This weekend, the Food and Drug Administration granted emergency clearance to convalescent plasma, a treatment in which blood from patients who recovered from Covid-19 is used to treat those who had the disease. The decision is controversial, as are the circumstances around it. STAT senior writers Matthew Herper and Adam Feuerstein sat down together to gather their thoughts. Here is their conversation.
Matt Herper: So for those just back from a tour of Jupiter’s moons, last night the FDA granted emergency use authorization of convalescent plasma to treat patients with Covid-19. Trump characterized the decision as a major breakthrough. FDA Commissioner Stephen Hahn, who joined him at a news conference to announce the decision, backed him up — but he also misspoke, claiming that giving plasma would help 35 out of 100 people treated.
Adam Feuerstein: Misspoke is being kind. Hahn grossly mischaracterized the benefit of convalescent plasma on Sunday night. I’ll just quote him here: “A 35% improvement in survival is a pretty substantial clinical benefit. What that means is — and if the data continue to pan out — 100 people who are sick with Covid-19, 35 would have been saved because of the administration of plasma.”
The data don’t show that!
Matt: That number should be at best 5 out of 100 people. To my eye, it’s more like 3 out of 100 people. And all that is from subgroups of an observational study, so it should be taken with a grain of salt.
Researchers didn’t compare patients who got plasma to a control group. They compared those who got the drug early to those who got it late, and between high levels of antibodies in the plasma and low ones. For the main subset in the study, which was led by the Mayo Clinic, mortality at seven days was 11% for those who got lots of antibodies, versus 14% for those who got few. That’s three out of 100 — again, with a grain of salt.
Adam: I’ll repeat here what I said on Twitter last night. I’ve spent 20 years listening to — and writing about — biotech CEOs making nonsensical, inflated claims about the benefit of their drugs. It was weird and disconcerting to hear the FDA commissioner do the same.
Hahn could have made a convincing case for granting an EUA to plasma without hyping the data. He’s an oncologist. He knows better.
Matt: That’s exactly it. There is an argument for emergency use — that patients were getting this, but access was spotty and we need to decrease paperwork. Even then, it would be controversial.
I’ve watched the FDA be the steward of high scientific standards in medicine for a long time. I still remember the nuance in the discussions around Vioxx. The agency gets things wrong sometimes. But it feels worse for it to be sloppy. And that’s without bringing politics into it.
Adam: I am sincerely worried about the FDA’s independence. Trump wanted convalescent plasma approved even though the supportive evidence was weak, and Hahn made it happen for him. That’s bad, particularly with the evaluation of Covid-19 vaccines looming right before the election.
Matt: Everyone is worried about that. Some really prominent researchers — Ezekiel Emanuel springs to mind — have said they are concerned the administration could try to rush a vaccine. As we were talking, Steven Nissen at the Cleveland Clinic called me to say he’s worried about exactly that. “The process is there because the process has a historical record of working in the public interest,” he said. It does.
Which is exactly what’s wrong with the FDA putting out a press release saying this approval is “Another Achievement in Administration’s Fight Against Pandemic.” Even worse, there’s that tweet from the president Saturday, saying that the FDA was slowing down clinical trials for Covid patients because the agency is part of the “deep state” and it wants to hurt his re-election chances. Axios has reported that Peter Navarro was yelling “deep state” at the FDA earlier this week.
That kind of talk is going to make people more skeptical of an eventual vaccine. And, assuming the FDA does its job on vaccine review, that’s exactly what we don’t want.
Adam: I spoke to some current and former FDA employees over the weekend. None would go on the record, of course, but they were demoralized and angry about Trump’s insinuation that they were working against the approval of medicines for Covid-19. They were also angry at Hahn for not stepping up to defend them and their work.
Did you notice the FDA staffer charged with reviewing the plasma data had his name redacted from the memo? That was unusual, to say the least.
Matt: I never remember seeing a reviewer’s name redacted before. I’d also add that I have never met an FDA employee who struck me as partisan. A few struck me as people who could never fit in any political party.
