CRO and Clinician Insights — A Pathway to Streamlined US Feasibility | LSI USA '25

Lisa Boyle  0:05  
Good morning. Everyone delighted to be here and working and presenting with Dr Nicholas amoroso, an interventional cardiologist from musc we are going to talk about the need for re feasibility studies in the US. We're going to go through some of the issues that you would currently see, that people are enduring, and we want to talk about some solutions that we have. And hopefully it will be a nice interactive session, and you get to ask some questions and we answer, you know what I mean, and give you some some advice. So next slide.

Okay, so the FDA EFS program allows early interactions between developers. So again, why us? EFS studies matter. We wanted sponsors to be able to interact with the regulatory bodies like, you know, early and often. And the FDA allows, allows that with their early regulatory engagement, the having, having early feasibility studies in the US, gives us access to leading medical institutions and their expertise. And as well as that, what you might see is, is that the physicians working in those institutions also have collaborative interactions with FDA. They're known entity, and the FDA is mean, is encouraging that conversation I know Nick is going to go through again, how he works with that and give us more insight there. And one of the competitive advantages of conducting BFS in the US is it positions companies for early market adoption. We have engagement with the payers, the providers, and a successful US based EFS can facilitate downstream investments and partnerships. And I think again, for startups, I'm talking around this for startups, we're seeing that the EFS you need data to actually get your device or your product on the market. Clinical studies are actually very, very expensive, and the the way that we can, you know, to mean, help that is, it's, it's like a catcher Institute. But the way we can help that is having the successful interactions with FDA, having successful physicians work on your behalf, and then build that credible, FDA reviewed data set so that it will help you in the long run, would help you work with the investors. Say, Hey, I have good data like, you know, fund me again, and you can go on to the next phase. EFS provides real world insights into device performance and helping companies optimize their design before the costly pivotal trials, and that early clinician and patient feedback reduces the risk of device failure and increases that likelihood of commercial success. The nice thing that the FDA has done is this, 60, 6060, they want to implement a 60 day IRB, a 60 day first site activation, contracting and a 60 day to first patient in And historically, um getting contracting and site initiation has taken up to 11 months. So this is something that you know, to me, FDA is trying to streamline and recognize that you guys, probably, you know Will, Will will say, Well, why don't we go all us, or things like that. So this is what the FDA is trying to is trying to streamline. What we have is regulatory challenges. We all hear about the regulatory pathways and getting more and more complex. The need for data is is higher, and the burden is always on. Is on the sponsor, as I just said earlier, the high cost and the limited funding. So it's that catch 22 situation. You need the data to get the funding. You need funding to actually execute on the trial, and that's even before you go to patient recruitment and site selection. So again, what are the sites? What is the patient population you're trying to target. Do I want to have sites that will give me excellent quality? Do I want to be thinking like think evidence generation? What do I need to get and then what am I going to do with that data when I get it? And as I said, the lengthy startup time sometimes sites, it does take up to 11 months, and where it falls down is in that contracting space. And again, Nick is going to Will she will share more on the contracting space. Do you want to feel free to jump in anytime, and then we have the reimbursement and market access uncertainty. So unlike the later stage. Pivotal trials, the EFS studies, they don't generate the data that you need in order to get CMS approval. And I know, if you were here for the last talk, they were talking about, you know how the regulatory pathways and the CMS approval is working and operating, but there's a lack of that clear reimbursement pathway for the innovative technologies is often very discouraging for the startups. Do you want to?

