- A panel of advisers for the National Institutes of Health was not convinced convalescent plasma should be used to treat COVID-19, a recommendation that appears to conflict with a controversial decision by the Food and Drug Administration last week to issue an emergency authorization for the blood-derived treatment.
- The panel, made up of doctors from across the country and government officials, reviewed the same data cited by the FDA, but concluded it to be "insufficient" to recommend "either for or against the use of convalescent plasma for the treatment of COVID-19."
- The recommendation isn't without precedent; the same panel cautioned against using hydroxychloroquine in treating coronavirus disease three weeks after the FDA cleared emergency use of the malaria pill. But the dissent is still notable, particularly after high-ranking NIH officials reportedly resisted the FDA's decision to authorize convalescent plasma.
The FDA's emergency authorization for convalescent plasma, which is made from the donated blood of recovered COVID-19 patients, would likely have been controversial in any case.
But announcement of the decision, made by FDA Commissioner Stephen Hahn at an Aug. 23 press conference with President Donald Trump and Health Secretary Alex Azar, drew sharp criticism for exaggerating the potential benefits of the treatment.
At the conference, held one day after Trump attacked the FDA for slowing access to coronavirus drugs, the president, Azar and Hahn claimed treatment with plasma would reduce deaths from COVID-19 by 35%.
That number appears to have been based on a small subset of about 1,000 patients in an expanded access program run by the Mayo Clinic, which the FDA relied heavily upon in authorizing plasma treatment. But data from the program, which has involved more than 90,000 patients to date, did not compare plasma to placebo, nor did the overall results support anywhere near such a dramatic benefit.
Hahn also misspoke, saying the administration of plasma would save the lives of 35 people for every 100 who are ill with COVID-19 — a statistic that both significantly overstates the mortality rate from the disease, and oversells plasma's benefits.
The FDA chief later apologized on Twitter and said criticism of his remarks was justified — an acknowledgement that appears to have resulted in a shake-up of public relations officials at the agency.
The bar for emergency authorizations is significantly lower than that of a regular drug approval. They can only occur in the context of a public health emergency, and must clear a drug to treat a serious or life-threatening disease for which there are no available alternatives.
In the FDA's decision memo on convalescent plasma, the agency only determined the treatment "may be effective," and judged that the known and potential benefits outweigh the known and potential risks. An authorization does not mean, as the FDA stated, that plasma should be considered a new standard of care.
Typically, however, researchers and doctors still want to see some supportive data from a randomized clinical trial, the gold standard of scientific research. While researchers have launched dozens of studies testing plasma in COVID-19, there's no evidence from a large, well-controlled trial comparing the treatment to placebo that supports a significant benefit.
The NIH panel pointed to that lack of data, noting "uncertainty remains about the efficacy and safety of convalescent plasma due to the lack of a randomized control group and possible confounding in the Mayo Clinic's [program]."
Both the panel and the FDA called for continued study of plasma in randomized, controlled studies. Conducting those studies may now be more difficult, however, now that plasma is authorized and can be distributed across the U.S. for use in treatment.
One of the chairs of the panel is H. Clifford Lane, the deputy director for clinical research and special projects at the National Institutes of Allergy and Infectious Diseases. According to The New York Times, Lane, alongside NIAID Director Anthony Fauci and NIH Director Francis Collins, had urged the FDA to hold off on authorizing plasma for COVID-19 until more data was gathered.
In a Tweet late Tuesday, Collins said he was "surprised by the media uproar" over the panel's recommendation, adding that he views the guidelines as mirroring the FDA's emergency authorization.
Should more data emerge, the FDA can revise or revoke its decision, as it did with hydroxychloroquine. But the FDA's early clearance of plasma carries more significance as the agency may soon have to decide on whether to authorize a coronavirus vaccine before clinical testing is complete.