AHLA's Speaking of Health Law
AHLA's Speaking of Health Law
COVID-19’s Impact on Clinical Research
In this podcast, Amanda Coulter, Coppersmith Brockelman, Clint Hermes, Bass Berry & Sims, and Joanna Bergmann, Northwell Health, discuss the impacts of the pandemic on clinical research, both in the short and long term. The podcast also looks at the expanded access pathway for unapproved drugs, biologics, and medical devices, and COVID-19 vaccine development.
To learn more about AHLA and the educational resources available to the health law community, visit americanhealthlaw.org.
Okay, well, I will start things off. My name is Amanda Coulter and I am an affiliate attorney with a law firm, coppersmith Brockleman PLC in Arizona. I specialize in clinical research, contracting and compliance, and the majority of my clients are research sites and investigators. Um, primarily community based, but a lot of academic medical centers as well. And I have 10 years of experience representing an academic medical center, so I understand the site side pretty well. Um, but I think that our conversation today will, will all be trying to talk about the perspectives of everyone involved in clinical research, certainly. And, um, I'd like the co-presenters to introduce themselves mostly so that I don't butcher your names by accident.
Speaker 2:Okay, cool. Um, so my name is Joanna Bergman. I'm a Senior Associate General Counsel with Northwell Health, uh, located in New York. We are, um, a very large health system, um, in the New York City metropolitan area. Uh, my primary role, um, with the Northwell are two support the fine Scene Institutes for medical research, which is our research, um, unit. And I also do a lot of work supporting our telehealth team. So we were obviously very active, um, during the time of covid, which is obviously still obviously still going on. Um, but there were definitely some hot areas and, and you know, we can definitely talk about sort of my experience there and the questions that we came up with, um, and the things that we're still really thinking through right now, just in terms of maybe figuring out what we did right, what we could do better and, and how to prepare for, um, the next wave should it happen, or the next pandemic or crisis should that, uh, come about. Um, Clint, uh, you're up.
Speaker 3:Yeah. So my name is Clint Hermo. I am currently counsel at Berry in Sims. But from the end of, uh, I think it was 2006 up until the beginning of this year, I was general counsel of, uh, two different academic medical centers, one in US and one overseas. Um, and at, at various points along the way, I've had operational responsibility, um, actually for, uh, IRBs and for clinical trial regulatory affairs. Um, but I think that right now might be the most exciting time in my career to be in this field. So I'm psyched to be with both of you today to talk about this
Speaker 1:<laugh>. That's true, Clint. This is an exciting time. That's a positive spin, um,<laugh>. Um, so, alright, now that you know who we are, since we have revealed to you that we are lawyers, and this is for a group of lawyers, I think it's appropriate that we give our disclaimer. So I just wanna remind everyone who's listening that these opinions are our own. They do not reflect the policies or the positions of our employers or our clients. And we're participating in this podcast, um, for informational purposes. And it's not legal advice. And I also wanna say thank you to a H L A for highlighting this topic. Um, cuz I know that the, for the three of us, this is our world, but we think it's important to bring to light just the breadth of the impact that the pandemic has had on clinical research. So with that, I will give you just a, a very brief map for what we hope to cover today. Um, we wanna talk about the immediate and short short-term impacts of the pandemic on the clinical research enterprise, um, and world in the United States and a bit globally as well. How the regulators here in the US and possibly internationally have responded. Then we wanna talk a little bit about some emerging long-term impacts that we foresee changing how we, uh, provide and participate in clinical research in the United States as a result of what we've experienced. Um, and something, I know there's been a lot of, um, new information lately, even maybe in the last week, the expanded access pathways for unapproved drugs, biologics and medical devices. We also wanna talk about the current pace of the clinical research going on today and the impact, perhaps of the quality of the scientific results of that research due to the pandemic. And finally, hopefully ending with a bit of good news, um, how, what's going on in Covid 19 vaccine development. All right. I'm going to start us off talking about the impact of the, what is commonly referred to as the coronavirus or covid 19 on clinical research, particularly in the United States. So I think that everyone probably knows that like the rest of the world, there was an immediate, an emergent response, uh, from clinical researchers sites and sponsors and regulators initially when the country sort of slowly shut down. And I will say, Joanna, you know, you hinted at this, but you really are in the thick of it in New York where we know was really the first epicenter in the United States other than, well, actually Seattle, but it seems like the scale was larger in New York. So you're particularly Yeah. You like to figure better in New York<laugh>. Um, well, you know what, you did, you did, right. Go big. Mm-hmm.<affirmative>
