“It is proven to reduce mortality by 35 percent. It’s a tremendous number,” Trump said at the press conference. “Based on this data, the FDA has made the determination the treatment is safe and very effective.” That last part isn’t actually true yet—without large-scale randomized controlled trials, which haven’t happened yet, no one actually knows that for sure. Yet the agency has issued what’s called an Emergency Use Authorization, not quite an approval of the treatment but still giving the all-clear to physicians who want to administer the frothy, yellow liquid.
Based on the president’s comments and those of FDA head Stephen Hahn and HHS director Alex Azar, the data that tipped plasma into getting this Emergency Use Authorization came from a nationwide program to give people wider access to convalescent plasma, led by researchers at the Mayo Clinic. That program was not a large, randomized, controlled clinical trial, which is typically the standard for determining whether a treatment is safe and effective. That “expanded access program” did publish some outcomes in a preprint two weeks ago. It still hasn’t been peer-reviewed, but the researchers did keep track of the levels of antibodies, disease-fighting molecules, in the plasma administered to 35,000 people. It turned out that those people who received plasma earlier, and with the highest levels of antibodies, did have an increased survival rate. But the 35 percent number wasn’t for everyone who got plasma, just a specific statistical slice of the tens of thousands who received plasma sooner and with higher antibody levels. And even though the people who set up the expanded access program wanted to run concurrent randomized, controlled trials, that’s not what this was.
The timing of the announcement makes the whole thing even weirder. The president, who during this week’s Republican National Convention will presumably accept his party’s nomination to run for a second term, is under increasing pressure to show some progress in the fight against Covid-19—a disease from which nearly 175,000 Americans have died, with little sign of abatement. The only randomized trials that have published data on plasma so far have been small and, while promising, inconclusive.
Technically, that’s fine for an EUA. The criteria for issuing one really just demand reasonable safety and the possibility of usefulness. The agency still maintains that it’ll take actual randomized trials to make convalescent plasma into standard care. And it’s not clear that the authorization does anything that the expanded-access program wasn’t already doing, making sure anyone who wanted plasma could get it.
“It’s sufficient for an Emergency Use Authorization in the sense that most EUAs make no claim of benefit. They simply authorize utilization during the emergency, and when the emergency is over they are automatically canceled,” says Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center. “That said, this is one of the more frustrating examples, where we have had every opportunity to do proper randomized trials on convalescent plasma. The sole excuse offered back in February and March was, ‘We don’t have time,’ and it’s now nearly September.”
The Trump administration has deployed Emergency Use Authorizations before during the Covid-19 pandemic, and each time the EUA has been fraught in some way. The FDA issued one for the antimalarial and antiinflammatory drug hydroxychloroquine, even though most scientists were skeptical, to varying degrees, about its usefulness. (The agency revoked that one in June.) The agency issued another for the antiviral remdesivir, which physicians did want—but the agency initially seemed to do so based on data from a press release.
And here we are again with convalescent plasma. The risks this time: The same kind of politicization that hamstrung research on hydroxychloroquine could now slow down the hunt for plasma results, if people associate supporting the treatment with supporting the president (or not and not). People might be less likely to enroll in a trial, where they might be randomized to get a placebo rather than treatment, when plasma is now readily available. “It’s not like people aren’t excited about it. I love the idea of plasma. But now that it’s easy to give, and you can just write a prescription for it and you give it like a blood transfusion, with possibly no data or minimal data collected, it cuts the opportunity for doing great science,” says Peter Chin-Hong, an infectious disease physician at UC San Francisco.
Political influence may well have been a factor. The president has, without evidence, accused people who oppose him within the FDA of slowing down new treatments for Covid-19. The EUA comes just days after The New York Times reported that disease luminaries like Anthony Fauci of the National Institute of Allergy and Infectious Diseases and National Institutes of Health director Francis Collins were advising the FDA not to issue the authorization without more data. Trump, Azar, and Hahn ignored shouted questions about this at the end of the press conference. This concern will only get worse, especially if the same haste seems to surround the approval of an eventual vaccine. (The title on the FDA press release doesn’t help allay these concerns: “FDA Issues Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment, Another Achievement in Administration’s Fight Against Pandemic.”)
A little bootlickery? Maybe, but that’s just public relations and might not have anything to do with actual science. Doesn’t necessarily mean anything is off-kilter. “Some of the point people at the FDA I know personally, and the ones I don’t, I know professionally. They have the highest level of integrity,” says Shmuel Shoham, an infectious disease physician at Johns Hopkins University who’s running a major convalescent plasma trial, funded primarily by the Department of Defense. “A lot of times decisions are made based on information that is not a slam dunk, and you make the best decision you can with the information you have … But we have a deficit of the benefit of the doubt right now.”
So while it’s possible that convalescent plasma shows enough promise to warrant the issuance of an Emergency Use Authorization, it comes wrapped in caveats and suspicion, and risks implying outsize political influence at the FDA regardless of what actual trial data eventually shows. “All of this leads to mixed messaging and uncertainty among the population. It’s just another example of the weirdness that’s happening,” Chin-Hong says. Worse, nobody really knows if it’s going to help people with Covid-19, and this quick-fire bureaucratic designation doesn’t bring that knowledge any closer.