It’s definitely possible, with these giant studies that are being run and the number of people getting Covid-19, to develop a vaccine fast. But you need people to really trust the FDA, or many might not take the vaccine.
Adam: Being the FDA commissioner is a political job. But Hahn is also the leader of an essential government agency that employs 17,000 people. Standing up to Trump is not an easy thing to do, but at some point, Hahn has to tell his employees that he has their back, and that he believes in the scientific independence of the people who work under him.
FDA employees deserve to hear that. Americans need to hear it, if they’re going to trust the FDA decision making about medicines and vaccines to treat Covid-19.
Matt: There have been other times where commissioners have had to deal with political pressure and political issues. The controversies over the Plan B morning-after pill going over the counter spring to mind. But this feels different.
Also, let’s not lose sight of the fact that all of this comes from a big failure on the part of the government response: not conducting a convalescent plasma study that can get us a real answer.
We wrote a very optimistic story about convalescent plasma together at the beginning of the pandemic. Would you have believed me then if I’d said we still would not have clear data here?
Adam: As you’ve pointed out numerous times, there have been many missed opportunities to conduct studies that could have yielded answers about Covid-19 treatments. It’s been a serial problem.
Matt: To me, it’s the problem. We should have answers by now on multiple medicines. The best data has come from the U.K. It means we’re at the mercy of this virus.
Adam: Are you worried about the next few months, specifically about how the FDA handles the review of Covid-19 vaccines?
Matt: A lot is at stake. Some reasons for confidence: No company wants to launch a problematic vaccine. The FDA review division is strong. An EUA could be very narrow — give it to nursing home workers, for instance — and still be used as a political win. And, as I said, these studies should give us a lot of safety data. But even if the scientists do everything right, the public health messaging matters, too. And this weekend gave us reason to worry about all of it.
Adam: This country has a serious problem with vaccine hesitancy. Even the whiff of politics into the FDA review process for Covid-19 vaccines could be disastrous.
Matt: This is a conversation about the FDA, so we’re required by law to include a quote from Scott Gottlieb on Twitter.
“I am confident in the science part of the evaluation executed by CBER [Ed: Center for Biologics Evaluation and Research at FDA]. The way the public part was handled will erode precious public confidence. You earn public confidence in small drops and you lose it in buckets.”
That’s the nicest thing anyone can say right now.
Your quote, Matt, should be taken to heart by so many — “Some reasons for confidence: No company wants to launch a problematic vaccine.” On so many levels, that couldn’t be more true.
I also want to say thanks for sharing your perspective here, for pointing out what has happened in the past, and why this is different. I agree with your interpretation of the weak data, but putting that aside, I decided Hahn had to go when he refused to rebuke Trump for making the “deep state” remark. That’s kowtowing, not leadership. How demoralizing for the staff at the FDA! Thanks for providing the excellent pandemic coverage.
First the science: “mortality at seven days was 11% for those who got lots of antibodies, versus 14% for those who got few”. If you are one of the 14 patients who were to die, would you take plasma to be among the 3 who might survive. That is a 20% chance (3 out of 14).
Then the politics: Is 20% closer to 35% or is it closer to 3%? So, the question is, why is STAT taking a side now that is opposite to what was written in March? Bad at math?
Also missing from the piece is the detail that convalescent plasma has been tested on 35,000 patients before the results were submitted to the FDA for evaluation. Read the report for yourself and make your own oppinion: https://www.medrxiv.org/content/10.1101/2020.08.12.20169359v1.full.pdf
Joe: Disregarding all of the criticisms of the data analysis, and the non-randomized patient population, which are substantial (see @EricTopol, etc for these), and taking the data at face value:
At seven days survival probability is 86% for those who got few antibodies (100-14), while survival probability is 89% for those who got many antibodies (100-11). This is not a 35% increase in survival probability. It is a 3% increase in survival probability.
To Not Joe — the criticisms are “substantial” if you believe that we must do NOTHING until we have a double blind randomized control study. WE DON’T HAVE TIME.
There are two ways of thinking here. There is a “traditional” scientific way of constructing experiments with valid premises that can test a falsifiable hypothesis, observe the output, and then write it up.
