Pushkin from Pushkin Industries. This is Deep Background the show where we explored the stories behind the stories in the news. I'm Noah Feldman. The Food and Drug Administration recently issued an emergency use authorization for doctors to take blood plasma from patients who have recovered from COVID nineteen and use it as a therapy for patients who are sick enough with the disease right now that they find themselves in the hospital. While announcing this authorization, the FDA Commissioner Stephen Hahn said that thirty five out of one hundred of COVID nineteen patients quote would have been saved because of the administration of plasma close quote. This led to an outcry from scientists pointing out that this statement vastly overstated the treatment benefits, criticism that Han later said was in fact justified. So what do we actually know about convalescent plasma as a treatment for COVID nineteen, And, perhaps more important, what does the mess of politicization around this emergency use authorization tell us about what might happen in the future if and when the Trump administration seeks to use an emergency use authorization to introduce a vaccine. Here to discuss these hugely important issues with US is doctor Walid Jelad. Doctor Gelatt is an assistant professor of medicine and health policy at the University of Pittsburgh, where he leads the Center for Pharmaceutical Policy and Prescribing. He has been a frequent and astute commentator on treatment statistics and reality. Well, thank you so much for being here. It's my pleasure. Today. We're going to start with convalescent plasma therapy. And although we're going to talk I think at some length about what is not true of convalescent plasmo therapy, Let's start with what is true of plasma therapy in your view, reading the data that has been made publicly available, what can plausibly be claimed for this therapy in terms of the effect that it could have on people who are ill with covid NT. There are different ways to think about this. I think so one. I think the claim can be made as it was made in the Emergency Use Authorization, which is why the EUA is interesting, And the claim is simply that the totality of the evidence says that it's probably going to help people, and I actually think it is fair to say then, and that's pretty much a low bar for what you need to determine if something is going to be authorized. But the FDA, but I think the totality of evidence, based on what we've seen in animals, in what was in a small randomized trial, and in some of these observational data that was seen from the Mayo clinic, is that it probably help helps to some extent. And that's really all you can say, probably helps to some extent is, as you say, a pretty low bar to reach. Does that include also the question of whether it could potentially do any harm? Yeah, I think that it has a lot of data. Actually, it's been used by seventy thousand people at this point, and there's a lot of safety data at that point. That's a lot of people to use it. And there's known problems with when people receive transfusions of blood or plasma that there are known side effects and they're pretty typical I think for what people know about plasma. So I think one of the reasons why both hydroxy chloroquin and convalescent plasma meth this bar for the emergency use authorization was in part because the data on side effects is pretty well known at least they've been used in other settings, and so there's not a lot of concern about safety other than the known side effects of plasma. Actually, well, that's the good news. But you also just mentioned in the same sentence as hydroxychloroquin which turned out on closer examination of the data not to have positive therapeutic effects. What is the aspect of the data that makes you think that that is not true of kindless and plasma therapy, that in fact there are reasons in the data. Is it that small and RCT randomized control trial or is it more to do with the observational data on the seventy thousand people who have been treated this way. Yeah, you know, it's sometimes I sit back and this is not the way to judge science. But I'd say, based on what I've seen, if I are a family member had COVID, what I want them to receive plasma and the answer is yes, So I must have some sense that it works. But it is partly from the small randomized trial. It is partly from what you see in the data, which, although there's no control group, which is the huge problem, there are some signs that it would work. You cannot know for sure. Until you do the randomized trial. That's why this is an authorization and not approval, and there's a clear distinction between approval and all zation. And to authorize it in the setting of a public health emergency with no other treatment, you just have to think that it's probably going to work and have enough evidence that someone at FDA is going to say that it probably works. That's a hugely important point that you're making. There will lead and I just want to pause and emphasize it. Emergency use authorization is its own category, and it's different from FDA approval. FDA approval has higher standards for whether a treatment is approved, and that includes real statistical presumably RCT randomized control trial proof that it actually is working, whereas emergency use authorization simply consists of the statement that there's more reason to believe than not that it's helping. Is that a fair distinction between the two. Yes, that there's a reason to believe that the benefits outweigh the risks and approval full approval. Regular FDA approval typically requires a randomized trial. So yeah, that is a key issue with emergency use authorizations. The bar is lower. It's very different than FDA approval. And the other thing that's really interesting about emergency use authorizations is one of the criterias that there is no other approof therapy to treat the disease. And what's interesting is that it's approved therapy. So even though remdezeviere is the anti viral that is authorized also under the emergency use authorization, there is still no approved therapy. So as long as nothing is approved, they can actually still authorize what they need to because there is no approved therapy. While we're on the topic of emergency use authorization, let me ask you a question that I've been asked repeatedly by other lay people, and I have declined to answer because I don't know. But I bet you do know. When the time comes to try out for the public some of the vaccines that are being tested right now for SARS CoV two, is it conceivable that the FDA would do emergency use authorizations for the vaccines rather than issue full approvals because that would lower the standard of proof that needed to be met and would also presumably speed up the process. Yes, the answer is yes. And this is what I tell people is the most people could care less about convalescent plasma. Most people will never get it because it's given to hospitalize patients. The reason why it matters so much is because of exactly what you mentioned, which is everybody is really concerned about what this means for the vaccine. The answer is yes, that a vaccine can and in my view and others, likely will be authorized by the FDA through the same mechanism soon actually in terms of months. And