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Biocentury – Ex-FDA officials: EUA may be merited, but FDA put politics ahead of science

Biocentury – Ex-FDA officials: EUA may be merited, but FDA put politics ahead of science

FDA Commissioner Stephen Hahn’s decisions and comments about granting Emergency Use Authorization for convalescent plasma to treat COVID-19 have put politics ahead of science, former senior FDA officials told BioCentury.

“At this moment in time, the FDA can no longer call itself an independent and science-based regulatory agency,” Luciana Borio, former acting FDA chief scientist, told BioCentury.

Borio, who served in the Trump administration as the National Security Council’s director for medical and biodefense preparedness policy, added that although tens of thousands of COVID-19 patients have been treated with convalescent plasma, its proponents “have to do statistical acrobatics to show a benefit. All of the studies that underpin [the EUA] are biased.”

The EUA, and especially comments from the administration touting the efficacy of convalescent plasma, compromise ongoing and future clinical trials of potential COVID-19 treatments, including mAbs, Borio said.

“People are wary of participating in clinical studies, especially if they believe there is an effective treatment,” she said. “Who would want to risk getting a placebo if they think there’s something better available?”

“FDA can no longer call itself an independent and science-based regulatory agency.”
Luciana Borio

Other former FDA officials said that while the EUA may have been justified, President Donald Trump, Hahn, and HHS Secretary Alex Azar have damaged FDA’s credibility by politicizing the authorization decision and announcement.

The EUA came after pressure from the White House.

“The deep state, or whoever, over at the FDA is making it very difficult for drug companies to get people in order to test the vaccines and therapeutics. Obviously, they are hoping to delay the answer until after November 3rd. Must focus on speed, and saving lives! @SteveFDA,” Trump said in a tweet.

Hahn conceded that the criticism was “entirely justified;” however, he pushed back on the suggestion that politics influenced FDA’s decision. He said the agency is committed to being “data driven” in its work.

“The decision was made by FDA career scientists based on data submitted a few weeks ago,” the commissioner said in a tweet on Monday.

Patient groups defended FDA against White House attacks. “We all want these unprecedented efforts to combat COVID to be successful, but introducing conspiracy theories, politics, and doubt into a scientific process is not the route we need now,” Ellen Sigal, chair and founder of Friends of Cancer Research, told BioCentury. “We need to stand up and support the hard-working people who have dedicated their lives to public health and those who have scarified so much for the benefit of patients.”

Joshua Sharfstein, FDA principal deputy commissioner for two years during the Obama administration, told BioCentury that while convalescent plasma is “a promising therapy,” there are questions about whether the EUA is “a good idea.”

Sharfstein, who is vice dean for public health at the Johns Hopkins Bloomberg School of Public Health, said he was troubled by FDA’s failure to provide a scientific rationale for the EUA, and he was scathing in his criticism of Trump for attacking the agency’s integrity and of Hahn for failing to defend FDA.

Trump said at a Sunday press conference announcing the EUA that it is his “very strong opinion” that FDA officials and employees of other HHS agencies deliberately delayed the EUA “for political reasons.”

This assertion, Sharfstein said, was “disgraceful, and the fact that the FDA commissioner was standing next to Trump smiling when he said it was shameful.”

Like Sharfstein, Jesse Goodman, former director of FDA’s Center for Biologics Research and Evaluation and former FDA chief scientist, believes the data on convalescent plasma may meet the bar for granting an EUA.

But he added that “it is not clear that there is a compelling reason for issuing an EUA now” because access to convalescent plasma is widespread under the existing expanded access program.

Former FDA Commissioner Scott Gottlieb, who held the office under Trump from May 2017 to April 2019,  tweeted that available data for plasma meet the criteria for an issuing an EUA, adding that it is “probably incrementally helpful to Covid patients.” However, he added that “better evidence generation” was necessary.

Supporting both the need for impartiality and his trust in FDA staff, he wrote: “We need to keep FDA decisions with FDA. The FDA professional staff supported this. It’s their decision.”

The Infectious Diseases Society of America (IDSA) suggested the EUA decision was premature, and called for randomized controlled data to understand the therapy’s utility in COVID-19 treatment.

“IDSA supports the continued collection of data in randomized clinical trials to better understand the benefits of convalescent plasma treatment before authorizing its wider use in patients with COVID-19,” IDSA President Thomas File said in a statement.

Regardless of the merits of granting an EUA for convalescent plasma, the Trump administration’s politicization of the process has damaged FDA’s credibility, Goodman said.

“Continuing pressure from the White House and the president on FDA’s decision-making risks compromising its independence, not to mention further undermining already compromised public trust in its independence and therefore the perceived integrity of important decisions to come,” Goodman, a Georgetown University professor, told BioCentury.

Borio, Goodman and Sharfstein were critical of statements from the Trump administration about the efficacy of convalescent plasma. Speaking at the press conference, Trump said, it has been “proven to reduce mortality by 35%. That’s a tremendous number.”

Hahn said, “A 35% improvement in survival is a pretty substantial benefit.” He added: “If you are one of those 35 out of 100 people who these data suggest or show survive as a result of it, this is pretty significant for that person and their family.”

Azar said the survival benefit is something most drug developers can only dream of achieving.

These statements are inaccurate and misleading, Borio and Goodman said. It is impossible to draw firm conclusions from an uncontrolled study, they said.

“There are hints of potential efficacy from those data but the therapy remains unproven,” Goodman said. It is not clear, he added, that the analyses of the data were prospectively identified.

Eric Topol, founder and director of Scripps Research Translational Institute, said in a tweet, “There’s no evidence to support any survival benefit” for convalescent plasma. He called Trump, Hahn and Azar’s claim that the treatment led to a 35% survival “outrageous.”

In a tweet ahead of the authorization, he, too, pointed to the lack of randomized trials, and noted that convalescent plasma “contains many antibodies that have no neutralizing effect. If it has efficacy, it will be relatively modest, at best.”

In a television interview Sunday morning before the EUA was announced, Gottlieb cautioned against drawing conclusions from the Mayo study. Speaking on CBS’s Face the Nation, he said it “wasn’t a very rigorously done trial. It was an open-label study where everyone got treated, so it’s hard to draw conclusions.”

In contrast to comments Trump administration officials made a few hours later, Gottlieb said convalescent plasma is “probably weakly beneficial in the setting of this treatment.”

In addition to warning against relying on an uncontrolled study, Goodman said, “there are also some significant imbalances in the study in comparison groups, a typical problem for any uncontrolled study.”