Speaker 2:It. You're absolutely, I mean, you're absolutely right. I mean, as I was sort of reflecting on this conversation and just sort of the last several months, you know, what sort of continued to sort of jump out at me was sort of how quickly, um, you know, everything stopped and then everything restarted. You know, we maybe sort of turned 90 degrees and redeployed, you know, our resources, our people, we were all at home. But definitely people, you know, those of us who just sort of work at their computer not to be at home, but obviously everybody, you know, on the ground, um, just had new sets of needs. There was, you know, we had to deal with the existing trials and the existing things, you know, new things had stopped, new trials were no longer going to sort of be, be implemented. Yes. Um, we had existing trials that needed to be handled, and obviously we had a huge batch of, of people who, um, needed a response, these covid patients, um, and everything, you know, was kind of geared towards, towards that. And, and what does that mean? I mean, you know, this will probably be a recurring theme for me as I keep talking about it, but, you know, this is a situation in which just about everything that was done was to some degree experimental or investigational. Um, and so I am newly the FDA lawyer's good, um,<laugh><laugh> because of all the e u a stuff that, that we had to work on that I'd never seen before. But yeah, I mean, the speed with which we all kind of pivoted, um, and sort of reallocated ourselves was quite, quite impressive. Um, and pretty intense.
Speaker 1:So that's a good segue because I think, um, you know, there was this immediate response, and that's partially what I wanna talk about initially, is we, we all, the nation, when I say we all, everyone had this, you know, momentous event in our lives where we, in clinical research included, where we all stopped and, you know, no one was going to the hospital, um, unless you had to, um, you know, I live in a city with an academic medical center, and it everything stopped except for who was going to the hospital. And so that, you know, the sites were impacted, the sponsors were impacted, the studies were impacted, the subjects were impacted. They, there was an immediate, you know, stop of enrollment. There was a temporary stop in, um, visits and continuing in existing studies. Um, but as we talked about in preparing for this call, the, all of these changes really differed based on where you were, uh, and what, whether you were considered a hotspot, whether there was, you know, an outbreak. And I heard recently, um, a pharmaceutical, a global pharmaceutical representative, um, state that, um, initially all the studies stopped for them, but that 95% have actually resumed for this one pharmaceutical company. Now, what happened between March and today, July 24th, is, you know, how did we go from that immediate stop to resuming potentially 95% of this pharmaceuticals, you know, portfolio of studies to start with? Not all the studies stopped completely. I mean, there are certain therapeutic areas where, um, you know, oncology and cardiovascular research, particularly the ones that come to mind for me, where you had patients that couldn't stop completely, but that doesn't mean there weren't changes in how the studies proceeded. Um, and, you know, how the sites enrolled, how the sites engaged, how the sponsors engaged, and all of that. Um, so I think that variability and the initial kneejerk impact, you know, we, we might see in waves and certainly if you, if you have other, uh, ideas, let me know. But I think we'll probably see them in waves. Like, for instance, um, in Texas right now, you know, I know that there's just as one example, they're probably feeling much more like New York did a few months ago, whereas in New York you might be feeling a bit of relief, but this might come and go for the short term future. Thinking
Speaker 3:About that. Yeah, I, I, I think that's right. And I think it, you know, it it, you know, there's the, there's on the one hand, there's the impact on studies that were underway when, you know, when, when the lockdowns all happened or when, you know, when you get another wave of something ha you know, in a, in a particular geographic area. Um, but there's also, you know, I mean, I, I am worried about, um, new trial enrollment in, in general, and I just heard of something I, I think it was just today or maybe yesterday, but the National Cancer Institute had said that enrollment in trials has been dropping by about 10% every month since the pandemic started. Um, and that's, you know, that's catastrophic, really.