there's a lot of debate about then, well good, because that's where we're headed. In order to get there, I think we first need to turn to the very troubling way, at least to my mind, that the announcement about the convalescent plasma therapy was made in a dramatic President of the United States participating press conference with statistics cited that, as far as I can make out, we're just not substantiated, namely that the treatment had reduced deaths by thirty five percent, which is something that the President said, the Secretary of HHS said, and then perhaps most disturbingly, the Commissioner of the FDA said, talk to us about what happened there? Where did this thirty five percent number come from? If you have a theory about where and why was it wrong, if indeed you believe it was wrong. Yeah, this is one of the most astounding things that happened. And I've tried to make a very clear distinction personally between whether I agree with an emergency use authorization and whether I agree with how it was delivered or how it was announced, which I do not. So that latter part that was just unprecedented, where you had such huge errors made in how the FDA talks about data for products that is authorized. Doesn't do those mistakes. If you read the decisional memo that the FDA puts together when they actually write, the FDA staff right, all the reasons why it should be authorized, all the data they make their decision, it's actually very detailed, very nuanced. But that is not what we heard at the press conference. That is also why people are so attuned to this issue of convalescent plasma, because we need the FDA to be telling us what is correct and saying it correctly and not misinforming the public, which is what they did here. So it's important to talk about that. So a couple of things, this thirty five out of one hundred issue the data supporting an emergency use authorization, for convalescent plasma did not come from a randomized trial, So it is very difficult to make conclusions about whether any therapy actually reduce mortality because there was no control arm. There was no arm that got nothing. So you really shouldn't say that there's good evidence that anything reduces mortality. What is there in terms of data? There are data that shows if you look at a subgroup subgroup of individuals, and you compare those who got more antibodies in their plasma with those who got fewer antibodies, there is a reduction in mortality. That the people who had more antibodies in their plasma, which conceivably should have more of an effect in reducing the severity disease, they actually had less mortality than the people that had lower tighters of anybody. And that the people who got the therapy earlier, when theoretically it should work better, had lower mortality than those who got it later. Still, we cannot be certain. You cannot go in front of the American public and say that this therapy reduces mortality when there's that possibility that it might not, and the audience that's listening does not understand all these nuances we've talking about about the bar emergency use authorization, randomized trials necessarily, So that is a key issue. Here's a question if the head of the FDA or the head of HHAs or the President for that matter, had not said this reduces mortality, but had said, we have reason to think that it might reduce mortality. Would that have made you less upset without it satisfied you. Is this a question of the clarity of the claim. Yes. So that's the thing is that the FDA had no reason to try and inflate the claim. The data as they stand are enough to say we're going to authorize it. We believe that in the case of an emergency people are dying. We want to get this to you. All of that is reasonable. That the problem was is going and saying that it reduces mortality when we don't know that. You know, even the bigger problem was saying that thirty five out of one hundred people will survive if they get the therapy. That is just nowhere near correct. That just flat out false. As far as I can make out, it's false. So not only was the certainty about the mortality benefit misstated, but the actual magnitude of that was misstated. We'll be right back. Let's turn now from what happened in this rollout to its implications for the really massive question of what's going to happen for vaccines. What consequences do you think this to a certain degree botched emergency use authorization rollout for the convalescent plasma has for the question of how much the public can, should, or will trust a potential emergency use authorization for vaccines. Yeah, one of the real problems we've had in the public health approach or has been the politicization of the entire thing. The problem with what happened here is that it just gave an opening of even more politicization, even more criticizing, so that it was the same thing with hydroxy clark, when there was huge criticism of the FDA from one side, huge applauding from the other side, and you have these two sides that are just completely different saying completely different things, you know, one saying it's the best thing ever, one saying it's the worst thing ever. And what happened here was just yet another opportunity for that to happen. Instead of having a message that is clear, that is correct, that is not overhyping things. It just contributed to the hype on one side about the benefit and so then the other side started a pile on the FDA. So that's part of the problem is that it's just adding to the politicization of public health. So what happens is it just leads to further distrust and you don't know who to trust, and so I think people end up just going to listen to who they trust, which is a problem. So all of this is leading up to this issue about what's going to happen when the FDA announces, When there's a press conference at the end of October and the president announces and the head of the FDA, they head the CDC is there and they announced that they have authorized a vaccine and they say that the vaccine is safe and effective. Ideally, we'd want the public to say, the President, the head of the CDC, the head of the FDA are telling us a vaccine is safe and effective. Great, we can all celebrate. The problem is is that that's not what's going to happen, and that's going to make this issue of vaccine so dicey. How our scientists going to respond about the vaccine when there's going to be nuanced date on safety and efficacy. What we don't want is scientists going out and saying this vaccine is not safe when they want people to take other vaccines, and the public will not get the nuance. That's the larger issue for me is this issue about polarization of science and public health, distrust, mistrust, confusion, and what that means for the vaccine, which is really the way that we're going to finish with this whole COVID thing and be able to get back to normal. You've kind of blown my mind in what you just said. So I want to walk through your scenario, which let's call the October surprise, which to you is not going to be such a surprise. You pick the end of October, I presume not solely because you think that by then will have enough preliminary data to make some kind of an initial judgment about the vaccines, but rather because it's approximate to the beginning of November and