Nick Amoroso  5:26  
Yeah, so I'm kind of curious. I was trying to read everybody's badges around the room here, and it's pretty hard to see. So show of hands. Who here is in a med tech startup company right now? Okay? And then anybody here, kind of in the research and regulatory support organizations, CROs and the like, no, okay, larger companies that are looking at perhaps acquisitions, no or okay. So that kind of gives us an idea of the audience, and I think that's what Lisa and I have been targeting with this topic now for a while. This isn't the first time that we've had these conversations, and what we hear time and time again from sponsors or startup companies big and small, is needing successful partnerships with physicians and with sites. There's some very basic things about that. Obviously, you need doctors and sites to perform the research to get your evidence, but there are key characteristics of those entities that make it fruitful, make it useful and make it cost effective, too. So you know, look, thinking from the clinicians perspective, when I'm approached by a company or what have been good interactions from sponsors, we have to think of a few things My partners and I, hopefully myself also, one we want to be practicing in your niche of medicine. So we need to be focused on what your topic is. Secondly, we need to be dedicated to and experienced in early clinical investigation without some experience in that it's a little bit of a unique territory that has other hurdles not typical for large clinical trials even. And the other is passion for innovating. So a physician who is passionate about innovation is going to be willing to take on the non billable hours, right? The extra work and effort it takes to identify these patients, hopefully create, right? They don't. They're not sitting around twiddling our thumbs typically, right? We have to create time and bandwidth to consult with you and provide you feedback. And those are things that without having a passion for it, there's honestly not enough incentive. Having done EFS and first in human implants before is really unique, as I mentioned, and you need to have staff as well as the physician who are accustomed to working in a gray zone, working expecting the unexpected to happen. So you know, having that experience is critical. You also want the physicians to be pioneering and not too risk averse, but still responsible, thoughtful and safe, so that they have credibility. And lastly, you need somebody who can present, who can publish, who can essentially publicize the good work that you and your company have done as well as the data that's been generated from it, and we see that has taken on a very different form now than it used to 10 or 20 years ago. It used to be that went writing papers, writing papers, writing papers, maybe posters. It does feel begrudgingly, more like it's, you know, using Twitter, using Twitter, using LinkedIn, but you know, conferences and modern methods of publicizing your work are important, as well as traditional academic pursuits to provide the FDA and other regulatory bodies data they believe in, but the physician doesn't Do it in a vacuum, and so having successful site partner is critical as well the sites, the institution, the hospital, the universities, they also need to be experienced and open to early clinical investigation. Remember, this is a money losing game for them, right? So it has to appeal to their mission of education and innovation, and if the site is not dedicated to those things, like many of other hospitals might be, it doesn't matter how clinically busy they might be and have as many patients as you could ever want in your particular disease process, they're not going to take this on. It's going to cost you too much, at least. Yes, so being dedicated to education and innovation, you need a place where what they're taking away from it is reputation and service to their patients and staff, where cache a is king, not cash. Those institutions also have to have IRB contracts offices and reimbursement analysis offices that are familiar with this type of work, it in large clinical trials. You know there is some money to be made in early, early clinical investigation. That's not very often true, and so they have to view it again as part of their mission and be willing to take that loss leader early on, to be involved the site also in being amenable to that thing should be a good partner in expediting the onboarding process, because what I hear from all of the small startups is that time is money more so than any of the large companies ever feel. Everybody wants things faster, but the difference between you being solvent or not may be months of onboarding for different sites. A good site will have resources and tools to help guide you, and so that may be things like contract templates, budget templates or expectations and open communication about how to start that you know from the perspective of partnering with a CRO like verenex, for example, then we know that they can provide regulatory strategy development and IDE submission support that allows early engagement so that you're doing it right the first time around, rather than having to backtrack and look for more data. And that's very helpful when it comes to your trial design. Ultimately, this reduces cost and should help optimize your funding strategies so that study design is cost effective, grants and other funding support are available to you, and there's that certainly portrays well to your investors. Lisa, I don't know, examples of other ways that you find beer and X has helped other investigators in that process. 

