The COVID-19 pandemic has prompted scientists to use adaptive research designs to evaluate potential treatments simultaneously and efficiently, increasing the likelihood that patients will receive treatments most likely to be effective for them. Lennie Derde, MD, of University Medical Center Utrecht in the Netherlands and JAMA Associate Editor Christopher W. Seymour, MD, MSc, of University of Pittsburgh Medical Center join JAMA's Q&A series to discuss the latest in critical care management of COVID-19 patients and emerging treatment strategies and therapies.
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>> Howard Bauchner: Hello and welcome to Conversations With Dr. Bauchner. Once again, it is Howard Bauchner, editor-in-chief of "JAMA." And I'm joined by two intensivists. The first is Chris Seymour. Chris is an Associate Professor of Critical Care Medicine and Emergency Medicine at University of Pittsburgh Medical Center in Pittsburgh. And Chris recently became our Associate Editor in Critical Care Medicine. And we bumped Derek Angus up to Senior Editor position. The second person who's joining us is Lennie Derde. Lennie is an intensivist and a clinical investigator at the University Medical Center in Utrecht. And she's also the Intensive Care Consultant and European Coordinating Investigator of the Remap-Cap trial. Lennie and Chris, thanks for joining me today.
>> Christopher Seymour: Morning.
>> Howard Bauchner: And for our listeners, I just want to emphasize, you're welcome to send in questions, but this conversation will really focus on intensive care and the management of patients with critical illness from COVID-19 and not vaccines. But, Lennie, I want to start with you. Utrecht is in the Netherlands. What's it been like in your country and the surrounding countries for the last couple weeks?
>> Lennie Derde: Thanks, Howard. And thank you very much for having me on your conversations. So Utrecht is a relatively big city in the middle of the Netherlands. So it's smaller than Amsterdam, but we consider it the smallest of the big cities of the Netherlands. And so we had what we call a first wave in March/April, and then it got a little bit quieter. But since October, we've seen a re-surge of patients. So if I look at our ICU in my university hospital, we usually have 24 ICU beds open. We'd like to have more, but we just don't have, especially the ICU nurses. In the first wave we scaled up to 80-bed ICU in three different locations, so that was quite the surge. And on top of that we worked out of our comfort space because we did not have the 1 to 1 nursing to patient ratio that he we normally have, we have 1 to 1.5 or 1 to 1. But we had a 1 to 3 nurse to patient ratio, the other way around I think. So since October, we've, we're still in a surge. We're still using extra beds. On average we've had about 40 beds open and still working in a 1 to 3 ratio. So although it does feel a lot more quiet now, we're still under a lot of pressure, and patients are coming in every day.
>> Howard Bauchner: Chris, you can speak for the, all of the U.S. There's no need to. I think people really recognize that certain areas of the South and then particularly Southern California have been difficult. But what's the last couple of months been like in Pittsburgh? Because you generally did pretty well during the so-called first wave in the spring, but what's it been like the last couple weeks?
>> Christopher Seymour: Sure. So, again, thanks for having us on, Howard. I would say that in Pittsburgh we're optimistic that our case volume is in its sort of [inaudible], sort of hopefully coming down from what was another peak in December. And this sort of likely reflected traveling around the holidays and gatherings. But it was, as Lennie has described, sort of the dominant reason for patients in the ICU and filling up the majority of our ICU beds a few weeks ago. But things may have plateaued a bit, at least in our area.
>> Howard Bauchner: So, Lennie, I want to go back to you. Chris knows that, you know, the early publications in the major journals, if you looked at ICU care and then you got to treatment, it was a potpourri. There could be like ten categories of drugs, you know. Antivirals. IL-6 blockers. Anticoagulants. Steroids. The list went on and on. It was really hard to sort out where we were going. Then, of course, there was the early notion about intubating early or intubating late or preventing intubation with different approaches to oxygen therapy. For the seriously ill to critically ill patient, where are we now? What do you think there's clarity with respect to standard of care?
>> Lennie Derde: Thanks, Howard, for that question. So I think the first major success was led by the RECOVERY trial in the UK, who declared steroids effective in their population, at least when they were using oxygen or more, as we say it. So including a critically ill population, though there was not a big group of those in that study. And then a couple of big trials stopped recruitment, including our Remap-Cap trial. And [inaudible] published that [inaudible] on September 2nd together with a meta-analysis that I think provides conclusive evidence now that steroids work for critically ill patients with COVID-19. So I think that got it started. And maybe Chris wants to follow-up with what we did since then.