then the president wants to be reelected. So if I'm right about that, what you're picturing is a nationally televised press conference. The President's going to get up there and sort of like do his version of Barack Obama. You know, ladies and gentleman, we got him. He's going to go up there and he's going to say, in your scenario, ladies and gentlemen, we cured it. All problems solved. So, first of all, is that indeed something like the October surprise scenario that you're describing. Let me make sure I'm hearing you correctly. That is like the October surprise that I'm talking about. But the reason why I say late October is because there is already a meeting schedule of the FDA Advisory Committee that advises the FDA on vaccines, and the specific topic is the authorization of COVID vaccines. Now they have said specifically, the FDA Commissioner has said specifically that no specific application is going to be discussed, So it's as of now, there is no plan to discuss a specific vaccine that's going to be authorized. From what they said now, the FDA has said multiple settings of written and verbal that they will have an advisory committee meeting to review the safety and efficacy of a vaccine before anything is authorized. So they've made that commitment. So those pieces of data are they've said there's going to be advisory committee meeting before they authorize a vaccine. There is a vaccine Advisory Committee meeting scheduled for October twenty second. They're going to discuss the COVID vaccine in general. So that's one part of the puzzle. The other part of the puzzle is there's little snippets of what you call them rumor or news come out about the idea of using data from trials overseas to authorize a therapy if the trials here are not finished. There's a vaccine out of the University of Oxford that is doing trials outside of the US but hasn't really advanced trials inside the US, and there's some talk about that one of the trial sites was stopped because the FDA is saying, maybe we can use data from overseas. The other issue is that we've heard more and more just this opening about we would consider an emergency use authorization for the vaccine. So we keep hearing that, and that we keep hearing that there is a push politically to have a vaccine before the election. So whether it happens or not, no one knows, but everything is aligned in terms of a low bar for an authorization a Vaccine Advisory Committee meeting, trials that are quite advanced, and I could argue one could make the argument that it could fit the bar for an emerge use authorization. The stage is set that this could actually happen politically. Now if I can put my unofficial pundit head, and I'm not a pundit, but for the President to go up and announce that there's a vaccine does not require that it's a vaccine that everyone has access to or will take. So what some people have talked about is an emergency use authorization that is first very specific, tailored population, a small group of individuals, that allows the administration to say, look, we got a vaccine, but without having to deal with all the issues of well is it really safe? Is the entire public going to get it? It will just be authorized for a small population. Those are many reasons to think that it's at least possible that after the October twenty two Vaccine Committee FDA meeting, if the agenda is tweaked a little bit in the run up to that meeting such that's specific and concrete vaccines or discussed rather than the issue in the abstract, that there could be as a result potentially of White House pressure. But maybe, I mean, let's not be totally cynical. Maybe as a result of early findings from around the world that seemed plausible that there could be some kind of an announcement of an emergency use authorization with enough time before the election for that to affect people's minds. What do you see as the potential upsides or downsides of an announcement like that, Right, the whole point is we're in an emergency and a thousand people that they are dying. If there is something that can stop that, that is good. So the upside if there is really good data from overseas and it just doesn't fulfill the requirements of a full approval in the FDA here, well, I mean most people would agree that that should be authorized. That would require a full Phase three trial that's completed, where you give it to enough people and you have enough cases to say that there really is a reduction in the evalence of COVID or the severity of COVID. If you give people a vaccine and the FDA has made specific guidelines on how much of an effect they want, they want at least a fifty percent effect. Fifty percent fewer cases among those who are vaccinated versus non vaccinated. So that's a clear upside. If there's a vaccine that works, we feel good that it works. Well, then let's get it available so people don't have to wait for all the red tape to happen. Then I guess it's a spectrum of things. So go down the spectrum a little bit, and well, the Phase three trials are not completed, but they're almost completed. There maybe is an effect, but there's not enough cases to know for sure, but there's no real safety issues. I can easily see an argument there being made that, well, we have data so far in the data, we don't have any big safety issues. We have the early trials, and we have the Phase three trials saying yeah, there may be an effect. It may not reach statistical significance because there's not enough people, but it's it's almost there, and then it goes all the way down. How far you want to think about what the administration could say that would still fit the criteria for an emergency use austhorization? Is it reasonable to say that the probability of a benefit outweighs the probability of a risk with some lesser kind of data, and it's possible. And it depends on which vaccine they're talking about, because some of them are new vaccines that have never been used before. Some of them are just variants of another vaccine. So the downsides are One is side effects. You do not want a vaccine to be authorized people excited and then all of a sudden people die or become paralyzed when they start taking a vaccine. That would be a disaster. The other issue is, let's say there's a vaccine where the preliminary data is positive, but it ends up being just a little effective. It maybe reduces the chance of having COVID by twenty percent, but there's still trials ongoing to test the vaccine that might be better. The problem is you're going to have people who want to get back to their lives and they're going to have a vaccine on the market, and the question is are they going to take that vaccine and then not enroll in other trials that might get us a better vaccine, and then we'll never know. We'll never get to that better vaccine. That's one concern is that the randomized trials will not fully enroll and we end up authorizing a vaccine that's okay, and not really getting those vaccines to market that are really, really good and maybe a little safer. What about the risk that politicization just engulfs the announcement. I think the thing that's most striking to me is, you know, we spent the first part of our conversation talking about just how bad it was that there's this politicization surrounding I think your phrase