Speaker 1:Yeah. It's long-term effects. I, I don't think we're gonna know what the long-term effects on research, uh, globally are in the US are gonna be. But I know that we're some organizations, I think N C I is one of them, um, are starting to develop, uh, statistics and monitor what the impact has been on research in the us. So I think it'll take us years to figure out, you know, how how far did this set us back. Another topic we wanted to talk about were how the regulators or the, the entities that govern research have responded. Um, you talked about nci and I know that, um, NIH issued, um, information for their NIH applicants and recipients of N NIH funding, and some, you know, fairly detailed FAQs about the quote flexibilities that they would be showing, um, related to the, their sponsored research. The, uh, US Department of Health and Human Services office for Human Research protections also issued policy guidance. But that really came after, if I'm remembering correctly, the FDA's guidance and the fda, I, I couldn't even begin to list out all of the guidance that's come out. It's sort of like the land of the Fast and the Furious<laugh>, you know, I feel like these email alerts I keep getting there are, there was a guidance and then it was updated, and then it was updated again. So there's been guidance on convalescent, plasma and, um, development of course, and licensure of covid 19 vaccines. Um, there've been some nitty gritty guidance on statistical consideration for clinical trials and the IRB review of expanded access requests. But the, the bread and butter of the FDA guidance on clinical trials is their guidance that was originally issued in March, titled, let's Catch You title, FDA Guidance on Conduct of Clinical Trials of Medical Products during Covid 19, public Health Emergency. I lost count how many times they updated it, but I know it's been several. And the last update was July 2nd. And that guidance. Yeah, they've been, they've been busy. They've been so busy. And that guidance, I, I feel like it has been helpful. I mean, it was, it was written primarily or directed supposedly at study sponsors. Um, but really, I think there was some good information that came out that sites and investigators and IRBs and sponsors could all use as they thought about how do we pivot? How can we continue with research? You know, so things about things like, um, submitting protocol deviations, amending the protocol, um, documenting, you know, events or changes in processes in the clinical study reports. Um, and addressing some of the emergent and immediate problems that the subjects had, including how do we get product investigational product to the subjects? Um, what if it's an infusion, for instance, can, is there another site where you could provide an alternative infusion? Um, how can you monitor the sites where the monitors can't physically access them? So what were the remote monitoring options? So I would encourage anyone that that is either dabbling or working in this sphere to go through that f d a guidance. I don't wanna read it all, but, um, I thought that it was helpful. And I, I, I don't wanna read it all again, I should say I've read it many times. Um, I thought it was helpful. I found that my clients found it helpful. But I'm curious, you, you both Clint and Joanna, did you also see it as helpful?
Speaker 2:I thought that, I mean, all of the guidance obviously was overwhelming in some respects. And so, you know, to the extent that yes, you had a specific question, you know, it would, it would sort of important to sort of tailor your focus or your search. Like, you, you, you, like, I, I had an ex, I had a thing that I did every day, which was, you know, refresh on the, the FDA and, and make sure that I was just aware of everything that was, was kind of coming out and then able to sort of isolate which ones seemed most relevant to my work, and then the work that was happening sort of at, at Northwell. Um, and, but so I knew that like other things were out there, but there were a lot that I didn't read. You know, you just sort of like, it's almost just issue spawning the guidance, be like, oh, there's something there. So if a question comes up, right, I'll go look at that<laugh>. Um, you know, in general, I, I think about some of the guidance around research as, as maybe highlighting processes that were in place for deviations that had all of a sudden a new kind of significance, maybe, maybe a provision or something that really hadn't been used because they didn't have to be. And so it was just kind of, oh, oh, right, we are supposed to report these things, or we're supposed to mm-hmm.<affirmative>, you know, do you know this is a deviation. Oh, okay. You know, um, but we definitely, you know, um, you know, had a very kind of comprehensive and quick response to making sure that, you know, with respect to the kinds of in-person activities that could no longer happen, um, onsite, you know, making sure that we had documented and, you know, we'd turned a policy in weeks, you know, um, had a alternative ways to do consenting, right? Because even if you're re doing the research with the Covid patients, um, can you go into the room like all of our, you know, hospitals, all those sites were, were, you know, not locked down. We were obviously going in there, but they were contaminated in some ways. And so it was very hard and very important to keep people safe and, and keep that distance. Um, so we very quickly had to put together processes and policies and make sure that those got communicated out. Um, you know, I think if it doesn't come up later, we certainly talked about this before, also, the notion that you had a lot of people who maybe were in the research space historically, and so had some familiarity with these regulators, these kind of guidance that it's, it's likely that Overp was going to have put something out or go to FDA to see that. But then you also had this whole slew of people who sort of all of a sudden found themselves in some kind of a research space who maybe didn't even know that, you know, there were guidelines and rules and where to go. And so, you know, so you're kind of updating people who were familiar with it, and also trying to grab a whole new set of people who, um, were in novices. Um, and, and again, you know, with everybody kind of all over the place physically, you know, the communication channels and making sure you grabbed everybody was, was really important. Um, but yes, we spent countless hours looking at different guidance documents, um, and, you know, between federal and state on all manner of topics probably produced as law firm lawyers will sort of be proud of, you know, hundreds of pages of summaries,<laugh>, so that we had a, a place to go and, and could track what we were doing. Cuz our advice could change, like within a matter of days, we could be saying one thing in the guidance changed and we were saying something else, and we were very mindful that there's a real potential for future audits and, and inquiries. And so, you know, it's just, it was very important for us to document everything and know why we were doing what we were doing and what we were saying, because, you know, there's a lot of things that were going on, very dynamic space, and, and we were all doing the best we could, regulators included, to keep up with it. Um,
Speaker 1:Yes. But yes, and they really were very intense. They really were. Yes. It, it has been intense and it has been dynamic. And I, I think that was a great word that you chose, but I also think it's, um, interesting because we can't look at all of these as interim necessarily, even though mm-hmm.<affirmative>, you know, fingers crossed this pandemic is hopefully interim<laugh> in the broader trust
Speaker 2:Also that the federal, that the federal waiver has been extended for another 90 days.