>> Howard Bauchner: Yeah, so first, Chris, do you agree that corticosteroids now represents standard of care in seriously ill patients with COVID?
>> Christopher Seymour: Yeah. If they're sort of that first building block in our wall of treatments, it is the biggest and the most sturdy. That is what we go to first in patients, particularly those with severe disease. I'll add one comment, Howard, that I was thinking, as you asked the question sort of describing the spring and sort of many of these issues that relate to delaying intubation or oxygen therapy, some of them actually weren't necessarily related to physiology but, because at the time we were worried about ventilator shortages and availability of PPE. And so some of those clinical decisions may have been guided by trying to limit aerosols or, you know, get head of the disease that we didn't know much about.
>> Howard Bauchner: Right. But it did appear from the early data, after people were intubated, it was very difficult to get them off the mechanical ventilation. So I think that's, so, one, I do think it was a reflection of concerns about shortages of ventilators. But also then I think clinical data emerged to say, if you can, if you can prevent ventilation or if you can prevent the use of mechanical ventilation, that would be helpful. Before we get on to other therapies, Lennie, what's your approach around trying to avoid intubation? Are you trying to avoid intubation in Utrecht?
>> Lennie Derde: Not too much. So I think in the beginning there was a lot of fear of, you know, aerosols and spread. That was also increased by the fact that we sometimes had shortages of PPE. We don't have that problem anymore, so now it's easier to think, you know, about the patient only. And so I think, if you can get by without invasive mechanical ventilation, that's superb. But if you delay intubation too long, the patient will suffer.
>> Howard Bauchner: Are you using proning?
>> Lennie Derde: Yes, definitely. That's our first go-to therapy as a rescue therapy if they don't manage on kind of spontaneous breathing on the ventilator. And I think most of our patients, like over half are proned in the early stages of their ICU admission.
>> Howard Bauchner: They are. Chris, can you reflect on what Lennie just said. Is that similar in Pittsburgh?
>> Christopher Seymour: I think so. And, you know, that's, it's a familiar treatment in the ICU. We've known for a decade that prone positioning can change V/Q matching and improve oxygenation and outcomes in patients with severe lung injury. And so it's just become more common now in patients with COVID. I would agree that we go to proning perhaps aggressively in our patients in Pittsburgh. And we see far more patients proned when I walk down the hall than I would have two years ago. It might be a different story in those who are on the ward and sort of awake proning. There's interesting data about that. But that's not become a definitive part of our practice yet.
>> Howard Bauchner: So let me draw out some scenarios because that make it's more real. So you have the seriously ill patient in the intensive care unit. You started them on steroids. You're not quite sure that they're getting better, and they're not intubated. What's the next treatment that you think about? Lennie, I'll start with you.
>> Lennie Derde: So I think, so for the listeners, we have a preprint out last week.
>> Howard Bauchner: Right.
>> Lennie Derde: That shows the results of our analysis of the use of tocilizumab and sarilumab in critically ill ICU patients on organ support. And of these patients on organ support, all but 3 out of more than 800 were on respiratory organ support. So about 30 percent was high-flow nasal oxygen, 40 percent NIB and another 30 percent were invasively mechanically [inaudible].
[ Multiple Speakers ]
>> Howard Bauchner: Thanks.
>> Lennie Derde: And we showed a substantial mortality benefit. So for me, critically ill patients on steroids, when they are admitted to ICU within 24 hours, that's what we did in the Remap-Cap study, received either tocilizumab or sarilumab. So I have to say it's preprint, so it's not peer reviewed. It's not been published in a peer-reviewed journal. But I know the data inside and out, and I know the robustness of the results. So I already trust it, and I've implemented that in clinical care. And we're seeing that, not just in my hospitals, but in hospitals across the Netherlands and other countries. Chris, I don't know what you think.
>> Howard Bauchner: Lennie, just one question, and I do want Chris to comment because I'm sure he's read the report and is familiar with the study. A difference between those two drugs? Is there any reason that you would choose one versus the other?