was, I jotted it down, the politicization of the entire thing, the entire thing being, you know, the whole question of treatment of COVID. If the President announces an EUA for a vaccine in late October, I know how you avoid radical politicization, and I don't know how you avoid Democrats, maybe not Joe Biden, but certainly other Democrats saying it's too soon, this isn't safe, you shouldn't do it. And then that really could create a circumstance where many many people, like roughly half the people, have some deep skepticism about the vaccine. Can you imagine this scenarrea where the Democrats were at least some Democrats would go down that road. Yes, yes, And that's the problem. I've already seen it in politicization of other issues in public health. And it's not only what they say, it's how they say it and in what context they say it. A lot of the decisions that Democrats and those that lean Democrat have disagreed with, the criticism has been couched in the language that is about how the president is terrible, etc. Etc. So the problem is is that will definitely happen with the vaccine, and it will be things like no one should take this vaccine, no one should trust Trump, the data are terrible. Trump has let us astray. The problem is where is the nuance? Where is the truth going to come from? And that's what I meant before about the problem with thirty five out of one hundred thing from the head of the FDA about plasma. Where is the truth going to come from? I mean, what you're just described sounds great from the standpoint of Trump, especially if he's pulling closer in the polls but is still down. And now you know, imagine if you will, being inside Joe Biden's strategy session as Donald Trump is calling this press conference and holding it, his advisors are going to be telling him, well, mister Biden, if you don't challenge this, it may hurt you in the vote in the next week. But if you do challenge it, if you do say it's too soon, and then you're elected, then by the time whatever vaccine the president is talking about is actually available, because the vaccines themselves doesn't seem plausible, would be available at the end of October. It would just be the announcement that was happening then at the time the vaccines were actually being produced in sufficient quantities and distributed with sufficient efficiency to reach Americans. Joe Biden could be president and then he would be in a disastrous position if he had first said that we shouldn't take the vaccine, and then he were president and he wanted to hand out the vaccine. So you can imagine that strategy session being frankly, a bit of a nightmare. Two. So what you're describing is making me. With everything you say, I'm getting more and more concerned that this could actually happen. Yeah, and I am not a political pundit, but I, like many people, think a lot about these things. But I have the same concern, and I think, what will happen in October? If there is an announcement like this, it will inevitably be politicized, and the vaccine is our way out, and we just don't want to mess this up. We have messed up so much in the response to this pandemic. The vaccine is the way out. We do not want to mess that up. But yet to be able to be the president and stand up a week or two before you're election and say we from day one put in billions of dollars and warp speed. Look what we've done. We've authorized the vaccine for a small group that that obviously will bring a lot of benefits. Thank you a lead for genuinely powerful analysis, and thank you for your clarity and your even handedness around these really challenging questions. I hope he'll come back and talk more with us if indeed there is an October surprise. It's a pleasure to talk to you. Yet, I'd be happy to come back, and hopefully the October surprise is a good one. Listening to doctor Jelat describe what went wrong in the rollout of convalescent plasma therapy was pretty eye opening. First of all, he pointed out that when it comes down to it, convalescent plasma therapy may actually be a good thing, he supported and said it was correct for the FDA to issue its emergency use authorization. At the same time, he didn't pull any punches in saying that it was astounding and unprecedented for the head of the FDA to make flatly false statements about the degree of efficacy of a treatment and then not fully back away subsequently from those claims. Yet, for all the importance of these events, what most stunned me in my conversation with Walid was his very close to a prediction, or at least his alerting us to the possibility that after the special October twenty second meeting of the FDA's Vaccines Committee, there could well be a presidential announcement of an emergency use authorization for a vaccine. Now, to be sure, we don't know whether that will happen, and while he did not say that he knew that it would. Instead, what we were doing was trying to pull together probabilistic evidence based on the incentives of the parties, based on what had been said and announced publicly, and based on what we think Trump like to do if he were able. It's important to note that Wali did not say that would necessarily be a bad thing for the President to issue this emergency use authorization. If indeed he did, that would all depend on what the data showed at the relevant time. We all want to get this vaccine to as many people as possible, even if in practice it seems extremely unlikely that vaccines would actually be available in October. Yet there is simultaneously a really significant risk that if a vaccine will rolled out too soon, it might crush public confidence in the FDA and eventually public confidence in the efficacy of a vaccine, and that too has potentially very serious public health effects. The upshot is that we should all be watching much more closely than I have been until this moment to figure out what the FDA is actually going to do at its committee's October twenty second meeting, And we should be watching the press residence moves very carefully to see whether the White House thinks it has something to gain from an emergency use authorization. Then at the same time, we'll all keep hoping that the data is good and that the vaccines work, and that it is possible to get them to people as soon as possible. I make no secret of my desire to see Donald Trump out of office, but It's in the end much more important to save lives. Until the next time I speak to you, be careful, be safe, and be well. Deep Background is brought to you by Pushkin Industries. Our producer is Lydia gene Cott, with mastering by Jason Gambrell and Martin Gonzalez. Our showrunner is Sophie mckibbon. Our theme music is composed by Luis GERA special thanks to the Pushkin Brass, Malcolm Gladwell, Jacob Weisberg, and Mia Lobel. I'm Noah Feldman. I also write a regular column for Bloomberg Opinion, which you can find at Bloomberg dot com slash Feldman. To discover bloom original slate of podcasts, go to Bloomberg dot com slash Podcasts. And one last thing. I just wrote a book called The Arab Winter, a Tragedy. I would be delighted if you checked it out. If you liked what you heard today, please write a review or tell a friend. You can always let me know what you think on Twitter. My handle is Noah R. Feldman. This is Deep Background.

