NIH Calls for More Randomized COVID-19 Trials for Convalescent Plasma

The National Institutes of Health (NIH) on Wednesday said that there’s currently not enough data to say if convalescent plasma should be recommended or rejected as a COVID-19 treatment, doubling down on its previous advice to the FDA to delay Emergency Use Authorization (EUA) until more evidence is available.

More prospective, well-controlled, randomized trials are necessary to make a call on convalescent plasma as a coronavirus treatment, the NIH’s COVID-19 Treatment Guidelines Panel said in response to the FDA’s Aug. 23 emergency authorization, adding that convalescent plasma should not be considered the standard of care for treating COVID-19 patients.

The panel reviewed the evidence from both published and unpublished data on the potential treatment — including the FDA analyses that supported the agency’s recently issued EUA — and said it has not seen any data from randomized trials that show convalescent plasma is a safe and effective COVID-19 treatment.

“There are currently no data from well-controlled, adequately powered randomized clinical trials that demonstrate the efficacy and safety of convalescent plasma for the treatment of COVID-19,” the expert panel said. “There are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19.”

Although data showed infrequent serious adverse reactions that were similar to risks associated with plasma infusion for other indications, the risks of long-term use for treating COVID-19 have not been evaluated, and it’s not yet clear if long-term use could reduce patients’ immune response to the virus and make them more vulnerable to reinfection, the panel warned.

The FDA’s authorization for convalescent plasma was granted based on hospitalized patient data from the Mayo Clinic’s expanded access program and did not use data from controlled clinical trials. While the expanded access data suggested that convalescent plasma with high antibody titers could benefit patients not on intubation, “uncertainty remains about the efficacy and safety of convalescent plasma” because there was a lack of a randomized control group and “possible confounding” in the program, the panel said.

NIH Director Francis Collins attempted to calm the intense media coverage of the panel’s treatment guidelines as a public rebuke of the EUA, clarifying that the FDA’s authorization also advises against using convalescent plasma as the new standard of care for COVID-19 and notes that more randomized trials need to be conducted.

“[The] guidelines mirror [the] EUA: possible benefit, seems safe, randomized trials needed,” Collins said via Twitter. “No news here.”

The director had previously said that studies of convalescent plasma in hospitalized coronavirus patients showed “promising results” and were being further evaluated in randomized control trials.

Widespread speculation persists that the FDA may fold to political pressure from the Trump administration to speed up approval or emergency authorization for a COVID-19 treatment or vaccine before the Nov. 3 presidential election, although FDA Commissioner Stephen Hahn has repeatedly denied that the agency’s evaluations are anything but rooted in science and has said that he will resign rather than give in to pressure.

The commissioner recently drew widespread criticism from the scientific community for his misrepresentation of convalescent plasma’s effectiveness during the White House announcement of the agency’s EUA, but he apologized for the error within days (DID, Aug. 26). — James Miessler