F.D.A. ‘Grossly Misrepresented’ Blood Plasma Data, Scientists Say


At a information convention on Sunday asserting the emergency approval of blood plasma for hospitalized Covid-19 sufferers, President Trump and two of his high well being officers cited the identical statistic: that the remedy had decreased deaths by 35 p.c.

Mr. Trump known as it a “tremendous” quantity. His well being and human providers secretary, Alex M. Azar II, a former pharmaceutical government, stated, “I don’t want you to gloss over this number.” And Dr. Stephen M. Hahn, the commissioner of the Food and Drug Administration, stated 35 out of 100 Covid-19 sufferers “would have been saved because of the administration of plasma.”

But scientists had been stunned by the way in which the administration framed this information, which appeared to have been calculated primarily based on a small subgroup of hospitalized Covid-19 sufferers in a Mayo Clinic research: those that had been beneath 80 years outdated, not on ventilators and obtained plasma recognized to include excessive ranges of virus-fighting antibodies inside three days of prognosis.

What’s extra, many consultants — together with a scientist who labored on the Mayo Clinic research — had been bewildered about the place the statistic got here from. The quantity was not talked about within the official authorization letter issued by the company, nor was it in a 17-page memo written by F.D.A. scientists. It was not in an evaluation performed by the Mayo Clinic that has been steadily cited by the administration.

“For the first time ever, I feel like official people in communications and people at the F.D.A. grossly misrepresented data about a therapy,” stated Dr. Walid Gellad, who leads the Center for Pharmaceutical Policy and Prescribing on the University of Pittsburgh.

It is very worrisome, he stated, given concerns over how Mr. Trump has appeared to politicize the process of approving treatments and vaccines for the coronavirus. Over the next couple of months, as data emerges from vaccine clinical trials, the safety of potentially millions of people will rely on the scientific judgment of the F.D.A. “That’s a problem if they’re starting to exaggerate data,” Dr. Gellad said. “That’s the big problem.”

When asked where the 35 percent figure came from, an agency spokeswoman initially directed a reporter to a graph of survival statistics buried in the Trump administration’s application for emergency authorization. The chart, analyzing the same tiny subset of Mayo Clinic study patients, did not include numerical figures, but it appeared to indicate a 30-day survival probability of about 63 percent in patients who received plasma with a low level of antibodies, compared with about 76 percent in those who received a high level of antibodies.

On Monday, Dr. Peter Marks, the director of F.D.A.’s center for biologics, evaluation and research, said that the agency reviewed published studies of plasma and conducted its own analysis of data from the Mayo Clinic’s program of hospitalized patients who received plasma. Although the size of the benefit varied, he said in a statement, “there appears to be roughly a 35 percent relative improvement in the survival rates of patients” who received the plasma with higher versus lower levels of antibodies.

He added: “Given the safety profile observed, the totality of evidence regarding potential efficacy more than adequately met the ‘may be effective’ standard for granting an Emergency Use Authorization.”

The publicly released data from the Mayo Clinic shows that, among the larger group of more than 35,000 patients, when plasma was given within three day of diagnosis, the death rate was about 22 percent, compared with 27 percent when it was given four or more days after diagnosis.

Dr. Eric Topol, a professor of molecular medicine at Scripps Research in La Jolla, Calif. and a longtime expert in clinical trials, said that convalescent plasma has not yet shown the benefit that Dr. Hahn described — and that he should issue a correction.

“He needs to come out with that, and until he does, he has no credibility as an F.D.A. commissioner,” Dr. Topol said.

On Monday night, after this article was published, Dr. Hahn tweeted about the scientific response to his remarks, saying the “criticism is entirely justified.” He clarified that his earlier statements suggested an absolute reduction in risk, instead of the relative risk of a certain group of patients compared with another.

In an interview on Monday, one of the Mayo Clinic study’s main authors, Dr. Arturo Casadevall of Johns Hopkins University in Baltimore, said he was also stumped. “Do I know where the 35 percent comes from?” he said. “No.”

Dr. Casadevall said that the F.D.A. had conducted its own analyses of the data, and that the paper he and his colleagues posted this month to a so-called preprint server — before it has been peer reviewed by a medical journal — contained only a portion of the total available data.

Dr. Casadevall said focusing on the 35 percent number distracted from the broader takeaway: that convalescent plasma shows promise, at a time when doctors have few other options. “I think that I would not focus so much on that — people can say things in many different ways, but I think that one has to look at the data,” he said. “I think the important thing is that all the indicators show a reduction in mortality.”

Emily R. Smith, an epidemiologist at The George Washington University Milken Institute School of Public Health in Washington, D.C., agreed that the issue was a distraction, but for a different reason.

“We’re trying to track down numbers and preprints and Twitter slides, and that’s a big distraction from the bigger issue of — do we think there’s good evidence to suggest this is safe and effective?” she said.

She and others, including the F.D.A. in the emergency authorization itself, have said that existing data — from the Mayo Clinic and other non-randomized studies — cannot replace rigorous trials that will more definitively indicate whether and in what groups of patients the treatment is effective. On Monday, the chief scientist for the World Health Organization, Dr. Soumya Swaminathan, said at a news conference in Geneva that only a few of these convalescent plasma trials had reported findings, and that the trials had been relatively small. “The results in some cases point to some benefit but have not been conclusive,” she said. “At the moment it’s still very low-quality evidence.”



Source link Nytimes.com

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