Pushkin from Pushkin Industries. This is Deep Background the show where we explored the stories behind the stories in the news. I'm Noah Feldman. The Food and Drug Administration recently issued an emergency use authorization for doctors to take blood plasma from patients who have recovered from COVID nineteen and use it as a therapy for patients who are sick enough with the disease right now that they find themselves in the hospital. While announcing this authorization, the FDA Commissioner Stephen Hahn said that thirty five out of one hundred of COVID nineteen patients quote would have been saved because of the administration of plasma close quote. This led to an outcry from scientists pointing out that this statement vastly overstated the treatment benefits, criticism that Han later said was in fact justified. So what do we actually know about convalescent plasma as a treatment for COVID nineteen, And, perhaps more important, what does the mess of politicization around this emergency use authorization tell us about what might happen in the future if and when the Trump administration seeks to use an emergency use authorization to introduce a vaccine. Here to discuss these hugely important issues with US is doctor Walid Jelad. Doctor Gelatt is an assistant professor of medicine and health policy at the University of Pittsburgh, where he leads the Center for Pharmaceutical Policy and Prescribing. He has been a frequent and astute commentator on treatment statistics and reality. Well, thank you so much for being here. It's my pleasure. Today. We're going to start with convalescent plasma therapy. And although we're going to talk I think at some length about what is not true of convalescent plasmo therapy, Let's start with what is true of plasma therapy in your view, reading the data that has been made publicly available, what can plausibly be claimed for this therapy in terms of the effect that it could have on people who are ill with covid NT. There are different ways to think about this. I think so one. I think the claim can be made as it was made in the Emergency Use Authorization, which is why the EUA is interesting, And the claim is simply that the totality of the evidence says that it's probably going to help people, and I actually think it is fair to say then, and that's pretty much a low bar for what you need to determine if something is going to be authorized. But the FDA, but I think the totality of evidence, based on what we've seen in animals, in what was in a small randomized trial, and in some of these observational data that was seen from the Mayo clinic, is that it probably help helps to some extent. And that's really all you can say, probably helps to some extent is, as you say, a pretty low bar to reach. Does that include also the question of whether it could potentially do any harm? Yeah, I think that it has a lot of data. Actually, it's been used by seventy thousand people at this point, and there's a lot of safety data at that point. That's a lot of people to use it. And there's known problems with when people receive transfusions of blood or plasma that there are known side effects and they're pretty typical I think for what people know about plasma. So I think one of the reasons why both hydroxy chloroquin and convalescent plasma meth this bar for the emergency use authorization was in part because the data on side effects is pretty well known at least they've been used in other settings, and so there's not a lot of concern about safety other than the known side effects of plasma. Actually, well, that's the good news. But you also just mentioned in the same sentence as hydroxychloroquin which turned out on closer examination of the data not to have positive therapeutic effects. What is the aspect of the data that makes you think that that is not true of kindless and plasma therapy, that in fact there are reasons in the data. Is it that small and RCT randomized control trial or is it more to do with the observational data on the seventy thousand people who have been treated this way. Yeah, you know, it's sometimes I sit back and this is not the way to judge science. But I'd say, based on what I've seen, if I are a family member had COVID, what I want them to receive plasma and the answer is yes, So I must have some sense that it works. But it is partly from the small randomized trial. It is partly from what you see in the data, which, although there's no control group, which is the huge problem, there are some signs that it would work. You cannot know for sure. Until you do the randomized trial. That's why this is an authorization and not approval, and there's a clear distinction between approval and all zation. And to authorize it in the setting of a public health emergency with no other treatment, you just have to think that it's probably going to work and have enough evidence that someone at FDA is going to say that it probably works. That's a hugely important point that you're making. There will lead and I just want to pause and emphasize it. Emergency use authorization is its own category, and it's different from FDA approval. FDA approval has higher standards for whether a treatment is approved, and that includes real statistical presumably RCT randomized control trial proof that it actually is working, whereas emergency use authorization simply consists of the statement that there's more reason to believe than not that it's helping. Is that a fair distinction between the two. Yes, that there's a reason to believe that the benefits outweigh the risks and approval full approval. Regular FDA approval typically requires a randomized trial. So yeah, that is a key issue with emergency use authorizations. The bar is lower. It's very different than FDA approval. And the other thing that's really interesting about emergency use authorizations is one of the criterias that there is no other approof therapy to treat the disease. And what's interesting is that it's approved therapy. So even though remdezeviere is the anti viral that is authorized also under the emergency use authorization, there is still no approved therapy. So as long as nothing is approved, they can actually still authorize what they need to because there is no approved therapy. While we're on the topic of emergency use authorization, let me ask you a question that I've been asked repeatedly by other lay people, and I have declined to answer because I don't know. But I bet you do know. When the time comes to try out for the public some of the vaccines that are being tested right now for SARS CoV two, is it conceivable that the FDA would do emergency use authorizations for the vaccines rather than issue full approvals because that would lower the standard of proof that needed to be met and would also presumably speed up the process. Yes, the answer is yes. And this is what I tell people is the most people could care less about convalescent plasma. Most people will never get it because it's given to hospitalize patients. The reason why it matters so much is because of exactly what you mentioned, which is everybody is really concerned about what this means for the vaccine. The answer is yes, that a vaccine can and in my view and others, likely will be authorized by the FDA through the same mechanism soon actually in terms of months. And there's a lot