Lisa Boyle  12:23  
I think where we can, where we can be leverage, is we're all x industry people and coming in and sharing, you know, what the right pathways are, having the relationships with the physicians, having the relationships with the regulatory bodies as well, and as Nik said, understanding what your goal is, you know, to me, and be able to navigate that pathway, uh, most efficiently and appropriately. It's, it's always hard to go to a zero. And again, I've always been an industry, so this is my first time at a zero. And I've always hated using them being very, very honest, because it's like, why would I pay you know, to mean, can I can? Can I bring it in house, and I've grown up a little bit, and I've gotten the perspective of, you know, hey, they're there with they're the experts. You know, you're paying for their expertise. You're paying for their partnership. And they've done it for multiple customers. So they've learnings that they know the questions you don't even know what to ask. You know, we, none of us know what we don't know. So that's the way I would why I like thesis of veronix as well is because, again, they want to be the partner, as opposed to just the pencil pusher or the administrative supporter. They we have a lot of support to be able to give with the market access. Like, how do you how do you create your dossier to give to potential VCs or funders? You know, something to say, Hey, this is, this is a good shot. We have a good option. And then you can get on to do your early feasibility study and generate the data that you need. So it's, it's, it's money well spent. And I know, Nick you have, you have a commerce there coming up, as well as, like, you know, recognize what money you have, what and what you need to do, and then engage with somebody who has the experience to actually use that money efficiently and effectively for you.

Nick Amoroso  14:08  
Yeah, understanding your bottom line is really helpful. Yeah, helps you keep focus and perspective. Allows you to kind of cut through the nonsense, focusing on your bottom line rather than your line item is a good way to for everybody to try and stay flexible in your onboarding process. How do you identify good partners? Though, is anybody here currently in the process of looking at EFS in the United States or elsewhere, frankly. And how did you find these sites? How do you identify them?

You know, I think classically, we know there are certain. Name brand institutions that you go to with the expectation that this helps give you credibility, that they are institutions that can, you know, deliver the product. I can run the trial. They're also going to cost you a fair amount, frequently, and some of them are Expeditious, and others may take 11 months. I just think you were talking about to onboard, and that can be pretty demanding, I think, on a startup company. So there are other ways, and you're not the only ones who are looking at easy ways to identify good site partners or physician partners. There's heart valve collaboratory and the Medical Device Innovation Consortium. These are two separate organizations who are kind of multi stakeholder entities that are focused at promoting early clinical investigation and investment in the US. They're obviously the heart valve collaboratory is focused on heart valve disease, but there are others out there and neurosurgery and the like, and they're looking at ways to be better partners, also to advise FDA and CMS and to receive feedback from them, and then to receive input from med tech as well, big and small. One of the resources I know Lisa has been spearheading through MD IC is in fact, creating a list or a repository of investigators in the United States who perform EFS work, who have experience with this, hopefully, that would be a go to resource for companies trying to find sites and physicians to target to partner with. I think many of us go to academic conferences and where, you know, go to the session. At least we can identify people with like interests, but that networking doesn't always come with the same knowledge or data about what can these people do? What's their experience working in the type of trial I need? Professional societies haven't traditionally supported this kind of work, it's just not a priority for them. And so there are other physicians around the country. We've been hearing the same feedback from both startup and large companies alike, saying, We just need more partners who are interested, passionate and know what they're doing in this space, and can do it in a expeditious way. We've we've actually a few other physicians and myself have been trying to address this, and I think there's other efforts in different avenues as well in the country. But for example, we're a group of structural heart physicians, inventors and regulatory experts who our goal is basically to create a one stop shop for you to come and say, I've got this product. This is my idea. I want to I'm ready to go to clinical investigation. Can you help me? And hopefully, in doing that, you get a, for example, five physicians and sites right off the bat that we have agreed to and marketed ourselves as having expedited onboarding processes, have a clinical expertise and a consulting experience to help you do those things, and that cuts out months and months, if not more than a year, of you trying to vet and search for sites that qualify for what you need. It's still in the development phase. Actually, our we've been working on this idea the past two years, and we currently have clinical trial that we're working through to, you know, find where the kinks are in the process. But we're looking forward to this maturing and becoming a useful resource to our friends in Medtech. This includes other states around the country, as well as traditional or large research foundations and some of the maybe less thought of medium sized ones, and again, providing a different environment and hopefully nimbleness and cost effectiveness that you might not have otherwise found. So I think that sums up majority of Lisa and I's perspective on how CROs physicians sites can work, along with med tech and the sponsors to make EFS palatable, make it cost effective, and frankly, end up with a better. Your product at the end of your journey going into looking for clinical approval. I already posed the question, how many of you are looking at EFS, but maybe hesitated. I didn't get much response. So I'll move to the second one. What challenges or myths have you heard about working with a US Academic Center.

