FDA made right call on plasma treatment

Ordinarily, a new medical treatment is approved only after at least one large-scale, randomised controlled trial shows it to be effective without being harmful. Yet at times — and notably during epidemics — evidence can mount that a treatment is safe and effective before we have that final evidence. We think this is the case with Covid-19 and convalescent plasma.
The Food and Drug administration (FDA) gave a limited, emergency authorisation for the inpatient use of convalescent plasma, which is donated by people who have recovered from Covid-19. The decision set off a media firestorm, with politicians, public-health officials and medical professionals insisting that the Donald Trump administration was playing politics with science.
But as two authors of a study the FDA relied on heavily in making its decision, we believe that there are several convincing reasons that going ahead now with emergency use of the treatment is the right way to save lives until the large randomised trials now being mounted can be completed.
First, human plasma is used as a treatment all the time in clinical medicine. Plasma is obtained from donors and distributed by blood banks, and about two million units are used annually in the US Convalescent plasma for patients with Covid-19 differs from ordinary plasma only in that it comes from individuals who have recovered from the disease, and is therefore expected to be rich in antibodies to the Sars-CoV-2 virus.
Second, the largest study to date, done by the Mayo Clinic and colleagues, has produced firm evidence based on the first 20,000 treated patients, that acute side
effects were extremely rare. Covid-19 plasma has proved as safe as regular plasma.
Third, an especially a strong piece of evidence has recently emerged from the most recent Mayo Clinic study, and it was this new finding that compelled the FDA to act. Blood banks have a policy of retaining a small amount of plasma or serum from each unit they provide to hospitals, to allow testing of the sample in case an unexpected infection or other complication is found in the recipient. This practice permitted researchers to measure the amount of antibody provided to several thousand transfused Covid-19 patients, and it showed that mortality in recipients was directly and strongly related to the amount of antibody in the transfused plasma.
This finding of a clear dose-response relationship is as close to the result of a randomised trial as could be designed. The amount of antibody in plasma was unknown to anyone when it was provided to the patient. In effect, patients were assigned, in a process akin to randomisation, to different levels of antibody, and the results showed that the active principle in convalescent plasma — the antibody level — was effective in reducing mortality. (We do not yet know whether recipients of plasma with lower levels of antibody benefited or might still have fared better than if they had received none.)
This finding was posted on the MedRxiv server, which publishes preliminary reports of work that has not been certified by peer review. (It had nearly 40 co-authors, including ourselves.)
We know that scientists at the FDA’s division of biologics reviewed this data — and additional data requested from Mayo — before last weekend’s approval
announcement. We find no suggestion of unreasonable delay or unreasonable haste in the FDA action. The political overlay that science must sometimes endure can be very misleading.

—Bloomberg