of debate about then, well good, because that's where we're headed. In order to get there, I think we first need to turn to the very troubling way, at least to my mind, that the announcement about the convalescent plasma therapy was made in a dramatic President of the United States participating press conference with statistics cited that, as far as I can make out, we're just not substantiated, namely that the treatment had reduced deaths by thirty five percent, which is something that the President said, the Secretary of HHS said, and then perhaps most disturbingly, the Commissioner of the FDA said, talk to us about what happened there? Where did this thirty five percent number come from? If you have a theory about where and why was it wrong, if indeed you believe it was wrong. Yeah, this is one of the most astounding things that happened. And I've tried to make a very clear distinction personally between whether I agree with an emergency use authorization and whether I agree with how it was delivered or how it was announced, which I do not. So that latter part that was just unprecedented, where you had such huge errors made in how the FDA talks about data for products that is authorized. Doesn't do those mistakes. If you read the decisional memo that the FDA puts together when they actually write, the FDA staff right, all the reasons why it should be authorized, all the data they make their decision, it's actually very detailed, very nuanced. But that is not what we heard at the press conference. That is also why people are so attuned to this issue of convalescent plasma, because we need the FDA to be telling us what is correct and saying it correctly and not misinforming the public, which is what they did here. So it's important to talk about that. So a couple of things, this thirty five out of one hundred issue the data supporting an emergency use authorization, for convalescent plasma did not come from a randomized trial, So it is very difficult to make conclusions about whether any therapy actually reduce mortality because there was no control arm. There was no arm that got nothing. So you really shouldn't say that there's good evidence that anything reduces mortality. What is there in terms of data? There are data that shows if you look at a subgroup subgroup of individuals, and you compare those who got more antibodies in their plasma with those who got fewer antibodies, there is a reduction in mortality. That the people who had more antibodies in their plasma, which conceivably should have more of an effect in reducing the severity disease, they actually had less mortality than the people that had lower tighters of anybody. And that the people who got the therapy earlier, when theoretically it should work better, had lower mortality than those who got it later. Still, we cannot be certain. You cannot go in front of the American public and say that this therapy reduces mortality when there's that possibility that it might not, and the audience that's listening does not understand all these nuances we've talking about about the bar emergency use authorization, randomized trials necessarily, So that is a key issue. Here's a question if the head of the FDA or the head of HHAs or the President for that matter, had not said this reduces mortality, but had said, we have reason to think that it might reduce mortality. Would that have made you less upset without it satisfied you. Is this a question of the clarity of the claim. Yes. So that's the thing is that the FDA had no reason to try and inflate the claim. The data as they stand are enough to say we're going to authorize it. We believe that in the case of an emergency people are dying. We want to get this to you. All of that is reasonable. That the problem was is going and saying that it reduces mortality when we don't know that. You know, even the bigger problem was saying that thirty five out of one hundred people will survive if they get the therapy. That is just nowhere near correct. That just flat out false. As far as I can make out, it's false. So not only was the certainty about the mortality benefit misstated, but the actual magnitude of that was misstated. We'll be right back. Let's turn now from what happened in this rollout to its implications for the really massive question of what's going to happen for vaccines. What consequences do you think this to a certain degree botched emergency use authorization rollout for the convalescent plasma has for the question of how much the public can, should, or will trust a potential emergency use authorization for vaccines. Yeah, one of the real problems we've had in the public health approach or has been the politicization of the entire thing. The problem with what happened here is that it just gave an opening of even more politicization, even more criticizing, so that it was the same thing with hydroxy clark, when there was huge criticism of the FDA from one side, huge applauding from the other side, and you have these two sides that are just completely different saying completely different things, you know, one saying it's the best thing ever, one saying it's the worst thing ever. And what happened here was just yet another opportunity for that to happen. Instead of having a message that is clear, that is correct, that is not overhyping things. It just contributed to the hype on one side about the benefit and so then the other side started a pile on the FDA. So that's part of the problem is that it's just adding to the politicization of public health. So what happens is it just leads to further distrust and you don't know who to trust, and so I think people end up just going to listen to who they trust, which is a problem. So all of this is leading up to this issue about what's going to happen when the FDA announces, When there's a press conference at the end of October and the president announces and the head of the FDA, they head the CDC is there and they announced that they have authorized a vaccine and they say that the vaccine is safe and effective. Ideally, we'd want the public to say, the President, the head of the CDC, the head of the FDA are telling us a vaccine is safe and effective. Great, we can all celebrate. The problem is is that that's not what's going to happen, and that's going to make this issue of vaccine so dicey. How our scientists going to respond about the vaccine when there's going to be nuanced date on safety and efficacy. What we don't want is scientists going out and saying this vaccine is not safe when they want people to take other vaccines, and the public will not get the nuance. That's the larger issue for me is this issue about polarization of science and public health, distrust, mistrust, confusion, and what that means for the vaccine, which is really the way that we're going to finish with this whole COVID thing and be able to get back to normal. You've kind of blown my mind in what you just said. So I want to walk through your scenario, which let's call the October surprise, which to you is not going to be such a surprise. You pick the end of October, I presume not solely because you think that by then will have enough preliminary data to make some kind of an initial judgment about the vaccines, but rather because it's approximate to the beginning of November and then the president