Lawmakers, experts raise questions after convalescent plasma EUA

Regulatory NewsRegulatory News | 25 August 2020 |  By 

After US Food and Drug Administration (FDA) Commissioner Stephen Hahn announced the issuance of an emergency use authorization (EUA) for convalescent plasma to treat coronavirus disease (COVID-19) alongside President Donald Trump on Sunday, experts and democratic lawmakers are raising concerns about how the announcement was presented and the perception of political pressure on the agency.
Convalescent plasma appears to meet the statutory standards for an EUA, which only require that a product “may be effective” and that its potential benefits outweigh its potential risks. However, the announcement prompted questions since it was timed just before the start of the Republican National Convention and a report last week from the New York Times that said the EUA was on hold after top officials at the National Institutes of Health voiced concerns about the strength of evidence in support of the therapy.
“The timing of the announcement, right on the heels of the President’s tweet criticizing the FDA as being part of the ‘deep state’ to delay approving therapies for the treatment of COVID19, raises significant concerns that the administration is applying political pressure on the agency,” Joseph Ross, professor of medicine at Yale University, told Focus. “Such political interjection diminishes public confidence in the agency, that its policies and decisions are guided by science and data and are being made in the best interests of patients and the public.”
Several democratic lawmakers raised similar concerns in a letter to Hahn on Monday. “We are increasingly concerned by the political pressure that is being exerted by this Administration on FDA,” Reps. Frank Pallone (D-NY), Anna Eshoo (D-CA) and Diana DeGette (D-CO) wrote. “Any political involvement in a future vaccine or treatment threatens to undermine the credibility of the agency, and public confidence in vaccines and treatments approved for use by FDA.”
In the letter, the representatives call on Hahn to address how the agency will safeguard itself from political pressure or the appearance of political interference and to lay out the steps the agency will take to “ensure that the evidence of safety and efficacy of a future vaccine will guide any and all decisions to issue an EUA prior to full licensure and approval of a COVID-19 vaccine.”
Much of the controversy centered around how Hahn presented data from the expanded access protocol for convalescent plasma run by the Mayo Clinic and used in part to support the issuance of the EUA.
“In the optimal patients … treated with convalescent plasma at the highest titers, there was a 35% improvement in survival, which is a significant clinical benefit,” Hahn said during the press conference, noting that, “This clearly meets the criteria that we’ve established for emergency use authorization.”
Hahn went on to say that, “A 35% improvement in survival is a pretty substantial clinical benefit. What that means is—and if the data continue to pan out—100 people who are sick with COVID-19, 35 would have been saved because of the administration of plasma.”
Experts were quick to point out that the 35% figure Hahn cited referred to the reduction in relative, not absolute, risk between patients who received high- and low-titer units of plasma.
On Twitter, former FDA Commissioner Scott Gottlieb said that convalescent plasma is “probably incrementally helpful” to patients with COVID-19, but nonetheless meets the statutory standard for an EUA.
“The data FDA had supports an authorization for emergency use, where the standard is ‘may be effective’ but we need better studies to confirm preliminary findings,” Gottlieb said.
Gottlieb’s predecessor, Robert Califf, noted Hahn’s misstatement, tweeting, “It would be good for Steve [Hahn] to publish a correction. I’m sure he meant to correctly state the translation from relative effect to absolute effect.”
On Monday evening, Hahn took to Twitter himself to address the issue: “I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.”
Hahn also disputed the notion that politics played into the agency’s decision to issue the EUA. “Media coverage of FDA’s decision to issue emergency authorization for convalescent plasma has questioned whether this was a politically motivated decision. The decision was made by FDA career scientists based on data submitted a few weeks ago,” he wrote.
Jonathan Darrow, assistant professor at Harvard Medical School, told Focus that it is too early to tell how Hahn’s statements will impact public perception of the agency. “Whether comments of FDA officials undermine public trust probably turns most on how close these estimates end up approaching the truth, which cannot be predicted in advance,” he said.
Darrow also pointed out that drugmakers often report relative rather than absolute risk data about their products. “Rather than criticizing Hahn, it would be more productive to ensure that medical journals, TV advertisements, and FDA labeling (among others) always report the absolute risk reduction clearly. Hahn is hardly the first person to present data this way.”
Stanford Law Professor Hank Greely told Focus that while research would need to be done to measure any change in public perception of FDA, “Especially in a context where vaccines seem likely to be important in controlling the pandemic and anti-vaccine sentiment is significant, injecting more, and real, reasons to doubt the FDA seems dangerous.”


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