Speaker 3:Yeah. Guess. Yeah. Well, the emergency has. Um, and so that, yeah, so that, that, yes,
Speaker 2:That
Speaker 3:Thankfully also gives us all the, all the emergency use authorizations and everything else have, have, have all been extended in the Prep Act and everything else. Yeah.
Speaker 1:Yeah. So I mean, so it's, it's true that these, these were written for the purpose of addressing a temporary problem, but I think, well, we all think that some of these changes may likely be permanent. When you think about, um, maybe the benefits that we've seen in clinical research. So I heard someone say recently that yes, from now on, uh, protocols will be written to be pandemic proof or to address, you know, potential future major events that might disrupt traditional in-person clinical research visits and monitoring. But in addition to that, there are likely to be process improvements really, um, where maybe there have been some, well, I think there have been some underutilized, um, like electronic formats or, you know, um, platforms or tools in the research sphere that perhaps researchers and study sites and sponsors have all realized, Hey, this is actually pretty great. And how, how, Joanna, do you think, um, research is likely to permanently change as a result of some of the temporary changes we've implemented because of Covid?
Speaker 2:Yeah, I think, I mean, I think you're, you, you're sort of right on in terms of where I would predict or foresee the changes to be made sort of more permanent, both kind of at a practical level and a regulatory level. I mean, we're definitely nervous overall about making sure that whatever gets, um, restored to pre covid times is something that we are aware of and can kind of return back to, right? I mean, it's, it's, you know, it's like turning the ship around. I mean, it takes<laugh>, you know, it'll, it'll take some time. But I do think that, um, that the, that the, the, the shift, um, and reliance that we all had to put upon use of electronic technologies, remote, um, communication devices to, to sort of continue to operate, whether it is as we are doing in, in sort of over the phone conversations, whether it's the doctors sort of having all these telehealth visits, whether it's the researchers as, as you started to talk about earlier, um, doing remote monitoring, remote auditing. I, you know, again, I mentioned remote or electronic consents, all these sort of different ways to leverage technologies, you know, whether they were, you know, non-existent or nascent at different institutions, I think will definitely, you know, have definitely taken a hold and will be, will be exploited. Sounds like the wrong term, but you know what I mean,<laugh>, um, used, um, in this space going forward. Uh, you know, I, I think one of the challenges that, that sort of I'm having we're having, just as we think about that right now, is what I perceive as a kind of an unusual position that was taken, um, with respect to HIPAA compliance and some of these technologies, the, the, the OCR sort of, um, enforcement discretion position that they took. Like, you know, we think you should do your stuff using HIPAA compliance tools, but we're not going to, you know, put you in HIPAA jail or whatever if you use something that's not HIPAA compliant. Um, during this time for me, you know, in my position was kind of a complicated message to<laugh> the nest, um, within the system because again, we don't wanna create sort of habits where we'd have to, you know, end them. So, um, I'm hopeful that y you know, both as a regulatory matter and sort of an operational matter will kind of expand our resources in that space to continue to, um, enable these kinds of, of things. Um, you know, we're seeing new options coming through from sponsors in terms of moving data around and, and certainly, you know, we're exploring a lot of different platforms for, for communication. So I definitely think that's an area that will be here to stay. Um, and I think that's, that's good. I think that's good. It does. The other thing that I think, um, again, sort of the, the lawyer, um, you know, ask getting questions or being nervous is, um, you know, with the ability to do things from a remote distance or not in person, you know, we do, it does raise some concerns about state licensure laws or things about, you know, if you're gonna be recruiting somebody from another state, what sort of issues does that raise in terms of your ability to sort of be operating in that space, either without a license if you need one or, or, or whatever. So, so these are some of the issues that I think are animated by that move, um, that we're kind of keeping track of and, and on top of. But, um, but yeah, I think that's, that's the space that's, that's with us. I don't know, Clint, if you have any other thoughts about that one, um, or Amanda?