>> Lennie Derde: No, I actually don't think so. We chose both for scarcity issues. So there was a difference in how we implemented it in the study in that, for tocilizumab, clinicians were allowed to give a second dose within 12 to 24 hours if they had the feeling the patient was not improving clinically. There was just a one-off dose for sarilumab. But they are both IL-6 receptor antagonists. And we actually used a lot of technical borrowing in the design of the study. And so I think the result applies to both of them together.
>> Howard Bauchner: Chris, your comments. I know you know the study and the study results.
>> Christopher Seymour: Yeah, so I'm also a coauthor.
>> Christopher Seymour: So, but if I take off the author hat and maybe I put on the hat I wear right now for "JAMA," it's interesting. You know, this isn't the first paper on tocilizumab.
>> Howard Bauchner: No.
>> Christopher Seymour: There are many studies that we've reviewed at our journal as well as many other, whether it it's the "New England" the "Lancet," "JAMA." They all have, seem to have a library of papers on toci, but they're all different. Different designs, whether they be placebo controlled or not, if there's concomitant therapies that are being administered. And this is sort of the lifecycle of the pandemic. Many of these interventions, such as toci that were tested early on were not being administered with corticosteroids. Whereas, later in the year, we're starting to see combinations of therapy. So it's complex. There's no right answer. You know, you took a viewpoint that we wrote a few months ago, Howard, about being sensible in sort of how we.
>> Christopher Seymour: Adopt new evidence.
>> Christopher Seymour: In whether intervening quickly or sort of, not necessarily a nihilist, but taking your time. And I wrote that because I'm sort of in the middle. I'd love to see more data. And we know there are other platform trials testing these drugs. And, you know, there's scarcity. So we don't necessarily have a lot of this in the U.S. right now, so it's not part of our clinical practice yet.
>> Lennie Derde: I think it's a very interesting question, Chris, about the steroids. So I fully agree, you know, we'd love to see more papers on critical care patients. But most of those trials were in ward patients and without steroids. Do you think, you know, there's a reason, that's the reason for the difference?
>> Christopher Seymour: Well, it sort of makes the Remap-Cap trial innovative and unique in that we're reporting on severe populations, most patients who already been receiving glucocorticoids. So I think that's new information, and there's a lot to discuss.
>> Howard Bauchner: Lennie, so let's back up. So the patient arrives in the ICU, and the two of you are caring for that individual. So it feels like steroids, and then there's this discussion about these two IL-6 inhibitors. And I think people will, some will wait to see the results of the publication, the formal publication. Others will adopt it now. In that same population that you're caring for, and then I want to back up. When you get the phone call from the ward, so the, what can I do to prevent the person from coming to see you? But let's put that aside for the time being. Anticoagulants were in many of the early papers. And then there were some reports that there were side effects from the anticoagulants. Chris, starting with you, any sense of the anticoagulants?
>> Christopher Seymour: Sure. So I think this area of research is been driven and has a lot of interest because we see coagulation abnormalities in these patients. There was a beautiful sort of review that we published a few weeks ago on arterial and venous complications in COVID, and it's real. When you round on these patients in your unit, you're seeing maybe more DVT's or arterial thrombi that you hadn't before. And so there's good scientific rationale to move forward with trials of systemic coagulation and then, as we move out of the ICU, different approaches to prophylaxis. And you had mentioned side effects in some of these trials. Well, yes, there will be side effects when you give a blood thinner. But the question is, is whether those side effects are balanced by the potential benefit to the patient from the drug? And so, yes, so there has been actually a coalescing, I think, of a lot of groups in this regard. Something that we haven't seen before in science, which is a multi-platform, randomized trial. Meaning the coming together of a platform in Canada, the Remap-cap platform worldwide, as well as federally funded work in the U.S. by the NIH, something they call the ACTIV-4A trial. These groups actually have harmonized who they're enrolling, their outcomes as well as the DSM-V for, these three groups are working together to understand the best way to treat patients with, for example, Heparin.
>> Howard Bauchner: Lennie, status of anticoagulation for you?
>> Lennie Derde: I think Chris nicely summarized. So these three groups together have just concluded in our platform that therapeutic anticoagulation for the critically ill patients on organ support does not work. So we think that it an answer. But I think it's just, you know, the start of a whole lot of more questions, because I can really relate to what Chris said. We're seeing a lot of thrombosis, arterial and venous. But the question is, what's the best approach for that? Is it anticoagulation? Or is it maybe antiplatelets? Or is this maybe something that's mainly driven by the immune system? And are the immune modulators the answer to this question? I think we really don't know, but it's a very, very interesting field.
