A deadly pandemic isn't the time for leading U.S. health agencies to disagree on data and treatment benefits, but that's the situation playing out as new COVID-19 treatment guidelines from the National Institutes of Health (NIH) rejected the FDA's word on convalescent plasma.
Days after the FDA granted plasma a controversial emergency authorization, NIH experts concluded there are “currently no data from well-controlled, adequately powered randomized clinical trials that demonstrate the efficacy and safety” of the treatment in COVID-19. Plasma "should not be considered" standard of care for treating COVID-19 patients, the agency said.
The FDA authorized plasma based on observational data from an expanded access program at the Mayo Clinic, not a controlled clinical trial. And in doing so, the agency relied on an analysis comparing outcomes in patients who received plasma with high titers of SARS-CoV-2 antibodies compared with those who received plasma with low titers.
For patients who weren’t intubated, 11% of patients who received plasma with high titers died within seven days, compared with 14% who received low antibody titers, the NIH said. The data suggest plasma with high titers “may be beneficial” for those patients, but “uncertainty remains," NIH experts said. Plus, they said, it remains difficult to detect whether plasma has high or low titers.
In all, there’s “insufficient data to recommend either for or against” the treatment option at this point, the NIH experts said, and randomized trials will need to determine safety and efficacy.
The treatment guidelines unequivocally rejected the characterization of plasma as a “historic breakthrough” or “major advance," statements made by President Donald Trump and Department of Health and Human Services Secretary Alex Azar, respectively, at a briefing where they announced the FDA's emergency nod.
FDA Commissioner Stephen Hahn. M.D., triggered controversy with his own misleading statements at that briefing. Convalescent plasma is associated with a “35% improvement in survival,” Hahn said, which experts quickly pointed out was incorrect. The commissioner later tried to walk the statement back, but health experts still argued there’s not sufficient evidence to claim any survival benefit, period, without controlled trials.
The disagreement between the NIH and FDA comes as COVID-19 continues to spread in communities nationwide. And it comes as former NIH Director Harold Varmus, M.D., plus Rockefeller Foundation President Rajiv Shah, M.D., wrote a New York Times op-ed calling for Americans to "ignore the CDC" in the wake of new, narrower testing guidelines.
The controversy in recent weeks hurt the FDA’s reputation at a critical time, experts said. Influential doctors blasted the agency's move on social media, and many worried the FDA would use similar decision-making processes when reviewing potential vaccines.
In response to the debacle, Medscape editor-in-chief and prominent physician Eric Topol called on Hahn to “tell the truth or resign.” In an open letter, Topol said the agency’s handling of the hydroxychloroquine saga—plus convalescent plasma and the latest remdesivir emergency use authorization—show Hahn’s “willingness to deviate” from the FDA’s “bedrock premise” of relying on “accurate, science-based information.” He called on the commissioner to hold a press conference and explain the plasma announcement and any pressure that went into it. Otherwise, he said, Hahn should resign.
Surveys have shown the public is already worried about vaccines moving too fast through the pipeline, and doctors say a fully transparent approval process is needed to win people's trust—and persuade them to be vaccinated when the time comes.