Emergency plasma authorization sparks concern for those leading charge on treatment

By SASHA PEZENIK, ABC News

(WASHINGTON) — In the high-pressure push to combat COVID-19, two things have become abundantly clear: we need effective treatment and we need further data to inform our findings.

Sunday evening, the FDA issued what was a long-expected emergency authorization for one of the treatments most eyed with high hopes — convalescent blood plasma. President Trump, has even recently been touting the treatment as a “powerful therapy” with an “incredible rate of success.”

While some doctors welcomed the authorization, others tasked with spearheading the ongoing clinical study of convalescent plasma’s efficacy tell ABC News that this latest green light may make their work more difficult.

“This authorization doesn’t make a lot of sense to me — it basically says we’re approving it on no data,” Dr. Hollis O’Neal told ABC News, whose team at LSU Health Sciences Center in Baton Rouge, Louisiana, has joined the newly-announced clinical trial through Vanderbilt University. “It complicates the issue and makes it more difficult to recruit on both ends. You have to keep the data clean here or there’s just no way to interpret it. It puts everyone in a difficult position as far as being able to do this study that we all believe is necessary to do.”

The concern is that the widespread use of plasma treatment will introduce confounding variables to randomized, controlled clinical trials — what’s understood as the scientific “gold standard.”

The FDA said more than 70,000 patients have been treated with convalescent plasma so far and preliminary results have been somewhat promising with mortality rates slightly reducing in hospitalized patients treated with it earlier on.

Harvested antibodies from those who have recovered from COVID-19 are now authorized for use on the sick but that permission could prevent scientists from knowing how well, or even if, it actually works.

“It could really violate the integrity of the trial,” O’Neal said. “We could still do the study, but it would create selection bias, or we would need another mechanism to control for potential use of plasma as standard care.”

“The @US_FDA’s emergency use authorization just makes it harder to conduct placebo-controlled, randomized clinical trials to figure out if it works,” Dr. Céline Gounder, infectious diseases specialist at NYU Langone Health, tweeted in response to Sunday’s announcement.

Clinical trials for convalescent plasma have already faced many obstacles and recruiting volunteers is not an easy task, especially amid a global health crisis, when control trials require a placebo group while there is desperate demand for actual treatment and finding anyone willing to risk taking a placebo poses a high hurdle.

However, not everyone agrees the authorization steepens the scientific climb.

“Clinical trials in hospitals were already very difficult to do,” Dr. Arturo Casadevall, Johns Hopkins Chair of Molecular Microbiology & Immunology, told ABC News. “Doing clean, randomized control trials is very, very hard in the middle of a pandemic. You almost have to have put all the pieces in place in advance. But there is a lot of evidence now that this is reducing mortality. It may not be as definitive as you would want — but at least we have treatment. And that, we need now.”

Thus, the debate fundamentally becomes one over how much time we have — and how to use it — in pursuit of a cure.

“It’s a nuanced argument and the FDA has been struggling with this for months,” Casadevall continued. “I think this makes it a lot easier for our patients in hospitals in in places that don’t have a lot of resources. It’s been shown to work and something that here could probably help people. So I would ask you — what would you do?”

Unquestionably, medical experts say we need good treatment and we need it fast. But it’s a matter of what gets introduced and when that makes a difference in the hunt for the definitive data that top federal officials have consistently called for.

Now with this plasma treatment even more widely available, those already not inclined to participate in placebo studies may find it even less appealing.

But when asked about his concern over issuing an emergency authorization now that may inhibit researchers’ ability to conduct clear, clean clinical trials, and if it will be harder to avoid introducing confounding factors to getting further data, FDA Commissioner Dr. Stephen Hahn expressed hope, telling ABC that, ideally, this would in fact encourage more people to participate.

“We all can use this as an opportunity to encourage people to participate in clinical trials for all therapeutic and vaccine agents in this time of crisis — because it’s so important, and it does a service to everyone,” Hahn said.

In an op-ed Sunday night, former FDA commissioner Scott Gottlieb wrote that the plasma authorization now comes despite recent concerns from public health leaders about the lack of evidence.

“The decision would have a stronger foundation if patients had participated in a randomized study that looked at whether patients who received plasma fared better than those who didn’t,” Gottlieb wrote. “The pressure to find effective treatments for COVID-19 is enormous. All the more reason to rely on FDA expertise to steer the focus toward the most promising options and get patients the clear evidence, and effective treatments, they deserve.”

“This makes our work a little harder. But it doesn’t make it impossible,” Dr. Todd Rice, one of the Vanderbilt clinical study’s leaders told ABC. “I’m so excited about doing a study because I think the science behind this — and the early data — are encouraging. So — as they said announcing the authorization — it’s suggestive of benefits. And it’s encouraging. We want to see treatment. I agree with a lot of that. I don’t think they’re strong enough data yet – to definitely give it to everybody – which is why it’s important to study it: is this something where we should be putting a ton of eggs in the basket?”

The “elephant in the room,” Rice says, is the very language in the emergency authorization itself:

“Given that the clinical evidence supporting this EUA was not obtained from prospective, well-controlled randomized clinical trials,” a fact sheet for healthcare providers on the authorization says, more randomized clinical trials are needed, adding, “convalescent plasma should not be considered a new standard of care for the treatment of patients with COVID-19.”

“To me — and to the group that’s doing these trials — that means it’s urgent that we get to an answer on this,” Rice said. “There’s more pressure now. But to be honest — we were going to do this anyway — it just means we need to comb over our data all the more, every step of the way.”

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