>> Howard Bauchner: A question has come in, and it led me to what was going to be my next question. So what about preventing patients from getting to you? I mean, that has been the goal. There's been a number of reports on monoclonal antibodies. "JAMA's" just finishing up another publication on monoclonal antibodies. We also published a study that got quite a bit of attention about the use of a very specific SSRI, which people thought we should have been, Chris and I wrote the editorial note, that a number of people felt like we were too conservative in our recommendations about it's use. And I've gotten quite a few e-mails about that. But again starting with you, Lennie, prevention of patients moving into the ICU. Convalescent plasma. SSRI's. Monoclonal antibodies. What's the collection of options that you see as being viable?
>> Lennie Derde: It's always difficult to comment on care outside the ICU [inaudible]. But I think, you know, again, the first brick in the wall is steroids. You know, it's very clear from the meta-analysis that patients, you know, with, receiving oxygen or more benefit from that. I find the antidepressants very, very interesting.
>> Howard Bauchner: Yeah.
>> Lennie Derde: You know, it's always difficult if you're not completely immersed in a study to say, you know, this is definitive proof. So you kind of, you always want the second study to prove the first one. Very interesting. So anticoagulation may be helpful there; we don't know. But I think the multi-platform RCT is well on the way to providing at least, you know, some more questions or beginning of some answers for that. Support of care, we shouldn't forget, you know, in the ICU and also outside the ICU, that's an important part of our daily work. And I don't think there's one single bullet. It's probably, you know, the combination of everything. Convalescent plasma is a very interesting one. That's not a very simple intervention because the intervention depends on kind of the levels of antibodies in that plasma, even, you know, the mutant or the variant of the virus that the person donating the plasma has, you know, gone through. And there's all these things that I don't know a lot about because I'm not a hematologist. But just to say, you know, that's an intervention very, very different from just giving steroids. So last week in Remap-Cap, we have sent out a press release that, in our study, in the critically ill patients, convalescent plasma did not give a benefit to the patients included in the trial. But, again, that leads to a whole other set of new questions on, you know, which subgroups could potentially benefit. So that's a question that's still unanswered.
>> Howard Bauchner: Yeah. So I just want to clarify for our listeners. Embedded in my question were actually sub-questions, which are, you know, are we talking about the moderate to seriously ill? How do we prevent them from progressing? Or the mild to moderate and, how do we prevent them from progressing? And so the convalescent plasma that you mentioned didn't work in seriously ill patients, but that does not mean it may not work in mild or moderate to prevent progression. Chris, your sense of prevention of having patients move into the ICU, where do we stand with what information you've seen?
>> Christopher Seymour: Right. So, well, what's moderate, Howard? And what's mild?
>> Howard Bauchner: Okay.
>> Christopher Seymour: I think one of the interesting things throughout the course of the year is that the labels we're putting on patients and how they match up with the different trials has been changing. And so what the FDA, what the WHO or what one trial group may view as an amount of organ support corresponding to moderate or severe, it's a little different. So you have to be mindful of that in the evidence. So I guess this brings up remdesivir. This is the drug that's been tested and recommended particularly, by the NIH, to be considered for patients who are in the hospital as a way to prevent deterioration and perhaps improve outcomes. We've been talking about remdesivir now for months. Initially, it was, well, is there an issue of scarcity? And that's sort of been tempered. But its effectiveness as a combination drug in the mild to moderate population, I think, is still where it might have a place and where it's being used at our center.
>> Howard Bauchner: There had been early reports, Lennie, particularly around remdesivir, but that its use outside of the U.S. was incredibly limited. Is that your impression, that remdesivir is not being used widely in Europe?
>> Lennie Derde: So it's not being used widely in the Netherlands. There's some use in wards. There's hardly any use in critical care units. That's because of the evidence, but also because of the very, very limited availability. If you look at the preprint about tocilizumab and sarilumab, you will note that about 30 percent of patients got remdesivir as a treatment. So in the UK, I would say that there is some use in critical care of remdesivir.
>> Howard Bauchner: What do you think's going to emerge around critical care of these patients in the next three or four months?