Speaker 3:Well, I, yeah, I mean, I, I, I, yeah, I think a lot of these, I, so a lot of my practice historically has been in the field of sort of glo you know, international research collaborations and, and, and global public health. And so a lot of these changes if, you know, if, if they sort of permanently take hold, you know, I think we'll continue to facilitate global research collaborations. Um, and so I, yeah, I, I, you know, I agree with what you said Joanna, about stuff that is, you know, seems, seems likely to outlive what is hopefully the temporary pandemic. But, um, I, I'm also curious like what, you know, what, what do you, you know, Amanda or Joanna, what do, what are, what do you, what do you think are maybe some changes that we're seeing now that that shouldn't be permanent? I mean, so for example, are you seeing, um, uh, you know, people, for example, maybe try to bypass going to the IRB for, for, for changes to study procedures because you know, it's an emergency and, and, and is it gonna be hard to pull them back when it's not an emergency anymore?
Speaker 2:I, this is, uh, I'm not aware of, of that particular, um, um, but I probably wouldn't have said I was aware of it if I were<laugh>. Um, But, um, it's an interesting question. Um, I guess the first thing that just comes to mind is, is kind of consistent with maybe some of the, the press that we've been seeing just around the, and, and this is in sort of institution specific or research specific or protocol specific, this kind of, um, how fast everything kind of happened, um, and, and how many sort of inputs we all had in terms of we should do this or this is the next best thing. And, and so, so I don't know. I mean, again, I know that for, for us, we have, you know, we had an obligation as both researchers and healthcare providers to, to sort of be responsible in this space, right? And, and, and we had a lot of sort of patients and a lot of people wanted data and, and, and, and an opportunity to sort of maybe test to their product, um, or their, their, their solution or treatment. And, and so, you know, we had to come up with a system pretty quickly to sort of evaluate that and decide what we would do and what we wouldn't do. And, and again, there are a lot of people who were clamoring for, for some kind of access. And so again, this sort of goes more to the kind of thing I think will stay in place, which is just sort of a better system for evaluating things that that's not sort of a regulatory thing. But I do think that we have a, a new sensitivity to sort of ways in which research can get, um, maybe compromised might not be the right word, but just sort of informed and, and sort of mutated<laugh> with, with, you know, when, when politics and, and, and sort of, um, just a lot of media inputs and sources were, were sort of coming at us. Um, it was just really rapidly changing and we were all just sort of trying to do it and everybody kind of had their idea as to what the next best thing would be. I mean, we're all sort of panicking and sort of being calm would, would, was sort of a virtue. Um, you know, I I, I'd have to think about that question a little bit more. It's a good one. Um, cause certainly we should go in the cookbook of sort of what to do next time and what not to do. Um, but, but nothing else is sort of springing to mind. I don't know, Amanda, if you have thoughts.
Speaker 1:Well, I was just saying that, um, it may need to stay in the, that cookbook, you know, as you say for a while, because I also worry that we don't know yet what sort of, um, bad habits are being developed necessarily<laugh>. So I would be interested to hear in six or 12 months what, what sort of a knee jerk reaction and changes happened that, you know, we later found out, Ooh, that maybe that wasn't so great, and, uh, here's what we're gonna do instead.
Speaker 3:Yeah. I mean, we we're watching in, in a way, I, you know, it, the FDA's been busy cranking our guidance, but we're also watching the FDA learn in real time, aren't we?
Speaker 1:Yes. Everything's happening in real time and you know, even though it feels like it's been five years since the start of the pandemic, it's really been, you know, depending on what you believe, it's really been about six months since, you know, really the earliest of the Scott and people's radars. So we are in the beginning of what is a much longer than we wanted to be processed. And that's an interesting space to be, like you said, Clint, it's an exciting time.
