Why Scientists Are Wary of the FDA’s Emergency Use Authorization of Plasma for Covid-19

Why Scientists Are Wary of the FDA’s Emergency Use Authorization of Plasma for Covid-19

On Sunday evening, President Donald Trump announced news that his administration had earlier advertised as a “breakthrough” development in the ongoing pandemic: The Food and Drug Administration would issue an emergency use authorization for convalescent plasma donated from covid-19 survivors as a treatment for hospitalized covid-19 patients. But though scientists and doctors are genuinely hopeful that convalescent plasma may help patients, some experts are perturbed by how and why the administration made this move.

Convalescent plasma has a long history in medicine. People who survive an infectious disease such as covid-19 tend to produce antibodies against the specific germ that caused the disease; these antibodies are readily found in the yellow, liquid part of blood called plasma. By taking a survivor’s plasma and giving it to someone else still battling their infection, the theory goes, you can give that person a form of passive immunity that should temporarily boost their defences against the disease (“convalescent” simply refers to someone who is recovering from a disease).

Doctors have used convalescent plasma since the late 19th century, and it’s been routinely deployed as a hopeful treatment during outbreaks of difficult-to-treat diseases, such as Ebola. Early on in the covid-19 pandemic, doctors were similarly optimistic that convalescent plasma could be a treatment for this viral disease as well.

On the surface, it’s understandable why the FDA has decided to issue an EUA for convalescent plasma. As former FDA chief Scott Gottlieb has noted, an EUA should be used to expand access to a potentially useful experimental treatment in an emergency situation. And in the case of convalescent plasma, there is some evidence already available suggesting that it can lessen the severity of covid-19 or shorten the length of symptoms, though Gottlieb called for further evidence to support its use.

But experts and doctors in the field are worried about the political process surrounding this particular emergency authorization.

“There is no clear indication that convalescent plasma is effective, and it is not clear what the decision by the FDA is based on,” Krutika Kuppalli, an infectious diseases physician and assistant professor at Stanford University, said in an email. “There is not a good [randomised controlled trial] to show that convalescent plasma is effective for covid-19, and we should be making decisions based in science.”

Last week, the New York Times reported that Francis Collins, head of the National Institutes of Health, and Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, were among the experts who vetoed the FDA’s initial decision to issue an EUA for convalescent plasma, citing the lack of strong evidence for its benefits, particularly from randomised controlled clinical trials. Reporting later emerged that Trump administration official Peter Navarro had recently pressured the FDA to speed up its research of covid-19 treatments, accusing agency officials of being part of the “deep state.” During the week, Trump himself criticised the agency for its hesitation in issuing an EUA for plasma.

The thing is, patients with covid-19 were already getting convalescent plasma through the Mayo Clinic’s expanded access program and other similar efforts. In these programs, patients were first screened for eligibility through an established protocol, and their outcomes were tracked. But an EUA means that any doctor can prescribe the treatment at their discretion, without needing to document what happens afterward for an analysis later. (On Sunday, the Mayo Clinic announced that it would discontinue enrollment into the program in light of the FDA’s announcement.)

The EUA should make it easier for more patients to get ahold of plasma, but according to Peter Chin-Hong, an infectious disease specialist at the University of California San Francisco, the wide-scale rollout of convalescent plasma could also make it harder for doctors to recruit people into the large clinical trials that are needed to figure out if it actually works, since patients might not want to roll the dice and be enrolled into a control group. The extra demand will also probably put a strain on the limited supply of convalescent plasma.

“It just sends the message that, ‘OK, everyone, there’s enough evidence, let’s just go out and use it. Let’s open the floodgates so everybody can use it.’ So I think that’s really why people are concerned,” Chin-Hong said.

In announcing the decision, Trump stated that plasma was “proven to reduce mortality by 35 per cent.” FDA chief Stephen Hahn seemingly tried to walk back that comment, though he still implied that plasma could be shown to provide a 35% improvement in survival eventually. But there’s simply no research available right now that suggests this to be true.

It’s possible that Trump flubbed the interpretation of preliminary data from the Mayo Clinic, which found a difference in survival between hospitalized patients who got plasma three days into diagnosis and those who received plasma four or more days later (8.7% of those who got plasma within three days died in a week’s time, compared to 11.9% of those who got it later). But as experts have pointed out, this comparison was only between patients who received plasma, and it doesn’t provide solid evidence that plasma is an effective treatment.

Meanwhile, there is some evidence from small trials suggesting that plasma may not be all that useful for covid-19, and it hasn’t always worked out as an emergency remedy during past disease outbreaks. During the 2014-2015 Ebola outbreak in West Africa, for instance, plasma actually failed to provide any life-saving benefit. Even experts like Chin-Hong, who has prescribed convalescent plasma to covid-19 patients, wouldn’t consider it to be the sort of “breakthrough” that merits a grand reveal by Trump and the FDA.

“I mean, who makes a press release on a Sunday about convalescent plasma? It’s not like it’s a new miraculous story,” Chin-Hong said.

There are ongoing clinical trials of convalescent plasma in the U.S. and elsewhere. It’s still possible and even likely that plasma will turn out to help covid-19 patients, particularly if it’s given early and taken from donors with high levels of antibodies. But Chin-Hong and other scientists watching from the outside are alarmed about what this chain of events may mean for future developments in covid-19 research, particularly for a potential vaccine.

“I suspect the reasons behind the EUA for plasma treatment may have an ulterior motive: They are working to lower the bar for EUAs in general, in order to push what they really want — an EUA for a covid-19 vaccine,” said Peter Hotez, dean for the National School of Tropical Medicine at Baylor College of Medicine in Texas. Hotez and his team are currently working to develop a coronavirus vaccine.

Though Hotez is encouraged by the research on convalescent plasma and said he would gladly take it if he became sick with covid-19, he’s one of many experts who have become wary of the Trump administration’s messaging on a vaccine, particularly Trump’s stated desire to have one available before election day. Just this past weekend, it was reported that Trump has directed his administration to find a workaround of the clinical trial process that’s needed for regulatory approval of any vaccine or drug in the U.S., possibly by using vaccines being developed elsewhere in Europe.

[referenced id=”1241250″ url=”https://gizmodo.com.au/2020/08/the-biggest-unanswered-questions-about-a-covid-19-vaccine/” thumb=”https://gizmodo.com.au/wp-content/uploads/2020/08/17/ole4p1wjqypbnenul5sr-300×169.jpg” title=”The Biggest Unanswered Questions About a Covid-19 Vaccine” excerpt=”A vaccine for the coronavirus that causes covid-19 appears to be our best strategy to ending the current pandemic. Unfortunately, the fastest time frame in which scientists have managed to create any vaccine in history was four years, and there’s already plenty of scepticism surrounding the safety, availability, and effectiveness…”]

If the mess surrounding convalescent plasma is a preview of what may come this October for a potential vaccine, it’s a decision that’s likely to further erode public trust in science, experts have warned.

“It’s just so awful the way the White House confuses the real science with the fake science for their hidden agendas. But that’s the lesson: This is how anti-science movements work, they string real facts with falsehoods to create false narratives,” Hotez said.

Editor’s Note: Release dates within this article are based in the U.S., but will be updated with local Australian dates as soon as we know more.

The Cheapest NBN 50 Plans

It’s the most popular NBN speed in Australia for a reason. Here are the cheapest plans available.

At Gizmodo, we independently select and write about stuff we love and think you'll like too. We have affiliate and advertising partnerships, which means we may collect a share of sales or other compensation from the links on this page. BTW – prices are accurate and items in stock at the time of posting.