Lisa Boyle  20:29  
You're very quiet. 

Nick Amoroso  20:30  
That's fantastic. Everybody has had great success doing EFS in the United States. That's awesome.

Lisa Boyle  20:37  
I suppose. Does it resonate with you guys? What we're saying that you know to mean, historically, the US, US has been perceived as been just overly burdensome, and that a lot of sponsors are going, oh us like we have Australia, New Zealand, Poland, Georgia, like these are all well known countries that we know people have gone to to actually conduct their Early feasibility studies. And what we're trying to say is we know that exists. But have you thought about, okay, yes, you can get data. Is the data of quality that you need? Do you have or have you had problems coming back into the US saying, Hey, I've o US data? Will that be okay for a US submission? Are the physicians that you've utilized over there? You know to mean, are they known? Can they support your conversation, as Nick was saying, like, you know, are they credible enough over here to support the Hey, this is a good product. You're you know to mean, we can speak to it. We can evangelize for it. We can talk to our peers, you know, to me, and get them all to to buy into it, like, is that resonating? And then you have the cost of traveling over to the over to those overseas countries as well, to check in on the patients, to check in on the data, to do your monitoring, to do your auditing, in order to compile your package to be able ready for submission. Do you want to come to the microphone? If you don't mind? Thank you.

Audience Question  22:07  
My country, my company, is in ophthalmology, and we were looking at EFS initially, but we heard it was very challenging, because the FDA would be involved at the very beginning, and it would slow down the path. So we went o us to Latin America, and the challenges there, in terms of you mentioned 11 months, is that you've got to get in country regulatory approval and ethics committee approval. Yes, in the in country regulatory pool is opaque. Yes, it's not a two way communication path, and you do not know when you're going to get approved. And in some cases, you have to get in country approval first, and then you get ethics committee, ethics committee approval second. In other countries, it's reverse, yeah. In in if you think it's any faster than 11 months, it's not. Takes about a year, yeah, and then the cost. Some countries require CROs, which will double your cost. Other countries do not. So it's not a straight path of going out, out of country, but if you want to be successful doing o us, you have to write your clinical protocol according to GCP, yeah, because otherwise the data is useless.

Lisa Boyle  23:14  
Yeah, yeah. That's, that's excellent. That's good insight. That's what we're seeing. And again, I've been, I've been on the sponsor side for many, many years now, between Medtronic, Becton, Dickinson and yen evolve, and it's very difficult to to have the data set that you need. Do you know what I mean? And it is, it actually does end up being more costly, more burdensome and longer and you end up then having to go and sort of recreate the wheel when you when you're going into your pivotal which you need in the US if you want to us. Submission, because, again, you can only have, I think, 10, between five and 10% of your data coming from the O us and for us. Submission, so it's, it's, it does end up being costing, but I don't think people see that. And goes back to Nick's point. You just mean every day is $1 every you know to mean, and you have to be thinking about, Okay, where can I spend my money most effectively and efficiently so that I can actually get what I need? And I think that's where, you know, having, as I said, I don't like, didn't like using them, but having a zero that you can trust and partner with, having the CEO have those relationships, you know, should be involved in the MD. I see the collaborative that Nik was talking about, the heart valve, collaborative, knowing that they exist. Unit mean should speed up your time to actually unit mean be efficient and make the best use of your dollars. I have