Then there is the “logical” syllogistic way — in this instance,
(1) people who get sick and recover from Covid have antibodies in their plasma
(2) Infusing plasma is extremely low risk for patients who receive it
(3) infusing plasma from recovered patients with antibodies into sick Covid patients may have therapeutic effects for those sick patients
When faced with a pandemic, you do the logical thing first…and do the experiments later, assuming you have the opportunity, which you may not.
One more comment: Matt & Adam have been doing a great job for years & I appreciate what they do. Thanks, Matt & Adam.
This is horrible. Politicians should stay out of the FDA. We need to know that the FDA’s judgement & decisions can be trusted. Lives depend on it.
Really? Like its judgment on NOT using protease inhibitors for AIDs patients…a prohibition, that were it not for activists clamoring for their use and succeeding, would have cost an estimated 90,000 lives?
Look, there are good people at the FDA, and most want to do the right thing. But they are HUMAN, and thus it is naive to say that, in such a blanket form, that “we need to know that [their] judgments and decisions can be trusted.”
Like any regulatory agency, their decisions should always be subject to scrutiny and skepticism. Even from politicians.
The minute you let any one entity have what amounts to total power over an important human activity is the day you surrender to despotism.
What about drug companies staying OUT of our FDA.
It’s always been that way.
They had the president promoting plazma a month ago, calling for donations of previous patients. We were all wondering when they were going to start useing it regularly. I imagine, after having him call for donations, the presidents was getting pretty upset with the delays and wanting answers why.
Agree. Stat news has been politicizing from the get go. Just report the news and leave your politics out of it. It degrades your integrity.
You guys kill me…”well, it may be as high as 5 out of 100, but it might be 3…as though that’s effin’ awful and not worth the bother.
Holy crap, do the arithmetic. We may lose 200k people to the virus. Saving 5 our of 100 is 5,000 lives.
Let that sink in for a moment. Ok? Have your paused appropriately? That’s TEN THOUSAND LIVES.
Ok, Ok, I get it…there are a lot of confounding variables in that arithmetic, but here’s the deal. We hang plasma bags on people all the time for a wide variety of reasons. The risks are very very low.
We don’t have time in a pandemic, where we still trying to figure out how the bugger actually works, for placebo controlled double blind studies on potential therapies that are extremely low risk. By the time we figure it all out, the virus will have worked through the population.
Just like hydroxychlorquine. It’s contras are very well known. They are right there on PDR online. Harvey Risch at Yale has already put the lie to the anti-hydroxy crowd.
But nooo… People have to politicize everything because Orange Man Bad.
The FDA is a sclerotic organization where risk aversion rules as the dominant attitude. Recent example? Blindsiding BioMarin. Their mentality is classic…..”yeah….yeah….the stuff works…..but…but…but.. does it work ENOUGH? STOP!!”
At the same time, they are in thrall to NIAID and Fauci who, for some reason that is inexplicable, is considered a “guru” despite his pretty poor predictive track record and his penchant to pontificate about issues and then turn around later and contradict himself.
Trump is absolutely right to pressure them.
After this is also said and done, maybe the FDA should be set up like the Federal Reserve with a committee and chairman and outside HHS and outside political meddling.
Hahn was a senior leader at MD Anderson, he is completely ruining all of his scientific and medical credibility and he will be completely toxic if he jams through a vaccine. He will unable to be employed afterward no biotech or Academic institution will touch him with a 10 foot pole if he does that- he should realize this.
The President’s tweet about the FDA being part of the “deep state” is when Hahn really should have spoken up to., That would have defended the FDA scientists as well as the FDA itself
Has Hahn/FDA issued any press release with a correction as of yet? It’s one thing to make math errors and state options based on them. It’s another thing entirely to stick to your error once it has been pointed out. And far worse to demonize those that only seek the correct math on trial results to be accurately reported.
You want the public to trust the FDA? You think this will cause a distrust? You’ve got to be kidding right? The trust of the FDA has been poor ( at best) for a long time from multiple proven betrayals.