This process will determine how quickly we get a coronavirus vaccine

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Emergency use authorization is what its name suggests: a medical product that gets special authorization by the US Food and Drug Administration to be used during an emergency. Sometimes it’s a product that has already been FDA-approved, but for another condition, and sometimes it’s a new product that hasn’t yet received the agency’s green light.

There is a lot of ongoing concern and debate about whether any vaccine candidate should be granted an EUA — or outright approval — without first completing Phase 3 clinical trials.

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But that’s only if “the known and potential benefits of the product, when used to diagnose, prevent, or treat the identified disease or condition, outweigh the known and potential risks of the product.”

So, in essence, what an EUA does is speed up the process of getting potentially helpful  medical products authorized for a specific use to the public during a health emergency, without the rigorous testing and subsequent scrutiny that’s usually required to get FDA approval — which traditionally takes years.

When the health emergency is over, “then any EUA(s) issued based on that declaration will no longer remain in effect,” according to the FDA. But the manufacturer can still submit documentation to the agency for regular approval.

The EUA hasn’t been around that long. The process was included within the Project  Bioshield Act passed by Congress in 2004, which enabled the federal government to prepare and stockpile new “medical countermeasures” during a declared public health emergency.

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And despite issuing many EUAs over the years, only one vaccine has ever received one – but it was in an unusual and controversial circumstance. In 1997, the Department of Defense began a mandatory anthrax vaccination program. Shortly thereafter, soldiers claimed the vaccine made them sick, so they sued and a judge put a hold on the program in 2003. The Department of Defense asked for an EUA that then overrode the court ruling in 2005, so it could continue vaccinating military personnel — this time on a voluntary basis.

EUAs during this pandemic

During the Covid-19 pandemic, the FDA has granted EUAs many times to a wide range of medical products, such as ventilators; personal protective equipment, including masks; molecular and antigen tests to diagnose Covid-19, and serologic tests to look for antibodies; and even treatments, such as remdesivir  and convalescent plasma.

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An EUA can be revoked,as in the case of hydroxychloroquine and chloroquine. These drugs had already been approved to treat and prevent malaria, and showed promise against the novel coronavirus in laboratory studies. Small early trials in Covid-19 patients added to the optimism, and the medication was touted by President Trump. But larger studies found the medications to be ineffective in treating patients with Covid-19. Additionally, one of the side effects could also potentially be dangerous in people who had pre-existing heart conditions. After about two and a half months with EUA, the emergency authorization was revoked.

Many experts see granting an EUA to a vaccine against Covid-19 as problematic. For one, vaccines are given to healthy people by choice, unlike medications that are given to gravely ill patients who might die without them. So drugmakers have a higher bar, so to speak, to make sure there are no unexpected side effects that make healthy people sick — and the only way to find out is in large-scale trials, like those going on right now.

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The FDA has said it would hold a vaccine to a higher standard. Dr. Peter Marks, who heads FDA’s Center for Biologics Evaluation and Research, said Thursday that requirements will be stricter than for an emergency use authorization for an experimental drug.

“For us, for a vaccine for which there is adequate manufacturing information, if we going to do an emergency use authorization, it is going to really be like an emergency use authorization plus,” Marks told a seminar hosted by Duke University’s Margolis Center for Health Policy.

On Friday Marks and Hahn said in a joint blog post they’d be issuing more guidance “shortly” about how much higher the bar might be.

They noted it is up to the manufacturer to ask the FDA either for an EUA or full approval, known as a Biologics License Application. With so much at stake, we understand the importance of being as transparent as possible about the work we do, including how we will make decisions regarding COVID-19 vaccines,” Marks and Hahn wrote.

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The FDA has already said it would want to see an efficacy of at least 50% — meaning any vaccine, to be considered, would need to reduce the risk of infection or of serious illness by at least 50% over a placebo.

In a string of tweets by Dr. Peter Hotez, a professor and the dean of Tropical Medicine at Baylor College of Medicine, earlier this month, he noted that “EUAs involve substandard or lesser reviews. How can you justify a substandard or lesser review for something that would be injected in tens of millions, maybe hundreds of millions of Americans?”

Additionally, Hotez pointed out that the mRNA technology being used in two of the vaccines that are the furthest along in Phase 3 trials — the Moderna vaccine and the Pfizer/BioNTech vaccine — is “a new technology that has never before been licensed. We have no history or experience on such vaccines. Even more reason for a full/comprehensive review.”

Hotez also brings up the point that in this highly politicized climate, there is a lack of confidence and trust in the government and federal agencies. “We’ve seen how in 2020 the White House has abused the EUA mechanism – remember the EUA for hydroxychloroquine that was revoked? Neither does the White House or Dept. HHS,” he tweeted.

Political subtext

There is also the worry that the President is looking to make a vaccine available for political reasons during the run-up to the November election.

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President Trump has said several times he thinks a vaccine could be available by Election Day. Without a doubt, the pace of medical innovation has moved faster than ever before, and human vaccine trials began just 67 days after the virus was first identified. The US Centers for Disease Control and Prevention recently told public health officials to prepare to distribute a potential vaccine as early as end of October. And FDA Commissioner Dr. Stephen Hahn said he’d consider an EUA before Phase 3 trials are complete.

Still, several government health officials have told CNN the idea that a vaccine could be available to the general public by November 3 is unlikely. “There is a big concern about the sort of political expediency and when this [October] date was being picked … and just picking this date, before the election, sort of stokes those fears that the government isn’t being duly diligent to make sure that any vaccine really is not just efficacious, but has few side effects,” said Dr. Ali Khan, dean of the College of Public Health at the University of Nebraska Medical Center, and former director of the Office of Public Health Preparedness at the CDC.