>> Christopher Seymour: Well, I'll, so the crystal ball; right?
>> Christopher Seymour: I don't know that, well, we're not at liberty to talk about some things. But we do know that, when there is evidence put on the preprint or sort of this medicine by press release, there's always going to be science behind that. And so looking forward to both the Remap trial of the IL-6 antagonists plus other platforms that are studying that drug. The definitive trial on systemic anticoagulation that we talked about from ACTIV-4A attack, those are forthcoming, and I think will be practice changing. What I'd love to see is us move towards, I think, this fascinating paper that was in "Science." And it came from the group at Penn and many others. So we're looking at different immune phenotypes based upon a whole sort of multiomic readout of these patients compared to folks who got better as well as controls. That type of heterogeneity has been an interest of the scientific community in sepsis, but it's still there in COVID, even though it's just a single pathogen. Meaning all of our host response is actually, it's quite different, and that's not surprising. But how one trial may find an effect from tocilizumab, whereas, another doesn't.
>> Christopher Seymour: Very well might relate to the design or relate to the, you know, the specific on the surface of what the patient looks like. But far more likely it's what's going on under the surface with some of these immune phenotypes. That's what I hope we will get to.
>> Howard Bauchner: Lennie, what do you think the next three or four months will bring other than the publications of these papers that are in preprint or press release?
>> Lennie Derde: So I'm actually really looking forward to changed collaboration without just focusing on a single drug. Because the things like we've done in the multi-platform RCT I think are very important. So I have a feeling that during this pandemic we have moved slightly towards kind of this learning healthcare system that we would maybe want. And combining, you know, clinical data, mortality data with phenotypes or even endotypes of patients because that will give us the detailed answers that we are looking for. I think the most interesting development kind of related, therapeutics is, you know, I think at the start of this pandemic, at least I would never expect to get two immune modulating drugs and not an antiviral are kind of the first to pass the post for being effective in at least critically ill patients with COVID-19. So immune modulation in pneumonia is a very interesting subject. And I think we're going to hear more about it without, you know, being able to look in my crystal ball and tell you which one will work. Because if we knew, we wouldn't have to do the trials.
>> Howard Bauchner: That leads me to a follow-up question, and you touched on it. What surprised you about this disease, Lennie? What, when you look back, you go, that's just unusual or surprising. I spoke to the head of the FDA advisory panel the other day, Arnold Morrow [assumed spelling], and he was just, and it was around vaccines. But he just talked about the surprises that the disease has offered, particularly asymptomatic and pre-symptomatic spread. But let's put that aside. What, when you just step back as a clinician taking care of many patients with this disease, what have been the surprises?
>> Lennie Derde: So I think the first thing that's surprising is that it takes people a while to get ill enough to be admitted to a hospital. So it usually takes about a week.
>> Lennie Derde: And then, you know, without knowing the specifics of that, it seems like people in the beginning of their illness suffer from the virus. But then, you know, after a while, you know, by the time they end up in critical care, they don't suffer from the virus as much. They suffer from this augmented reaction of the immune system, and we know a little bit about it, but we don't know, there's also a lot we don't know yet. And I think that is very surprising, and it's different. And the other thing that surprises me clinically, and I don't have any research experience in that field at all, is that it's so hard to wake them up. I don't know Chris recognizes this. But, you know, usually when somebody, you know, improves on a ventilator, you just, you know, you wake them up and they come off the ventilator. But it seems to take ages for these patients to get off the ventilator.
>> Howard Bauchner: Same question to you, Chris. I mean, you're one of the world's experts in sepsis, which is, people have always used as, that's the parallel condition. You have an enormous amount of experience, both of you, around taking care of patients who so-called are septic. What surprised you so far about just the clinical condition?
>> Christopher Seymour: Right. So maybe not as a sepsis researcher, but as the intensivist.
>> Christopher Seymour: Yeah, I guess I've been surprised to see, because I wasn't taking care of patients with H1N1 or, you know, the previous SARS virus, is that just the significant and severity of the lung injury. It's a simple answer to your question, but we're really giving a lot of support to these patients. And it is just unusual and a bit of a reset to think that you're going to walk into your place of work and care for six people that are proned. It's just very different. And that may speak to characteristics of the virus, maybe the host tolerance, but then also the aggressiveness of the host response. It's been fascinating to think about as a scientist. Very difficult to handle an intensivist. And, of course, challenging for all of us, you know, as parents and our family.
