FDA head walks back claim of dramatic benefit from COVID therapy

The head of the US Food and Drug Administration (FDA) walked back his claim that an experimental therapy had provided a dramatic benefit to COVID-19 patients, a rare reversal for an agency that has prided itself on rock-solid science and public trust.

On Sunday night at a press conference with President Donald Trump, FDA Commissioner Stephen Hahn said that blood plasma from COVID-19 survivors given to new patients could save huge numbers of lives.

“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,” Mr. Hahn said. Hahn’s remarks followed similar comments by Mr. Trump, who said that the therapy is “proven to reduce mortality by 35%,” and by Health and Human Services (HHS) Secretary Alex Azar.

On Monday night, Mr. Hahn reversed himself.

“I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified,” Mr. Hahn said in a tweet.

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.

— Dr. Stephen M. Hahn (@SteveFDA)

Mr. Hahn had spent much of Monday taking heat from health experts, including two former FDA commissioners, for his remarks.

“That was not the way that I would have worded it,” said one of the doctors who led the blood plasma study, Arturo Casadevall, chair of the department of molecular microbiology and immunology at the Johns Hopkins School of Public Health. “I hope they will issue a clarification,” he said earlier Monday.

What the data do show is that a higher dose of blood plasma is better than a lower one. And while there are promising signals that it will lead to a real benefit when compared to a placebo, that’s not known yet.

“Until we have a randomized controlled trial, we don’t know definitively,” Mr. Casadevall said.

The administration’s misrepresentation of the data may raise fears about how Mr. Hahn and the rest of the administration will treat data on a vaccine for the virus. Mr. Trump has said he expects one to be ready in time for his potential re-election, and on Saturday accused unnamed members of the “deep state” at the FDA of slowing work to hurt him politically. The “deep state” is a term used by Mr. Trump to describe employees of government agencies that he believes are manipulating policy to work against his interests. There is no evidence this is happening at the FDA.

The 35% statistic also has several fatal flaws. Since everyone in the program received blood plasma, it’s not known what would have happened compared with patients who didn’t get the therapy. And scores of variables, like how sick the patients were and when they were treated—that could have skewed the results.

Robert Califf, the FDA commissioner under President Barack Obama, said that he thought Hahn had misspoken. “It would be good for Steve to publish a correction,” Mr. Califf said on earlier Monday.

Messrs. Azar and Hahn both have extensive experience with drugs and therapies. Mr. Azar is a former pharmaceutical executive, and Mr. Hahn has spent several decades treating patients and researching cancer. Before joining the FDA, he was the chief medical executive of the University of Texas MD Anderson Cancer Center, a leading oncology treatment and research hospital.

In a posted earlier Monday, Mr. Hahn said that the agency will “reevaluate our emergency use authorization (EUA) based upon new incoming data that we receive.”

WIDE USE

Blood plasma from recovered patients is being used around the world, with the hope that its infection-fighting antibodies can help combat the virus. It doesn’t appear to pose a major safety risk, and on Sunday the Trump administration announced an emergency FDA measure to make it more widely available. Several studies have shown promising signs of efficacy.

“Based on the data we have today, it’s very likely that plasma is reducing mortality,” Mr. Casadevall said. “The one thing we are missing is a randomized controlled trial,” the gold-standard test that will tell researchers and regulators if blood plasma is a breakthrough, an incremental help or something in between.

To understand the confusion over the 35% figure, it’s important to look at two concepts: relative risk and absolute risk.

Imagine a clinical trial to test an experimental drug, with 2,000 patients split into two groups. The first 1,000 patients don’t get the drug, and in that group 10 people die. The other group of 1,000 patients gets the drug, and five people in that group die.

Using relative risk, that’s a 50% improvement—a tremendous number. But using absolute risk, the imaginary drug only decreases the likelihood of death by 0.5%. That means 5 more of those 1,000 people treated with the drug would live, not the 500 implied if you mistakenly use the 50% relative risk number.

The claim of a 35% mortality benefit made by Messrs. Trump, Azar and Hahn uses the first measure—relative risk. But because clinical trials of plasma therapy haven’t been completed, how many lives it actually saves—the absolute risk improvement—still isn’t known.

Mr. Hahn, in his tweet Monday, said he had muddled the difference. “What I should have said better is that the data show a relative risk reduction not an absolute risk reduction,” he said.

The FDA analysis was pulled from a subset of data in the trial—typically a no-no for credible studies. And despite a day of criticism online from doctors and researchers, Mr. Hahn’s correction wasn’t enough for some.

“You need to correct the 35 lives saved per 100 sick with COVID-19 so people understand that was absolutely wrong, Steve,” Eric Topol, director of the Scripps Research Translational Institute in California, said on Twitter. “That there is no evidence to support that. That there is no evidence at this juncture to support *any* survival benefit.”

TWEETS

Doctors and patients rely on the FDA to put out authoritative information about the safety and efficacy of drugs, vaccines, medical devices, and other products, guiding their use not just in the US but around the world. The agency has historically carefully guarded its reputation and scientific independence,

Mr. Hahn’s comments about 35 out of 100 people being saved were still posted to the FDA’s official twitter account as of Monday afternoon.

Emily Miller, the FDA spokeswoman, repeated the error in a tweet after the press conference, saying “convalescent plasma has shown to be beneficial for 35% of patients.” While she in a follow-up message about an hour later, the FDA’s main twitter account still carries Mr. Hahn’s misstatement.

Alyssa Farah, a White House spokeswoman made a similarly misleading tweet, saying that the therapy cuts mortality by 30% to 50%. And Michael Caputo, Mr. Azar’s chief spokesman at HHS, echoed the claim: “If you’re one of the 35 people out of a hundred who survive severe COVID symptoms because of convalescent plasma, you’re damn right this is a BREAKTHROUGH.”

If you’re one of the 35 people out of a hundred who survive severe COVID symptoms because of convalescent plasma, you’re damn right this is a BREAKTHROUGH.

— Michael R. Caputo (@SpoxHHS)

Ms. Farah didn’t respond to emails requesting comment. Mr. Caputo deferred comment to the FDA, though his tweet with the incorrect information was still up as of 10 p.m. Monday in New York.

Mr. Hahn’s predecessor Scott Gottlieb, who served as FDA commissioner under Mr. Trump from 2017 to 2019, said he thought the FDA was right to allow convalescent blood plasma for emergency use. But he suggested the press conference hadn’t given the correct picture of what health regulators actually know from the data.

“When we overstate findings it erodes confidence in science and undermines public trust in regulatory decisions. The right message was this ‘may’ provide a benefit, it could be meaningful for some patients, but we need more evidence to prove it,” Mr. Gottlieb said in a tweet.

“The way the public part was handled will erode precious public confidence,” he said. “You earn public confidence in small drops and you lose it in buckets.” — Bloomberg