A Breakdown on Preprints With Eric Topol, MD

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JOHN WHYTE: Welcome, everyone. I'm Dr. John Whyte, the chief medical officer at WebMD, and you're watching Coronavirus in Context. One of the things that we've seen throughout the pandemic is this rapidly emerging science. And the traditional model is, let's wait until things get published, and then we'll talk more broadly about it. But we don't have the time to do that during literally a pandemic that impacts the world. So what's the role of preprints? Joining me to help explain the pros and cons is my good friend, the editor-in-chief of Medscape, Dr. Eric Topol. Eric, it's great to see you as always.

ERIC TOPOL: Great to be with you, John.

JOHN WHYTE: One thing we've talked about is a success story of the COVID pandemic has been the speed of innovation. And part of innovation in terms of pharmaceuticals, in terms of diagnostic tests is the ability to peer review, to have an outside group of experts look at it and assess it for its validity or its objectivity.

The pandemic, as I referenced in my remarks, hasn't allowed that. So we never really talked about preprints years ago. And now, if you remember early on in the pandemic, everyone was talking about it. So what's the role of preprint? And maybe we take a step back and help us define, what do we mean by that?

ERIC TOPOL: Right. Well, this is really important stuff to get into, John. And I spend a fair amount of my day now every day looking at preprints. The real story here is that they've been going for about 10 years in one platform or another. The one that is mostly affecting us is bio archives and med archives, which is handled by Cold Spring Press, Cold Spring Harbor.

And they are basically manuscripts that are put on that server after they've been screened. So they're not detailed peer-reviewed. But for example, they check if they have had IRB approval, and they basically fulfill good conduct of research, especially when it's clinical, but also lab-based research. And they have not yet gone out to peer review by journals. Although right now, many journals want people who are authors to put it on the preprint server first, because it's basically like the peer review. Because immediately after a good one's posted, Twitter is all over it.

So in a way, it's a whole different form of peer review, and it's really amazing. Like just yesterday I have to say, I kind of got blown away. Here Omicron, as you know, was just reported Thanksgiving, November, end of November. And a paper from Israel was reported with follow up through January 27 on a fourth dose on February 1, OK? So on millions of people, all right? So we would never see that data normally if it only went through peer review. It could take months. Months or maybe--

JOHN WHYTE: The argument could be, why don't we speed up peer review? Why don't we make it quicker and easier instead of saying preprint? And I have to ask you, is preprint the right term? Because for those that aren't involved in research like you, preprint, I'm going to be honest, sounds to some people, it's going to be published, right? And this is an early look. That's not the case.

ERIC TOPOL: Well, that's true. There are many preprints that never see the light of day. Quite a few are published. In fact, many in leading journals. It really is depending on who's writing the preprint. If it's coming from reputable people, they don't want to put something out there on the web. I mean, their name is on the line, right? So if it's something that's flawed, it's going to get picked up by the masses. I mean, there's so many people that look at every preprint on these different servers.

So I think you have to be very careful about who are the authors, where is it coming from. But your point is essential, John because what you said, well, what about just getting peer review faster? The problem is, when we do peer review, it's two or three people who sometimes don't even really go through the paper carefully. And they take a long time.

Even with the pressure of the pandemic, trying to get it down to a week or two, by the time you get three reviewers in or two reviewers in, and they're late and you have to just keep, the editors have to keep pinging them, it's all done on a voluntary basis. So the real thing is, peer review as we know it is that really the gold or platinum standard? Especially since it takes quite a while. So what you're comparing with are two different ways to get-- you can get a rapid mass review by experts and non-experts through a post on a preprint server.

JOHN WHYTE: It's like rapid and PCR in a way. Antigen test versus PCR. But still, people could argue and say change the peer review process. Pay academicians or whoever to review it. Hire more people. Like this is serious research that we really need to determine. But what about the fact where there has been this attack on science throughout the pandemic, people don't like when recommendations change because our knowledge of the science is evolving. And I pointed out, you and I have talked throughout these 24 plus months. Early on, there were a couple preprints that were wrong in terms of--

ERIC TOPOL: There's many

JOHN WHYTE: --what they thought about treatment, what they thought about infectiousness, et cetera. And people were starting to make decisions on that. Because the media doesn't really make that distinction. That it's preprint.

ERIC TOPOL: You're spot on on that.

JOHN WHYTE: How do we use preprints in the broader community because if it's not accurate because it's early it's still a little earlier on, that's a challenge. But we also don't want to miss opportunities and it's something that we need to address in terms of public health. How do we put it all together while recognizing sometimes it doesn't meet the rigor that we need?

ERIC TOPOL: Right. So the treatment side of the pandemic has been one of the most important abuses and misguided aspects. So hydroxychloroquine was one of the early preprints from France that was completely off base, and it set off this hydroxychloroquine. There's been the same for convalescent plasma, which I reacted to when I attacked the FDA commissioner and the administration September of 2020.

Basically, the preprint has much more contamination than you'll see through high-quality, peer-reviewed journals, right? And you have to ferret out what is either a likely suspect for contamination, wrong, versus the really high-quality ones.

JOHN WHYTE: I mean, the body of literature is enormous. It keeps doubling it seems like every few months. How does someone keep up with it? Because we can say, all right, we have all these journals. And there's more and more journals evolving. We have increased frequency. Now we have preprint to the degree that we never had before. How do you realistically keep up with it. I mean, there's only so many hours in the day. One could be reading preprints all day. How do you balance that? How do you how do you utilize preprints?

ERIC TOPOL: Yeah. I mean, I basically try to stick with top journals that I know well. And then I go through the three main preprint servers, at least for the pandemic. And I can pretty well look at 10 preprints, let's say, of their titles and authors, and know I'm only going interest to zoom in on one because I know these people or I know their work is impeccable. It's the real deal kind of thing. And I won't waste time looking at ones that I think I don't know the people or the topic is not particularly germane or whatever. That's how I do it.

JOHN WHYTE: Most people don't have your expertise. So do we need to create some type of curation almost like a Dr. Eric Topol AI curator to put those things explicit?

ERIC TOPOL: I would love to see-- your idea is very good, John-- I would love to see a panel reviewer of each preprint as they come out, like consumer reports and just give it the yellow or the red circle stuff. But we don't have that, and who are we going to get to do that? So you're right, it would help because I think the average person who doesn't know the players, the institutions, the whole landscape.

Like yesterday, there was a really interesting preprint about five people from University of Maryland who died. And in their brain, in their cortex, they had the virus in the cells. And they also had an inflammation activation that looked like Alzheimer's. And I read this, and oh, man, these are really good people. One of the leading Coronavirus virologists was part of this to make this determination.

As you know, it's been very controversial whether the virus gets into brain cells or just induces inflammation. So I shared that because I know it was a good study, and it's of course, a concern. And I shared that it's controversial. And if this is the real deal, we don't know how frequently it happens. And there were people that were upset. There were a few people that said, oh, you shouldn't have shared that. Well, it's actually important. What are we supposed to do, suppress it?

JOHN WHYTE: And it's a pretty how should the media use it? Because often then, those caveats that you described aren't mentioned.

ERIC TOPOL: Right. Right.

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