Speaker 2:Yeah, I mean, I think one of the things that, you know, again, I sort of going back to what we are sort of thinking about now as a system, um, and maybe a process improvement. Um, and I know we sort of kicked this Terry A. Little bit, um, but it is interesting when everything you're doing is, you know, in terms of treating patients or, you know, trying to manage the situation is, is to some degree or other just experimental or investigational, you know, we've got, we had just a flood of, of compassionate use and expanded access requests and, and you know, I think it was just, it was a really novel space for people to be in. And like I said, it's just people who didn't necessarily, hadn't ever been in that space before. So we're definitely thinking about, um, ways to, and I think we did it, I'm, I'm still trying to figure it out, but the rapid training of, of people so they know what resources are available and, and, and also making sure they all get routed to the right place. I mean, I guess I'm sort of obsessing about the process, um, on my end, um, just because the information just sort of comes in, so you just need to kind of deal with it. Um, but you know, again, it happened all so fast and so dynamically. Um, anyway, I interrupted you. What were you gonna say, Amanda<laugh>.
Speaker 1:Oh, no, that's fine. I think you're right. I think that, um, you know, these other, this is something actually we wanted to talk about. It's, um, we've been talking about the long-term impacts, but we did wanna talk about the expanded access pathways for unapproved drugs, biologics and medical devices. And I'm curious, uh, Clinton, Joanna, you know, Joanna, you mentioned that you've had to out of necessity really address these issues as counsel more often. And Clint, have you also experienced that?
Speaker 3:Yes. Yeah, for for sure. Right. I mean, you know, so, um, I should, should we say, should we maybe say a little bit about like what expanded access is or?
Speaker 1:Yes, yes. It's probably better not everyone will be so in, in, have their practice be so in-depth clinical research like
Speaker 3:We do. Yeah. Well, okay. Yeah, I mean, so, um, I mean, cuz I certainly, when, when, you know, when I have been working with, you know, at, uh, uh, hospitals and universities, I, I definitely find it like a range of familiarity with, with, you know, this sort of the different concepts here. Um, and, and you know, and I think as you, you've both alluded to some, there are some people that are, that are by necessity having just, just now getting involved in this space that haven't historically been in it. Um, so, you know, for anybody who's unfamiliar with what expanded access is, um, there's various ways that patients can get unapproved drugs or devices. Um, so, so approved drugs and devices, um, can always be used off-label, but the distribution of, uh, unapproved drugs and devices is, um, restricted and just can really controlled by the fda. And, and, and so one way patients get these is as part of a clinical trial, right? Um, but that's not the only way. So like pre c i, I probably would've told you that the most common or the best known non-clinical trial mechanism for patients to get unapproved drugs is through like a treatment i n d where you get the FDA's permission to use an unapproved drug for a particular patient or a group of patients in a, in a structured way, but you're doing it for treatment and not as part of a research study. And then, um, you know, another alternative non-clinical trial mechanism that we've all become much more familiar with in 2020 is the FDA's Emergency Use Authorization Authority. Um, and so these are more of like a, a blanket permission to make a particular unapproved product available in certain circumstances during a public health emergency. Um, and, and, and, uh, you know, I I I, I, I think there is, um, you know, maybe particularly with respect to treatment INDs, because the IRB has to review the consent and, and, and, and grant approval for a treatment I n d I think there, there is a little bit of a, of a, of a spectrum or a little bit of a blurring in people's minds between what, what amounts to a research study and what amounts to a non-research way of getting access to a an investigational product.
Speaker 1:That's a good point. Joanna, have you, um, have you encountered that personally?
Speaker 2:Yeah, I mean, I, I'm definitely in my head, I'm aware that there can be the disconnect. I don't, you know, I'm not dealing directly with sort of patients and communicating those messages, but it's definitely something that we've been thinking about. Um, you know, especially given this hybrid space, I mean, we are definitely familiar with compassionate use requests, the sort of one-offs or maybe the group kind of, um, programs that, that, that drug companies sometimes put into place. Um, and I think for us, I mean, the novel space for me this time around was sort of finding, and again, this isn't, I mean, I guess it research ish, right? But, you know, we were, we were in the business of, of trying to figure out how to 3D print our own, like nasal swabs to, to do testing and like 3D print our own, um, kind of some device accessories so that we could, um, kind of ensure that enough ventilators would be available, whether it was like through a, I mean a splitter or kind of a, a, um, an adapter. So, so for me, I mean, that was just totally novel space. I mean, cause if it's medical device, it's it's manufacturing. It's this e u a process that I don't know that anybody really knew about. I mean, it's just sort of accessing this sort of process and application and just sort of working through that. I mean, it was very interesting. Um, and well,
Speaker 3:And I don't, yeah, and I don't think, oh, sorry. No, go ahead.