wants to be reelected. So if I'm right about that, what you're picturing is a nationally televised press conference. The President's going to get up there and sort of like do his version of Barack Obama. You know, ladies and gentleman, we got him. He's going to go up there and he's going to say, in your scenario, ladies and gentlemen, we cured it. All problems solved. So, first of all, is that indeed something like the October surprise scenario that you're describing. Let me make sure I'm hearing you correctly. That is like the October surprise that I'm talking about. But the reason why I say late October is because there is already a meeting schedule of the FDA Advisory Committee that advises the FDA on vaccines, and the specific topic is the authorization of COVID vaccines. Now they have said specifically, the FDA Commissioner has said specifically that no specific application is going to be discussed, So it's as of now, there is no plan to discuss a specific vaccine that's going to be authorized. From what they said now, the FDA has said multiple settings of written and verbal that they will have an advisory committee meeting to review the safety and efficacy of a vaccine before anything is authorized. So they've made that commitment. So those pieces of data are they've said there's going to be advisory committee meeting before they authorize a vaccine. There is a vaccine Advisory Committee meeting scheduled for October twenty second. They're going to discuss the COVID vaccine in general. So that's one part of the puzzle. The other part of the puzzle is there's little snippets of what you call them rumor or news come out about the idea of using data from trials overseas to authorize a therapy if the trials here are not finished. There's a vaccine out of the University of Oxford that is doing trials outside of the US but hasn't really advanced trials inside the US, and there's some talk about that one of the trial sites was stopped because the FDA is saying, maybe we can use data from overseas. The other issue is that we've heard more and more just this opening about we would consider an emergency use authorization for the vaccine. So we keep hearing that, and that we keep hearing that there is a push politically to have a vaccine before the election. So whether it happens or not, no one knows, but everything is aligned in terms of a low bar for an authorization a Vaccine Advisory Committee meeting, trials that are quite advanced, and I could argue one could make the argument that it could fit the bar for an emerge use authorization. The stage is set that this could actually happen politically. Now if I can put my unofficial pundit head, and I'm not a pundit, but for the President to go up and announce that there's a vaccine does not require that it's a vaccine that everyone has access to or will take. So what some people have talked about is an emergency use authorization that is first very specific, tailored population, a small group of individuals, that allows the administration to say, look, we got a vaccine, but without having to deal with all the issues of well is it really safe? Is the entire public going to get it? It will just be authorized for a small population. Those are many reasons to think that it's at least possible that after the October twenty two Vaccine Committee FDA meeting, if the agenda is tweaked a little bit in the run up to that meeting such that's specific and concrete vaccines or discussed rather than the issue in the abstract, that there could be as a result potentially of White House pressure. But maybe, I mean, let's not be totally cynical. Maybe as a result of early findings from around the world that seemed plausible that there could be some kind of an announcement of an emergency use authorization with enough time before the election for that to affect people's minds. What do you see as the potential upsides or downsides of an announcement like that, Right, the whole point is we're in an emergency and a thousand people that they are dying. If there is something that can stop that, that is good. So the upside if there is really good data from overseas and it just doesn't fulfill the requirements of a full approval in the FDA here, well, I mean most people would agree that that should be authorized. That would require a full Phase three trial that's completed, where you give it to enough people and you have enough cases to say that there really is a reduction in the evalence of COVID or the severity of COVID. If you give people a vaccine and the FDA has made specific guidelines on how much of an effect they want, they want at least a fifty percent effect. Fifty percent fewer cases among those who are vaccinated versus non vaccinated. So that's a clear upside. If there's a vaccine that works, we feel good that it works. Well, then let's get it available so people don't have to wait for all the red tape to happen. Then I guess it's a spectrum of things. So go down the spectrum a little bit, and well, the Phase three trials are not completed, but they're almost completed. There maybe is an effect, but there's not enough cases to know for sure, but there's no real safety issues. I can easily see an argument there being made that, well, we have data so far in the data, we don't have any big safety issues. We have the early trials, and we have the Phase three trials saying yeah, there may be an effect. It may not reach statistical significance because there's not enough people, but it's it's almost there, and then it goes all the way down. How far you want to think about what the administration could say that would still fit the criteria for an emergency use austhorization? Is it reasonable to say that the probability of a benefit outweighs the probability of a risk with some lesser kind of data, and it's possible. And it depends on which vaccine they're talking about, because some of them are new vaccines that have never been used before. Some of them are just variants of another vaccine. So the downsides are One is side effects. You do not want a vaccine to be authorized people excited and then all of a sudden people die or become paralyzed when they start taking a vaccine. That would be a disaster. The other issue is, let's say there's a vaccine where the preliminary data is positive, but it ends up being just a little effective. It maybe reduces the chance of having COVID by twenty percent, but there's still trials ongoing to test the vaccine that might be better. The problem is you're going to have people who want to get back to their lives and they're going to have a vaccine on the market, and the question is are they going to take that vaccine and then not enroll in other trials that might get us a better vaccine, and then we'll never know. We'll never get to that better vaccine. That's one concern is that the randomized trials will not fully enroll and we end up authorizing a vaccine that's okay, and not really getting those vaccines to market that are really, really good and maybe a little safer. What about the risk that politicization just engulfs the announcement. I think the thing that's most striking to me is, you know, we spent the first part of our conversation talking about just how bad it was that there's this politicization surrounding I think your phrase was, I jotted