The Red Flags That Alarm Experts as COVID-19 Vaccine Trials Reach Final Stage

• As President Donald Trump pushes for a COVID-19 vaccine by Election Day, health experts are keeping an eye on the integrity of the vaccine approval process.
• The appearance that the Trump administration is rushing the COVID-19 vaccine process for a pre-election win is affecting an already vaccine-hesitant public.
• Multiple phase 3 vaccine trials are being conducted worldwide.

With President Donald Trump’s repeated predictions that a COVID-19 vaccine will be available by Election Day on Nov. 3, along with signs of administration interference in federal science agencies, some health experts are on alert for red flags signaling that a vaccine was rushed and potentially unsafe.

To get a sense of what these red flags might look like, Healthline talked to experts about what they would want to see before a COVID-19 vaccine is approved.

Put science before politics

The tension between science and politics is nothing new — think: the U.S. inaction on climate change and the undoing of science-based clean air and water rules — but the COVID-19 pandemic has enlarged the chasm between the two.

This battle has been on full display in the country’s science agencies, as political appointees have attempted to shape the COVID-19 narrative in ways not supported by science.

In March, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for the decades-old malaria drug hydroxychloroquine, touted by Trump as a COVID-19 treatment.

The agency later withdrew the EUA when studies showed that the drug didn’t work, and that some people had severe side effects.

Then in August, an EUA issued by the FDA for convalescent plasma — another treatment pushed by Trump — raised additional concerns.

Even with a lack of high-quality clinical data, FDA Commissioner Dr. Stephen M. Hahn exaggerated the benefits of this treatment at a press briefing with Trump.

More recently, the Centers for Disease Control and Prevention (CDC) posted guidance last week saying that the new coronavirus could spread by airborne transmission, but within days removed that information from its website.

This has raised concerns that political pressure, not science, is driving these public health messages.

The appearance that the Trump administration is rushing the COVID-19 vaccine process for a pre-election win is affecting an already vaccine-hesitant public.

The percentage of Americans who said they would get the vaccine if it were available today has dropped to 51 percent in September from 72 percent in May, according to a recent Pew Research Center poll. Republicans were more averse to vaccination than Democrats in both polls.

With so much at stake here, there are signs that the FDA is recommitting itself to a strong regulatory review of potential COVID-19 vaccines.

Kelly Goode, PharmD, a professor in the department of pharmacotherapy and outcomes science at Virginia Commonwealth University School of Pharmacy, says the FDA is expected to announce “more stringent” standards for an EUA of a COVID-19 vaccine.

This shift is needed, she says, because a vaccine will be given to healthy people, compared to other emergency treatments, which are administered to people with serious illness.

The Washington Post reports that with the tough new EUA standards for a COVID-19 vaccine, it will be “exceedingly difficult” for a vaccine to be approved before Election Day.

On Wednesday, Trump claimed he may override any new COVID-19 vaccine regulations by the FDA, according to CNN.

Run the right clinical trials

Dr. Susan Koletar, an infectious disease expert and chair of the department of infectious diseases at The Ohio State University Wexner Medical Center, thinks it would be “unwise” to make a vaccine available next month.

“I hope there will a vaccine sooner than later,” she said, “but we shouldn’t sacrifice safety to push that forward.”

Still, she’s confident that the COVID-19 vaccine trials are designed to assess both safety and effectiveness of the candidate vaccines.

She points to the recent pause of AstraZeneca’s vaccine trial as a sign that the scientific process is working.

The company’s worldwide phase 3 clinical trial was put on hold earlier this month after a woman given the vaccine at a U.K. site developed a neurological problem.

This pause was initiated to allow investigators to determine whether the problem was caused by the vaccine. The trial has resumed in the United Kingdom but is still on hold in the United States.

Koletar says this kind of pause in a clinical trial isn’t unusual.

“As an investigator, it makes me feel good that there are systems in place to really ensure the safety,” she added.

The large size of the phase 3 trials is also an advantage.

Moderna and AstraZeneca are each aiming to enroll around 30,000 people; Pfizer will have around 44,000. Johnson & Johnson, which started its trial this week, will enroll up to 60,000 people.

In order to know whether the vaccine works, people given the vaccine — and the other half who receive the inactive placebo — have to be exposed to the virus. Enrolling many people upfront is one way to speed up the phase 3 trials, says Koletar.

Another important consideration for these trials, says Goode, is the study’s endpoint — or what question they’re trying to answer.

Is it that the vaccine reduces the risk of moderate or severe COVID-19? Or that the vaccine reduces the transmission of the coronavirus?

Goode says most studies are looking at whether the vaccine reduces or prevents COVID-19.

However, Dr. Eric Topol, a professor of molecular medicine at Scripps Research, and Peter Doshi, PhD, an associate professor at the University of Maryland School of Pharmacy, write in The New York Times that with the way the trials’ protocols are written, “a vaccine could meet the companies’ benchmark for success if it lowered the risk of mild COVID-19.”

So, we may not find out whether a vaccine protects against moderate or severe disease — unless the studies are allowed to run long enough to answer this question.

While phase 3 trials are essential, Koletar says they’re not the final word.

Additional studies are needed to answer other important questions, such as how long immunity provided by a vaccine lasts, whether people will need yearly booster shots, or if there are rare side effects of the vaccine.

“We have a lot of things to learn,” she said. “But I am impressed with the science, and I think we need to keep following the science to move forward.”

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