Last week I used two blog posts to examine the decision by the Food and Drug Administration (FDA) to provide an emergency use approval (EUA) for the treatment of COVID-19 with convalescent plasma. This therapy theoretically uses antibodies from the blood of recovered COVID-19 patients to neutralized and inactivate the SARS-CoV-2 virus in the bloodstream of patients with acute COVID-19 infection. This could suppress the viral infection and improve patient recovery.
While some preliminary data suggests that there is potential benefit from this approach, there is no definitive evidence showing that it is of true clinical value in treating COVID-19. My first blog post pointed this out as the reason the FDA had rejected this therapy. Subsequently, my second post tried to define why the FDA had reversed itself.
There were several unusual aspects of this EUA approval process. As mentioned above, the FDA initially appeared not to approve the therapy then reversed itself last Monday without additional information or studies. It also appeared that National Institutes of Health (NIH) scientists were strongly against providing the EUA approval. Finally, the FDA Director’s public comments about the effectiveness of this therapy were inaccurate, and he subsequently withdrew them and apologized.
Yesterday, in an incredibly unusual step, the NIH issued treatment guidelines for COVID-19 that took specific exception to the EUA for convalescent plasma. NIH and FDA are both federal agencies in Health and Human services, one research directed (NIH) while the other regulatory (FDA). While they overlap on most biomedical topics, there has always been a line of demarcation where the two deferred to each other on their specific duties. This is the first time I can remember such an open disagreement on a regulatory matter.
The NIH panel stated that based on the available evidence, they had determined the following:
- There are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19.
- Available data suggest that serious adverse reactions following the administration of COVID-19 convalescent plasma are infrequent and consistent with the risks associated with plasma infusions for other indications. The long-term risks of treatment with COVID-19 convalescent plasma and questions about whether its use attenuates the immune response to SARS-CoV-2, making patients more susceptible to reinfection, have not been evaluated.
- Convalescent plasma should not be considered standard of care for the treatment of patients with COVID-19.
- Prospective, well-controlled, adequately powered randomized trials are needed to determine whether convalescent plasma is effective and safe for the treatment of COVID-19. Members of the public and health care providers are encouraged to participate in these prospective clinical trials.
- The Panel will continue to evaluate emerging clinical data on the use of convalescent plasma for the treatment of COVID-19 and will update the Convalescent Plasma section of the Guidelines in the near future.
If there is common ground in this interagency dispute, it is that more data is needed. This means that prospective, well controlled and randomized trials are necessary before any assessment of the value of plasma transfusions can be made. Everything else in this debate is meaningless.
As I said in my prior posts, the real concern with this is that time and money may be wasted on an ineffective therapy that competes for development with effective treatments, thus delaying drug development and costing lives.