“So, we’re all optimistic that there are currently three vaccines in Phase 3 trials — that maybe one of these vaccines is so excellent that you don’t need to vaccinate 30,000 people to find that it’s going to work. However, the concern is that if you don’t do a full set of these so-called Phase 3 trials, that you will miss rare side effects,” he said on CNN earlier this month.

When a vaccine — or other medical product — is given to enough people, rare side effects can turn up. In 1976, the government  launched a  hastily produced  vaccine about seven months after the Ford administration was led to believe a pandemic caused by a new strain of flu was imminent.

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The pandemic never materialized, but 40 million people got vaccinated under a compulsory program. That vaccine was later linked to a neurological disorder called Guillain-Barré syndrome, which can develop after an infection or, rarely, after vaccination with a live vaccine. The link was never proved, but the program was stopped.

Also, in order to demonstrate efficacy of the vaccine, dozens of people in the placebo group would need to become infected, while very few — if any — infections would be seen in the vaccinated group of trial participants. It may take weeks, if not months, to see that difference between the two populations.

Lack of trust

The lack of public trust and vaccine hesitancy are real. A CNN poll in August showed 40% of Americans do not want to get a vaccine when it becomes available — even if it is cheap and easy to get. Such a low uptake of the vaccine could hurt the country’s ability to get the virus under control and return to normalcy.

If history is any indication, skepticism — if not outright mistrust — about an unapproved vaccine is nothing new. In a study published in 2009, months after the US declared a public health emergency due to the H1N1 influenza and the World Health Organization declared it a pandemic, researchers explored the public’s willingness to use a drug or a vaccine with an EUA (not full FDA approval) by surveying a representative sample of more than 1,500 US adults. 

They found more than 77% of respondents would be moderately, very or extremely worried if offered an unapproved vaccine; 63% said they would not take it.

But there were also some other key factors that would convince respondents that a vaccine authorized under an EUA was safe to use. If the vaccine were administered by a public health professional, 55% of respondents say they would take it. If it came with a fact sheet, just over 57% of those surveyed said they would get it. And if it were administered by their own health care provider, that number shot up to 68%. Transparency is key in gaining trust.

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Those in charge of the country’s health agencies — Alex Azar at the US Department of Health and Human Services, Dr. Francis Collins at the National Institutes of Health, Dr. Anthony Fauci at the National Institute of Allergy and Infectious Diseases, the FDA’s Dr. Stephen Hahn and the CDC’s Dr. Robert Redfield — have all tried to reassure Americans that politics will not play a role in when a vaccine becomes available.

Fauci has said he believes a vaccine will likely come closer to the end of the year, and that he wouldn’t be comfortable with making a vaccine widely available unless the scientific evidence backed it up. “I’m not a regulator. I mean, I just do the science. I’d report the science in an accurate way, and certainly if I saw interference, I would be very disturbed and call it out,” Fauci told CNN’s Jim Acosta on “The Situation Room.”

As for an emergency use authorization, “I would not be comfortable with a vaccine unless it was shown in a clinical trial clearly to be safe and effective,” Fauci said during an interview on NBC’s “Today.” 

Dr. Luciana Borio, the former acting chief scientist at the FDA, agrees that a vaccine must be shown to be safe and effective first and foremost.

But if a vaccine is shown to be safe and effective in adequate and well-controlled clinical trials, it should not be withheld until all the stringent licensure requirements for FDA approval are met, because some of the requirements cannot be generated quickly.

“Safe & effective vaccines can save lives and help contain the pandemic,” Borio tweeted. “The EUA is the most appropriate regulatory mechanism for distributing vaccines that have been shown to be safe & effective in phase 3 RCTs (randomized controlled trials) but have not yet met all of the FDA’s standards for licensure.” 

Moncef Slaoui, chief adviser to Operation Warp Speed, the federal government’s Covid-19 vaccine program, said that “it would be unethical” to not move quickly to put out a Covid-19 vaccine if it is proven to work.

“If we know a vaccine is 70% or 80% or 90% effective, it would be unethical to hold it back,” Slaoui said during a CNN interview on Friday.

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On Tuesday, nine biopharmaceutical companies, including those who are furthest along in their vaccine testing programs, signed an unusual pledge to uphold “high ethical standards,” suggesting they won’t seek premature government approval for Covid-19 vaccines.

They pledged to “Only submit for approval or emergency use authorization after demonstrating safety and efficacy through a Phase 3 clinical study that is designed and conducted to meet requirements of expert regulatory authorities such as FDA.”

In fact, later that same day, AstraZeneca, one of the signatories of the pledge, said it had paused its trials globally because of an unexplained illness in one volunteer in the UK. The drugmaker called the halt “a routine action.”

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“In large trials, illnesses will happen by chance but must be independently reviewed to check this carefully. We are working to expedite the review of the single event to minimize any potential impact on the trial timeline,” AstraZeneca said in a statement sent to CNN.

According to the FDA’s guidance, any vaccine — whether under emergency authorization or approved — needs to either prevent disease or at least decrease severity by at least 50%.

Despite all the intrigue, it may be worthwhile to circle back to the original criteria for an EUA — in particular, the stipulation that it only be granted when ”there are no adequate, approved, and available alternatives.”

While most people understandably don’t want to hear it, there is a reasonable alternative, which has worked well  in many places around the world, and that is abiding by basic public health measures: wearing a mask, maintaining physical distance, practicing good hand hygiene and staying away from large, especially indoor crowds — especially indoors.

Following those rules will significantly reduce the likelihood of people getting sick, and slow the transmission of the virus. It will also buy us more time to make sure we get the evidence supporting the vaccine totally nailed down.

CNN’s Jen Christensen, Shelby Lin Erdman, and Nadia Kounang contributed to this report.

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