Speaker 2:I didn't really have anything sort of more to say about it so much as it was just really an interesting space to be in. Um, and you know, so far we've been pretty successful. Um, but the eua
Speaker 3:Yeah. Yeah, all I was gonna say was, um, was like your, your point about 3D printing, like, you know, components of complex things or, or, or, or nasal swabs or, or, or what have you, made me think about the fact that like, you know, of course as, as the pandemic was taking off, we, everybody was sort of desperate and, and some people still are to find P P E, right? Um, and, um, I, I think that very many hospital lawyers did not necessarily realize that the FDA regulates even surgical mass as medical devices. Um, and, and so there were, you know, a lot of these, a lot of these guidance documents that are coming out from the fda that people, you know, people were, people hadn't otherwise had much contact with the fda. They now were all of a sudden having to look, um, having to look on fda.gov for, for, for a way forward.
Speaker 2:Yep. It was pretty intense too. Um, and I definitely, I mean, we were all over the news at various points, um, you know, working with the, the governor's office, um, and really trying to sort of advance some of this stuff and fill in some of the gaps. Um, so it was pretty cool. Um, we'll see how, how that goes. Again, I mean, to, to the earlier question, we, we were sort of talking about what happens like when the, the emergency period ends and when all of these things kind of go away. I mean, that's also sort of an interesting question that we were dealing with. Like, is my eua gonna be good when they sort of issue a new emergency declaration, you know, after their elap? Like just like kind of interesting things, like mm-hmm.<affirmative> put a pause in that and then like, it comes back<laugh>. I don't know. You know, because, and I think the interesting thing for us also was that the, the nature of the eua, um, and how it applies to other users, and if I'm making the thing and using it myself versus I'm making the thing and sharing it with a third party or selling it, and what are, what are the rules that kind of flow with that? And you know, and then when we were looking at like esi and that was, you know, all of a sudden had an e uua and instructions for use and what does that all mean? Like all of this stuff. I mean, again, I'm just sort of back to the thing, it just changed so quickly all the time. And so you get something in your hand one day and use it, and the next day the rules change and you can't use it. Um, you know, it's just really, and these are not rules that people were kind of necessarily familiar with in the first place. It's just really interesting.
Speaker 1:Yeah,
Speaker 3:The patient, I mean, so everybody's, every you hospitals are now using, um, uh, boxes of, uh, hydroxychloroquine from the strategic national stockpile to, um, you know, like, uh, uh, as like door opener, door stops,
Speaker 2:<laugh>, but I don't even understand, like I didn't even, I don't even understand like what it means to come from a stockpile, like who, so when someone just, when it goes out or just shows up, like, how did it get here? What did we agree to? What does that mean? Like, there was just so a lot of these things that, you know, maybe we agree
Speaker 1:To return it. Yeah, I know, right?
Speaker 2:Nevermind
Speaker 1:We have to return it. Yeah, exactly.
Speaker 2:Yeah.
Speaker 1:So the pace, the pace of the changes, um, you know, we've, we've mentioned several times already, it's just been dizzying. Um, what, what do you both think about how that pace has potentially affected the quality of the science, um, for either covid specific research or non covid research? You know, do you have an opinion about whether either the pace or the intense media coverage over everything happening? Um, you know, I, I think that in some ways, you know, I've heard interesting information about researchers finding better ways to collaborate in real time about the results that are coming out. Um, either reviewing, you know, one example was, um, reviewing results and discussing them over Twitter in real time.