it down, the politicization of the entire thing, the entire thing being, you know, the whole question of treatment of COVID. If the President announces an EUA for a vaccine in late October, I know how you avoid radical politicization, and I don't know how you avoid Democrats, maybe not Joe Biden, but certainly other Democrats saying it's too soon, this isn't safe, you shouldn't do it. And then that really could create a circumstance where many many people, like roughly half the people, have some deep skepticism about the vaccine. Can you imagine this scenarrea where the Democrats were at least some Democrats would go down that road. Yes, yes, And that's the problem. I've already seen it in politicization of other issues in public health. And it's not only what they say, it's how they say it and in what context they say it. A lot of the decisions that Democrats and those that lean Democrat have disagreed with, the criticism has been couched in the language that is about how the president is terrible, etc. Etc. So the problem is is that will definitely happen with the vaccine, and it will be things like no one should take this vaccine, no one should trust Trump, the data are terrible. Trump has let us astray. The problem is where is the nuance? Where is the truth going to come from? And that's what I meant before about the problem with thirty five out of one hundred thing from the head of the FDA about plasma. Where is the truth going to come from? I mean, what you're just described sounds great from the standpoint of Trump, especially if he's pulling closer in the polls but is still down. And now you know, imagine if you will, being inside Joe Biden's strategy session as Donald Trump is calling this press conference and holding it, his advisors are going to be telling him, well, mister Biden, if you don't challenge this, it may hurt you in the vote in the next week. But if you do challenge it, if you do say it's too soon, and then you're elected, then by the time whatever vaccine the president is talking about is actually available, because the vaccines themselves doesn't seem plausible, would be available at the end of October. It would just be the announcement that was happening then at the time the vaccines were actually being produced in sufficient quantities and distributed with sufficient efficiency to reach Americans. Joe Biden could be president and then he would be in a disastrous position if he had first said that we shouldn't take the vaccine, and then he were president and he wanted to hand out the vaccine. So you can imagine that strategy session being frankly, a bit of a nightmare. Two. So what you're describing is making me. With everything you say, I'm getting more and more concerned that this could actually happen. Yeah, and I am not a political pundit, but I, like many people, think a lot about these things. But I have the same concern, and I think, what will happen in October? If there is an announcement like this, it will inevitably be politicized, and the vaccine is our way out, and we just don't want to mess this up. We have messed up so much in the response to this pandemic. The vaccine is the way out. We do not want to mess that up. But yet to be able to be the president and stand up a week or two before you're election and say we from day one put in billions of dollars and warp speed. Look what we've done. We've authorized the vaccine for a small group that that obviously will bring a lot of benefits. Thank you a lead for genuinely powerful analysis, and thank you for your clarity and your even handedness around these really challenging questions. I hope he'll come back and talk more with us if indeed there is an October surprise. It's a pleasure to talk to you. Yet, I'd be happy to come back, and hopefully the October surprise is a good one. Listening to doctor Jelat describe what went wrong in the rollout of convalescent plasma therapy was pretty eye opening. First of all, he pointed out that when it comes down to it, convalescent plasma therapy may actually be a good thing, he supported and said it was correct for the FDA to issue its emergency use authorization. At the same time, he didn't pull any punches in saying that it was astounding and unprecedented for the head of the FDA to make flatly false statements about the degree of efficacy of a treatment and then not fully back away subsequently from those claims. Yet, for all the importance of these events, what most stunned me in my conversation with Walid was his very close to a prediction, or at least his alerting us to the possibility that after the special October twenty second meeting of the FDA's Vaccines Committee, there could well be a presidential announcement of an emergency use authorization for a vaccine. Now, to be sure, we don't know whether that will happen, and while he did not say that he knew that it would. Instead, what we were doing was trying to pull together probabilistic evidence based on the incentives of the parties, based on what had been said and announced publicly, and based on what we think Trump like to do if he were able. It's important to note that Wali did not say that would necessarily be a bad thing for the President to issue this emergency use authorization. If indeed he did, that would all depend on what the data showed at the relevant time. We all want to get this vaccine to as many people as possible, even if in practice it seems extremely unlikely that vaccines would actually be available in October. Yet there is simultaneously a really significant risk that if a vaccine will rolled out too soon, it might crush public confidence in the FDA and eventually public confidence in the efficacy of a vaccine, and that too has potentially very serious public health effects. The upshot is that we should all be watching much more closely than I have been until this moment to figure out what the FDA is actually going to do at its committee's October twenty second meeting, And we should be watching the press residence moves very carefully to see whether the White House thinks it has something to gain from an emergency use authorization. Then at the same time, we'll all keep hoping that the data is good and that the vaccines work, and that it is possible to get them to people as soon as possible. I make no secret of my desire to see Donald Trump out of office, but It's in the end much more important to save lives. Until the next time I speak to you, be careful, be safe, and be well. Deep Background is brought to you by Pushkin Industries. Our producer is Lydia gene Cott, with mastering by Jason Gambrell and Martin Gonzalez. Our showrunner is Sophie mckibbon. Our theme music is composed by Luis GERA special thanks to the Pushkin Brass, Malcolm Gladwell, Jacob Weisberg, and Mia Lobel. I'm Noah Feldman. I also write a regular column for Bloomberg Opinion, which you can find at Bloomberg dot com slash Feldman. To discover bloom original slate of podcasts, go to Bloomberg dot com slash Podcasts. And one last thing. I just wrote a book called The Arab Winter, a Tragedy. I would be delighted if you checked it out. If you liked what you heard today, please write a review or tell a friend. You can always let me know what you think on Twitter. My handle is Noah R. Feldman. 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