>> Howard Bauchner: Just a couple more questions. I suspect you have less experience with this, but, again, many issues cross my desk every morning. And when the term, people who've listened to these have heard me say it numerous times. When someone first said to me, what about "long haulers"? Chris has heard me say it. I go why are we talking about truck drivers in the United States who drive all night? Then they had to tell me, that's not what they were talking about. We still have very limited information about what this phenomena is, how many people are actually affected by it. Certainly there is a whole group of people, Hallie Prescott and Derek, who have written about post-ICU patients, particularly those who were admitted for sepsis. I'll reverse it, starting with you, Chris. Any instincts or notions about the so-called long hauler syndrome?
>> Christopher Seymour: I don't know. I'll tell you my thoughts, Howard. So the data we've seen so far about long-terms or cognitive, functional and sort of hard to describe symptoms after COVID has been from cohorts that often are not evaluating these patients beforehand. Whereas, in sepsis and in other critical illnesses, we found that there are distinct changes after the incident. But we really have to know where the patient started. So I don't know yet if this, the sort of symptomatology that we describe in the long haulers or the long COVID is actually that different than a bad case of bacterial pneumonia. In part because that research just is still forthcoming. I think we're hearing a heck of a lot more about this because there's way more people that are getting COVID. And so the frequency of these issues in our population is much, much more common than perhaps the elder with bacterial pneumonia, who then is not themselves six months later.
>> Howard Bauchner: Lennie.
>> Lennie Derde: Yeah, fully agree. And also, I mean, there are reports of kind of post-viral illness and stuff like that. And so I think, you know, for that long COVID research, it would be good to kind of look across our discipline, look at people who have done, you know, comparative things in viruses other than the SARS-Cov-2. But, yeah, there's a lot to learn. And it's a significant burden for people who go through the disease.
>> Howard Bauchner: Lennie, over the last now year, sadly, year of the pandemic, you know, death rates in the U.S. have been extraordinary. England just reported out the highest, I think the largest increase in deaths since World War Two. The U.S. has yet to report out. Although, Steve Wolf in our pages has estimated it will be close to 500,000 excess deaths of which about 350,000 will be attributable to COVID-19. Obviously, much of this depends upon coding, which is controversial. That's why excess deaths may be a better measure. Where are we with mortality? Has it come down? And how, what can people expect if they, if a loved one goes into the ICU? What do you think current mortality rates are? I know it depends on the patient and their age and their comorbid conditions. But has it come down? And where do you think it's settling? What are the projected mortality rates?
>> Lennie Derde: So all the things you say are true. I do think we've reduced it a little bit. But, yeah, it also depends actually on surge. Because, you know, because of surge there may be a, you know, we don't like that, but it's hard to take care of 80 patients with nurses sufficient for 24 beds in my case. So I looked up the mortality figures for the RECOVERY trial.
>> Howard Bauchner: Sure.
>> Lennie Derde: And for their invasively mechanically ventilated group, the mortality was 41.4 percent, and it came down to 29.3 percent. That's 28-day mortality. So that's around 30 percent. I think that's just, you know, slightly lower than the control group in the toci paper from the Remap-Cap study now. So I do think there's been some progress. And if I look at the national data for the Netherlands, the mortality kind of overall is between 25 and 30 percent. Obviously, your worse off if you're older.
>> Howard Bauchner: Chris, what's your sense of mortality rates?
>> Christopher Seymour: Yeah, same thing. When we used to give sepsis talks to have folks, sort of lay folks, not healthcare workers, sort of remember, we would say, one in five don't survive. And that's what I would come back to again, noting that the [inaudible] balance is changing. But it's probably a little bit more, particularly because it's mostly elders who are getting severe illness.
