On Sunday, the Food and Drug Administration issued an “emergency use authorization” for blood plasma to treat COVID-19. The decision was well within the agency’s remit but nevertheless generated instant controversy. President Donald Trump had just attacked the “deep state” at the FDA for holding up COVID-19 treatments; the next day, the normally staid and careful agency was cheerleading plasma as “another achievement in administration’s fight against pandemic.” The FDA commissioner, Stephen Hahn, boasted that plasma could save 35 out of 100 treated COVID-19 patients if the data held up—a claim so grossly misleading, he had to recant it.
The limited evidence available suggests that infusing patients with the antibody-rich plasma of survivors is, at best, incrementally effective. One study found that patients who received plasma within three days of a COVID-19 diagnosis had marginally better outcomes than those who received it later. There is no randomized, controlled trial yet comparing patients who were given plasma with those who were not.
Even so, plasma does technically meet the low bar for “emergency use authorization,” or EUA, which is a much looser standard than formal FDA approval. The 2004 law that created the EUA process requires that “it is reasonable to believe that the product may be effective.” The flexibility is helpful in emergencies, but it can also backfire if exercised too often, too carelessly, or too politically. In the EUA mechanism, experts and former FDA officials fear, the Trump administration has found a soft spot vulnerable to political pressure, which could be especially intense as the agency begins reviewing data for COVID-19 vaccines.
“Almost any product that one would contemplate using for a human being would likely meet the criteria for EUA,” says Luciana Borio, a former acting chief scientist at the FDA who is now a vice president at In-Q-Tel. “Therefore it must be applied with tremendous responsibility.”
The FDA maintains that politics played no role in the blood-plasma EUA, but even the appearance of political meddling can erode trust in the agency. “Their credibility as a regulatory agency I fear has been damaged already,” says Sandra Quinn, a public-health researcher at the University of Maryland.
The FDA previously came under fire for issuing an EUA for hydroxychloroquine after Trump became fixated on the drug, which the agency later rescinded when the drug proved to be ineffective. With plasma, the agency has again issued an EUA following a loud and public campaign by the president based on little scientific evidence. The Trump administration is reportedly considering using the EUA process to fast-track a COVID-19 vaccine before the November election. “It just seems to be a pattern now,” says Jesse Goodman, a former chief scientist at the FDA now at Georgetown. “I’m very worried that this might happen with vaccines.” A controversial EUA for a vaccine could inflame fears that a vaccine is being rushed out.
Back in 2009, when the H1N1 flu was declared a pandemic, Quinn began studying whether the public would accept a vaccine authorized under emergency use. Willingness to get such a vaccine, she found, was low: 8.7 percent of the people she surveyed said they would get a “flu vaccine that was recently developed and not yet approved by the U.S. Food and Drug Administration,” 63.5 percent said no, and 27.8 were undecided. Only 4.2 percent of Black respondents said yes, which the study attributed to the legacy of mistrust from biomedical experimentation, such as the Tuskegee study, on Black Americans. Ultimately, no EUA was necessary for the H1N1 vaccine, which was approved through normal processes because of its similarity to the seasonal flu vaccine.
Only in one convoluted and somewhat exceptional case has a vaccine ever been authorized for emergency use. In 2004, a judge suspended a mandatory anthrax vaccination program for members of the military after ruling that the FDA did not follow the proper procedure for approval; the FDA ended up issuing an EUA before reaffirming the vaccine’s safety and efficacy in a formal review. (In 2001, before the EUA mechanism was written into law, the anthrax vaccine was also offered to postal workers under an “investigational new drug” protocol. Participation was extremely low, Quinn says, partly because of mistrust between management and workers who felt they were being used as “lab monkeys” or “guinea pigs.”)
In some ways, vaccines are especially ill-suited for the EUA process, because they have to clear a higher bar than drugs do. Drugs are given to sick people; vaccines are given to healthy people, so the acceptable risks are much smaller. “I don't think one would want to use the vaccine based on the kind of minimal, uncontrolled, or preliminary evidence we sometimes see for therapies,” Goodman told me. “Absolutely not.” The EUA process is flexible, so it’s up to the FDA to decide what level of evidence to require for a vaccine. Goodman said he can envision a scenario in which a vaccine should be authorized for emergency use—for instance, after large clinical trials have been completed but before the FDA has finished a formal review. But given how the FDA has handled hydroxychloroquine and now blood plasma, the agency could do everything right with a vaccine and the decision might still seem suspect.
Emergency use can also have the perverse effect of making it harder to study the effectiveness of a new vaccine or treatment. “When EUAs are issued, enrolling patients in clinical trials is likely to be more difficult,” says Patti Zettler, a former associate chief counsel at the FDA who now teaches law at Ohio State University. Patients may not want to join a clinical trial, in which they could get a placebo, if they can be sure to get the treatment under the EUA instead.
In 2009, for example, the FDA authorized the drug Peramivir for emergency use in serious cases of H1N1 flu; only years later did a randomized, controlled trial show that the drug was ineffective in hospitalized patients. “That experience actually really reshaped the way the agency worked when I was there,” Luciana Borio told me. The agency learned a lesson—better to do the trial during the pandemic. That way, she said, "we can actually learn quickly enough which drugs have merit and which ones don’t that we can actually alter the course of the pandemic.” Unfortunately, we are relearning the same lesson during the COVID-19 pandemic, when a lack of robust clinical trials has hampered efforts to find effective treatments.
Given the stakes of a COVID-19 vaccine, Zettler told me she hopes that manufacturers, which can request emergency use authorizations from the FDA, will not want to hastily roll out a vaccine either. “I hope, in this instance,” she said, “the FDA is not the only backstop here.”