Speaker 3:Yeah. I mean, Twitter, you know, so, so it, this is, I, you know, I think this is really fascinating, right? So, so for a while, you know, predating the pandemic, we've had these Preprint servers, um, but I don't, I think that hardly anybody who was not, you know, like an actual scientist had ever heard of a preprint until now, and, and, and, um, you know, and now you've got like, like preprints are making news and, and even like, I, you know, I, I just think this is fascinating. So like, even before somebody issues a preprint that, you know, just even just the press release headlines from the study, um, makes, makes news and actually influences clinical decision making. So there was, I think there was like a whole week where all we had about the recovery trial was that dexamethasone was useful for particular patient population. There was no, like, it took a, it took a week before there was even a paper on Preprint, and that paper still hasn't been peer reviewed. So, um, you know, so the, the, I mean the, the, the, the pace is is, uh, you know, as I think you have both said, the pace has been intense. Um, and, and the media coverage, I think, you know, particularly of the, some of the pre-print stuff has not always been really good. And, and in, in a way, thank God we have Twitter, because I think a lot of peer review now is just happening on Twitter. Um, and that's how you get these, you know, sort of immediate, you know, publications and then very quick retractions from like places like the New England Journal Medicine and the Lancet,
Speaker 1:Right? And, um, also we've, I think we talked about this, um, previously just with each other, the impact on the patient preferences. So, um, you know, are we finding that patients come in knowing, Hey, I I want you to try X on me, or I want to get access to y
Speaker 2:I think there's a whole level of sort of, you know, yeah, um, aggressive, maybe not the right word, but sort of more informed or more sort of focused, um, advocacy either at the patient's level or, you know, uh, of a family or, or relative for sure. Um, and I do think that complicates things a great deal. Um, cuz I don't, it, you know, it's hard to say. It would be hard to say, well, you could say, we don't know if this works, but you can't say definitively, we know it won't work. Um, and I think the pressures all over the place. Were y you know, pretty monumental at times. Um, so I do think that you have people, I mean, I guess you always have people coming in and having done their internet research right? And, and, and, and have some ideas about what their diagnosis is or have an idea about what they want, right? And so that's, that's not a new kind of thing, but, um, but all of the information coming out and sort of being unprocessed and all that stuff, like, I definitely, I think we definitely saw that for a period of time.
Speaker 1:So, um, you know, and that leads into the last thing we wanted to talk about were just sort of the, the vaccines that are in progress. Um, Clint, what do you know about the FDA evaluation of the vaccine?
Speaker 3:Yeah, I mean, I'll, I'll, so I've, I've spent a lot of time on, um, have been spending a lot of time on vaccine research and, um, and, and of course this is like, this is one area where you would worry deeply about the quality and pace of science. Um, yes, uh, because like, you know, it's one thing to give a, it's one thing to give a drug to somebody who's sick, but it's, it's quite a different thing to, to give hundreds of millions or or billions of, of doses of something to, um, to healthy people. And I think people are, you know, people are nervous about whether the FDA is gonna be pressured to approve a vaccine before one's really ready, um, say sometime in October<laugh>. Um, and, uh, uh, you know, but, but I, I don't know, it was two or three weeks ago, the FDA issued this, this fairly detailed, um, guidance document about what it was going to require, uh, in order to approve a Covid 19 vaccine. And a lot of people, and I think myself included, were pretty reassured by that. Um, so the FDA gave really detailed information about the safety testing and efficacy measures, um, and, uh, including what the vaccine clinical trial endpoints would be. But the FDA also specifically addressed, uh, emergency use au, uh, u emergency use authorization. So the context of a Covid 19 vaccine. And they said they wouldn't issue an e uua until, um, the safe, uh, you know, essentially until the safety and efficacy studies had been done. And so really you'd get an EUA just in that period between when you had phase three studies done and when the, when the sponsor had submitted and FDA had approved a biologics license application. So, so you, you know, at least if the FDA sticks to its, its stated standards, you wouldn't get a, like a premature emergency use authorization.
Speaker 1:Well, that's good.<laugh>. Well,
Speaker 2:On a high note, I
Speaker 1:Was just gonna, I wanna remain positive here. So let's, let's end with, um, some reassuring news from the FDA that at least at this point, they don't feel the pressure<laugh><laugh>
Speaker 2:That they intend that their vaccine is gonna actually work.<laugh>.
Speaker 1:Yeah. Fingers crossed.
Speaker 3:That's the plan.
Speaker 1:Yeah, it's a good plan. Well, um, this has been really fun. I know that, um, we wanna acknowledge that this is only a very high level discussion of how COVID 19 has impacted the US clinical research space. Um, we probably used a lot of acronyms without explaining them, without really noticing that we were doing it. And, um, many listeners may have questions perhaps about specific topics. And I want to encourage anyone that you can reach out to us. And I know that the three of us are happy to answer any questions people may have. And I wanna thank the HLA for inviting us to participate in this discussion.
Speaker 3:Absolutely. It was fun.