On Wednesday, The New York Times reported that in light of the current lack of efficacy data, the FDA has put plans in place to issue an Emergency Use Authorization to treat anyone with Covid-19 with convalescent plasma, even outside the Mayo led program. (In an email, Anand Shah, Deputy Commissioner for Medical and Scientific Affairs at the FDA) wrote: “Per policy, we are unable to comment on whether or not we will take action regarding emergency use authorization for recovery time plasma. and will take a decision at the appropriate time. ”)
What at the beginning of the pandemic looked like a rare bright spot – that a classic treatment used in pandemics for the past century may also prove to be effective in this, and provide a relatively simple stopgap before monoclonal antibodies and vaccines – now seems dimmer . It’s not that it doesn’t work. It’s worse than that: Because of mistakes in the system of how science is done, no one knows.
This is not so things had to happen. Earlier this year, when I spoke to Joyner, he told me about the three trials she hopes to run. Back in March, Joyner saw work validating the use of plasma as a bridge to more specific therapies – hyperimmune globulin, monoclonal antibodies that attack a carefully selected part of the virus, and ultimately vaccines that build a physical response, ideally a permanent.
It made sense. Plasma has been used for decades. Health workers tried it against MERS, against the first SARS, against Ebola. More recently, it published a small randomized clinical trial of plasma on Covid-19 in China JAMA in June – just 103 patients – stopped early, but showed signs of improvement. Another small RCT in the Netherlands, published in July as a preview, did not show plasma efficacy, but it did respond that dose timing was key.
A Mayo spokesman declined to make Joyner available for an interview this week, but he did said on Twitter that funding sources turned down his group’s trials, that they were more interested in pursuing hyperimmune globulin, a more specific type of blood-derived immunotherapy. Another researcher, who was involved in building the extended access program, also tells me that she opposes her efforts to run randomized trials from the beginning. “We set up these test subjects, and we approached multiple federal agencies and private funders to get these tests started immediately, and we were actually not very lucky with that,” says Jeffrey Henderson, a physician and researcher at Infectious Diseases at Washington University St. Louis. ‘We had all these threads in the hopper. We were ready to ride the first wave. We thought we would not have enough to give to anyone anyway, let’s shed tears. We just could not get any traction. The studies we are coming out of now are not the studies we wanted to do. They are the people who make the most of the situation. ”
I asked representatives of the National Institutes of Health if they discussed the studies that Joyner proposed, but they did not respond. Henderson told me that the Mayo-led consortium approached the Gates Foundation, a major funder of medical research, and were repatriated in the same way. A spokesman for the Gates Foundation said the foundation had never received a formal proposal from any kind of Joyner group – and that the foundation is more focused on funding research into hyperimmune globulin. It does not require a relatively complex infusion, as plasma does, it is more shelf stable, and may be more targeted than treatment.
The extended access program could in one sense have been a victim of its own success. The planners initially expected to reach perhaps 300 hospitals. Instead, they ended up with a network of more than 2,700, with 14,000 doctors. The team expected to enroll 5,000 patients, a mark they passed on within a few weeks. The vast majority sat in hospitals that had no infrastructure or experience with clinical trials, and it would not be expected that they perform. Initially, the FDA expected a smaller scale program for expanded access that would be one of three ways people would get a convalescent plasma. The other two would be either through an emergency Investigational New Drug (or IND) license that the agency also approves (allowing doctors to prescribe plasma that they received from other sources), and randomized clinical trials. Patients would receive the help they desperately needed, and the evidence would soon come to naught.
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