The U.S. Food and Drug Administration will permit emergency use of convalescent plasma as a treatment for COVID-19, a decision that came after President Donald Trump repeatedly criticized the agency and accused it of slow-walking the action to harm him politically.
Trump revealed the FDA's decision Aug. 23 from the White House, with the agency's commissioner, Stephen Hahn, and Health and Human Services Secretary Alex Azar.
White House Chief of Staff Mark Meadows said the decision to grant an emergency use authorization, or EUA, for convalescent plasma in treating COVID-19 patients "should have been made several weeks ago."
"It was a fumble by a number of people in the federal government that should have done it differently, and having been personally involved with it, sometimes you have to make them feel the heat if they don't see the light," Meadows said Aug. 23 on "Fox News Sunday."
Meadows made similar remarks on ABC's "This Week."
Meadows was referring to an Aug. 22 tweet by Trump in which he called the FDA a "deep state" agency, which was "making it very difficult for drug companies to get people in order to test the vaccines and therapeutics."
Trump accused the FDA of delaying decisions on products until after the Nov. 3 U.S. election — an allegation he also made Aug. 19 specifically about plasma therapy after a report by The New York Times that top scientists at the U.S. National Institutes of Health had objected.
No randomized trials
Convalescent plasma is considered an experimental therapy and is not approved by the FDA.
Plasma is the liquid part of blood. People who recover from infectious diseases, like COVID-19, may have antibodies in their blood capable of fighting the virus.
The product is already available under an FDA-monitored, U.S. taxpayer-funded expanded access program run by the Mayo Clinic.
Mayo said about 72,200 people have been infused with the plasma therapy as of Aug. 23.
There are no data from randomized clinical trials available that show convalescent plasma is successful in treating COVID-19.
Azar and Hahn claimed regulators had observed a 35% improvement in survival in COVID-19 patients who received convalescent plasma, but neither of the officials nor the FDA provided the data or the source of that information.
On Aug. 14, Mayo reported that the seven-day mortality rate was reduced in patients transfused within three days of COVID-19 diagnosis compared with those who received the therapy four or more days after diagnosis — 8.7% versus 11.9%. It said similar findings were observed in 30-day mortality — 21.6% versus 26.7%, respectively.
The authors of the report, which was posted online but has not been published in a peer-reviewed medical journal, concluded the pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 for seven days and 0.77 for 30 days compared to low antibody level plasma units.
The Mayo expanded access data means three COVID-19 patients were alive at seven days and five at 30 days with convalescent plasma.
Experts condemned Hahn's and Azar's claims as manipulating science.
"Without a placebo comparator, cannot say there is a 35% improvement," Ed Livingston, the deputy editor of clinical reviews and education at the Journal of the American Medical Association, tweeted. "Lots of reasons comparing high to low antibody levels in the serum could yield spurious results."
"Subgroup analyses of retrospective studies gives cherry picking a bad name," Jeremy Samuel Faust, an emergency physician at Brigham and Women's Hospital and an instructor at Harvard Medical School, added. "Breakthroughs come from randomized controlled trials, not cherry picking subsets of existing datasets and finding one promising finding amongst a sea of disappointment."
Patti Zettler, associate professor of law at The Ohio State University, noted that by definition, expanded access programs are not studies.
"The primary purpose is to treat patients, not study the safety and effectiveness of the intervention," Zettler told S&P Global Market Intelligence. "Sometimes expanded access does produce some evidence, but it is not designed to do so and is not a study."
Robert Califf, who served as FDA commissioner at the end of the Obama administration, said well-designed, randomized controlled trials are needed to be sure about the effectiveness of convalescent plasma use in treating COVID-19.
"Let's get the trials done and if the results are lifesaving, let's make it standard of care, thus benefitting hundreds of thousands to millions," Califf tweeted. "If not, we can avoid the huge expense and effort and keep looking for best treatments."
Congress created the EUA process in 2004 to grant preapproval use of medical products when the secretary of the U.S. Department of Health and Human Services declares a public health emergency.
Azar declared such an emergency on Jan. 31 for COVID-19, though it was not made official until Feb. 4. Public health emergencies must be renewed every 90 days — an action most recently taken July 23.
Granting an EUA provides liability immunity to certain individuals and entities against any claim of loss caused by, arising out of, relating to, or resulting from the manufacture, distribution, administration or use of medical countermeasures, except for claims involving willful misconduct.
The EUA may also allow more commercial distribution and permit manufacturers of plasma products to more easily recoup the costs, said Scott Gottlieb, who ran the FDA for Trump for less than two years before Hahn took over.
"The bottom line is it's widely available right now, patients are getting it," Gottlieb said Aug. 23 on CBS' "Face the Nation."
But while the EUA may enable easier access to the plasma therapy in certain settings, the gains for patients have only been shown to be incremental, Gottlieb said.
"Incremental gains are important here, but we need to view it for what it is," he said.
Gottlieb called plasma therapy "weakly beneficial in the setting of this treatment."
"I think some people wanted to see more rigorous data to ground" the FDA's EUA decision, the former agency chief said.