>> Howard Bauchner: And then the last question for the two of you, I pray that this pandemic will be behind us in September. I don't know when, it could be July; it could be September. Obviously, the rollout of vaccines is going to be critical. And, obviously, there's increasing concern about what it means for low- and middle-income countries, the three of us don't live in a low- or middle-income country, but the availability of vaccines in low- and middle-income countries. And neither Moderna or Pfizer are going to be very successful in those areas in part because of the distribution requirements for those two vaccines. So I think people are more encouraged to either see J&J. And then the somewhat discouraging report from China about their two vaccines. But let's say, God willing, we are behind, the worst is behind us by late spring, summer, fall. What are the long-term lessons? What about how to do clinical research? I mean, do you dismantle these groups? You know, people have touted the extraordinary science that's led to vaccine development in record time. I think some of the recent trials, most conducted outside of the United States, have really advanced care. Do, what happens to the trialists that have done all this sort of work? Lennie, I'll start with you because you've been a key mover and shaker in some of these studies.
>> Lennie Derde: So I touched on it before, but I really think we should keep the collaborative spirit that's there in the international research community. And I think adaptive platform trials, of which Remap-Cap is just another example. There are many adaptive platform trials. Like Derek Angus, your Derek says, you know, you don't build a stadium for just one game. We have a huge stadium now, so we should use it to our benefit and keep researching respiratory infections in the ICU. And I think there are many questions to be answered, even in that specific field. So I hope we continue that. That's the long-term vision. And it may well be that, even though, you know, we get out of this tunnel and we see light at the end of the tunnel now, COVID's or SARS-Cov-2, I should say, could stick around as a cause of respiratory infections for which people can get admitted to the ICU. So keeping the collaboration, keeping some of the speed and keeping some of the transparency. And, you know, whether that should be science by press release, I hope not. But, you know, transparency does have advantages. I looked at a paper from "JAMA" from February, not too long ago, because I wanted to use it in a talk. This was about the speed of science.
>> Lennie Derde: And the February, you know, this figure. I've never used, outdated less than a year after it's publication, you know. Science is just, the speed is amazing.
>> Howard Bauchner: Yeah. Chris, what's your sense, you know, as the pandemic settles, particularly in those countries that have participated in these research paradigms?
>> Christopher Seymour: Yeah. So I think, as a research community, there's been a very, very deep sense of altruism, right, that we are in this together to help others and urgently. And that's led to many of the sort of, the phenomenon that Lennie's described, which is that these large platforms are formed. The platforms are coming together. They're sharing data before publication. They're aligning DSM-V, steering committees, working across borders. This is unheard of when we're competing, when we're competing for the first paper on the subject in "JAMA." And it's not just to compete for the pub; it's because then that leads to funding. And then more, you know, life is a competition in this way for many academics. And I think my own reflection is that we've been able to turn off that gene a little bit during the pandemic. And I hope for most of us it stays off.
>> Howard Bauchner: Well, I actually, I've said this before, I go to many of the ICU meetings, that I feel that the critical care community is as good, if not better, than any other community in trying to understand what would be best for patients and trying not to relate so much to their individual careers. And I think the last six or nine months has epitomized the best of clinical research. And so I think the critical care community should be congratulated in trying to understand what would be best to advance care, and let's think about other issues later on. And I know there's a lot of complexity in international trials and harmonizing protocols and DSM-V's and ethics committee. And certainly as an editor of what I hope is an influential journal, journals have also tried to figure out ways to adapt to publishing in a very different era. So I think people know all of our content is free. We will publish major trials in literally a week or two weeks or three weeks, not two or three months. I think, in general, for many articles, preprint service has served us well. Although, I still think there can be a robust debate about publishing by press release or by preprint server. I think for certain studies, I think there may be better or different approaches. This is Howard Bauchner, editor-in-chief of "JAMA." It's been Conversations with Dr. Bauchner. And we've returned to what was the focus of so many of the early conversations, critical care of patients with COVID-19. I've been joined by Chris Seymour, an Associate Professor of Critical Care Medicine at UPMC, our Associate Editor in Critical Care Medicine. And Lennie Derde, who's an Assistant Professor at the University Medical Center in Utrecht and has been an important Coordinating Investigator of Remap-Cap. Thanks to the two of you. I wish you well. Stay healthy, and I certainly hope that the two of you have been vaccinated. Take care.
>> Christopher Seymour: Yes, thank you, Howard. It's been a great chat. Bye, Lennie.
>> Howard Bauchner: Bye, Lennie.
>> Lennie Derde: Yes.
>> Howard Bauchner: Take care.
>> Lennie Derde: Thank you.
>> Howard Bauchner: Bye, Chris.
>> Lennie Derde: Bye.
>> Howard Bauchner: I'll speak to you in an hour.
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