Mayo Clinic investigators and supporting team members were “puzzled” by federal actions this week involved with at least the temporary halting of the convalescent plasma program. TrialSite summarized a New York Times article announcing that key federal research players, including NIH Director Dr. Francis S. Collins and NIAID Director Dr. Anthony S. Fauci, actually intervened with the U.S. FDA to at least temporarily halt the Emergency Use Authorization (EUA) for ongoing treatment of hospitalized patients infected with SARS-CoV-2, the virus behind the COVID-19 pandemic. Michael Joyner overall has led a tremendously successful program. In fact, the national program, self-organized and governed, has outperformed federal NIH-sponsored clinical trials when it comes to recruiting ethnic minorities and women. Could there be some conflict growing between federal research agencies and major academic medical centers out in the field?
John Paul Scott writing for the Superior Telegram recently provided an interesting perspective on this state of affairs. For those that don’t follow these programs closely, it can become confusing. TrialSite provides a breakdown in the hopes of providing a little more clarity.
What is the Mayo Clinic program?
Led by Dr. Michael Joyner, the Mayo Clinic launched the national convalescent project along with 34 initial institutions from 17 states. By April 1 of 2020, the effort included over 100 researchers and 40 large hospitals in 20 states. TrialSite wrote about this effort and received hundreds of communications from doctors seeking to become investigators, COVID-19 patients (or their family members) seeking help and donors interested in finding locations.
How big has this program become?
The Mayo Clinic National Convalescent Plasma program has grown exponentially reports journalist Mr. Scott, growing to 8,000 doctors in 3,000 hospitals serving 100,000 enrollees, with 70,000 to 80,000 transfusions already completed.
The NY Times article suggested “unnamed health officials” expressed concerns the Mayo program competes against other important studies. Did it threaten other studies?
Perhaps there have been rumblings that the Mayo Clinic national program has monopolized clinical trial subjects, but Dr. Joyner, again the lead, commented, “That’s a false dichotomy.”
What is convalescent plasma?
It derives from the blood of donors who have recovered from COVID-19. Those who have recovered are “antibody-rich” and hence the idea is that if transfused to present COVID-19 patients it can boost their immune system with antibodies to fight the novel coronavirus. Present Donald Trump has been on the record that it’s a “beautiful ingredient” in the veins of people who have survived COVID-19.
What happened this week?
As reported by the New York Times by Noah Weiland, Sharon LaFraniere, and Sheri Fink, the U.S. Food and Drug Administration was nearing readiness to issue an “emergency use authorization” for convalescent plasma as a COVID-19 treatment but federal researcher heads, Collins and Fauci, blocked the effort, suggesting that the existing data for efficacy wasn’t strong enough, reported two senior administration officials. The New York Times article suggested that federal officials were concerned that the findings thus far from the Mayo program were not sufficiently strong to justify an EUA.
But conflicting messages were sent out to the market?
Moreover, H. Clifford Laine, clinical director with National institute of Allergy and Infectious Diseases suggested that the emergency approval could actually still be issued “in the near future” giving what could be considered a positive signal.
What’s the benefit of the FDA issuing an EUA?
An EUA helps expand the availability of convalescent plasma to everyone that could use it across the nation.
Does the action halting the EUA impact the current Expanded Access Program?
No. Michael Joyner was quoted in the local press that “We have an expanded access protocol which continues.” Dr. Joyner serves as the Principal Investigator on behalf of the Mayo Clinic Convalescent Plasma Program.
Was Mayo ever asked to run a clinical trial?
No, Joyner was quoted by the Superior Telegram. In fact, Wright from the Mayo said that Mayo asked twice if the FDA wanted them to transition to a randomized controlled trial. The FDA suggested they just finish the convalescent plasma initiative.
Did Dr. Joyner anticipate an FDA greenlight to EUA?
What’s Dr. Joyner’s Position?
This kind of thing happens all the time, noting, “The FDA delays things for additional data all the time.” He noted “Even though this is COVID, this is not unusual.” He continued, “The fact that there is discussion amongst the various senior scientists inside the department of Health and Human Services is not unusual. We’re just doing our duty trying to get the best data we can under the circumstances of the pandemic.”
Other Mayo Clinic Perspectives
Dr. Scott Wright, another Mayo plasma program clinical researcher, doesn’t think there is a material delay. He also suggested that the Mayo program wasn’t competing against other NIH-funded studies, commenting, “All these people are being treated in places where there would never be a trial. Places like Laughton, OK.” He emphasized the clinical trials are conducted in large metropolitan hospitals.
Mayo Program Recruiting more Diverse Participation than Feds?
Yes. Generally, according to the recent local press, the Mayo program’s patient breakdown includes 20% Black over 35% Hispanic, 10% Asian, and 40% women, which means the Mayo-led, national program has performed better than Operation Warp Speed when it comes to recruiting a diversified COVID-19 patient pool.
Why can’t the Mayo program results be considered evidence?
Because the program lacked a comparator group. It can’t prove that convalescent plasma is effective based on the lack of randomized controlled trial.
Why wouldn’t HHS Consult with Mayo prior to Making their move in the FDA?
Not certain but it definitely is similar to other tensions exhibited as of late, evidencing the federal research apparatus’ insecurity for whatever reason.
Didn’t Dr. Fauci support the actual changing of the Remdesivir (Gilead) endpoint measurements just two weeks prior to the end of the trial—in a bid to ensure success?