclear attacks, nuclear accidents, hurricanes, tornadoes, earthquakes and pandemics,” he said. “And think about it, if we had a nuclear attack against us, we wouldn’t want the FDA saying ‘we want five years of follow up on a potential treatment for radiation.’”
Califf said despite this, he thinks it would be “an extraordinarily unlikely scenario” for Trump to go against the advice of his scientific advisers.
Even if that were to happen, Califf thinks doctors would step in and advise their patients not to get a vaccine that hadn’t been proven safe and effective.
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“The medical community is not going to accept it, and most people won’t get a vaccine if their doctor tells them not,” he said.
Hamburg, who was FDA commissioner from 2009 until 2015, said she agrees that it’s unlikely that a coronavirus vaccine will get onto the market before trial results are clear, but adds that the Trump administration is unpredictable.
“I had all sorts of confidence that checks and balances would prevent all sorts of things in this administration, but it didn’t happen, so maybe I was overly optimistic,” she said. “I think you never know with this White House.”
CNN’s John Bonifield and Wes Bruer contributed to this report.