Audience Question  24:33  
a question for you, with all the changes that are occurring at the federal government level and FDA, do you think there are opportunities to basically add value to EFS, make it easier? You know, because that would really speed up things for startups, because logistically going out of country, that's a huge challenge. Yes, it's like, you've got to get your physicians down there. You've got your devices imported into country. They've got a recruit patient. Instead are according to your protocol, and then still, people will question your data because you've done it exactly, and so they they'll still look for an FDA trial. So there's an opportunity, you know, with all the changes, for the FDA to really refine EFS, to make it faster, to get approval, and to partner with various institutions, with the US. Do you see that happening? I'll

Lisa Boyle  25:24  
start, and then you can, you can answer it. I do, what do we see with the heart valve, collaboratory and with MD? I see is they have FDA people, you know to mean, as part of those forms where they're saying, Okay, we want to focus on EFS. We want EFS in the US. How do we do it? So they're looking at, okay, we know IRB approval. It takes a long time. Contracting is the longest piece of that. So how do we get get more efficient? So identifying sites around the country and the physicians that we want to partner with and saying, Okay, come together with your templated contracting terms your unit, I mean your fast turnaround, like, you know, have a fast track for IRB submissions, and then again, it's, it's on us and and to be able to identify what is the right site with the physician that wants to be doing it, and the patient population that you need in order To recruit faster. So there, there's different movements going on between the zero, the sponsor, the physician, and the people at the sites wanting to get this done faster. So, and that's what Nick was saying, we're trying to build a website where we have that list of like working with the willing to say, okay, here is your standard contracts, here's your regulatory information that you need for every study that you do. So all the regulatory paperwork here are the sites that have said we're signed up. We want to be doing this, so use us. So if you've got anything to add,

Nick Amoroso  26:55  
yeah, and I think another spin on what you were bringing up was, how are recent shake ups to funding in federal structure may be going to present opportunities for this to get better. There's been a really my sense of it anyway, and I think many of us on the medical side feel that the FDA and CMS have become pretty progressive, right in their attitude towards promoting and adopting early clinical investigation. The 60, 6060, initiative is definitely part of that. And my, my sense is that where 10 years ago, doing this in Europe first was much more attractive. It's become the pendulum has swung the other way, and doing this in the US is now cheaper, more efficient, and will provide you a regulatory pathway to commercial adoption faster. I'm hopeful that that perspective and that attitude is maintained, I think as we go through this transition right now of federal support, it seems in everybody's best interest in the United States, for sure, I haven't heard yet kind of where this is all going to land after I think all of the commotion that's currently going on, so I'm curious to see, hopefully, that that that forward thinking attitude is maintained, right?

Audience Question  28:30  
I just want to say one thing, Morris, when you go, Oh, you s the burden, burden on pre clinical testing was less, and so that's the advantage, and because first demand data is key to get to the next step. If you don't have that, you're not going

Lisa Boyle  28:47  
you're not going anywhere. Yeah, 

Nick Amoroso  28:48  
yeah, yeah, 

Lisa Boyle  28:49  
It's very true. Thanks.

Nick Amoroso  28:50  
Thank you. Thank you. You know, and we've heard that from from other people in other conversations, or when we have a US companies come and approach us about running, running these trials or having, you know, I'm on some scientific advisory boards, talking to them about what is their strategy to us, adoption and an approval. There is a common misconception about how well US data is going to be received, I think a couple years ago, there was a slew, at least in the structural world of large compassionate use registry experiences. O us and companies were really banking on that counting for something when they came to the United States, and it was not met with the enthusiasm or acceptance they were hoping they had some impressive data from it, actually, but it did not. It was not accepted as clinical trial evidence. So I do think that planning for that ahead of time is. Saying this is going to cost me more upfront for my pre clinical testing data, for example, before I can run that trial here in the United States is certainly costly, but it may save you more money in the long run, if it's going to delay you another year and a half or two repeating the same study back in the United States, after you've done your US studies, I think several companies I know of have have run into that conundrum.

Lisa Boyle  30:30  
Anything else?

Nick Amoroso  30:33  
All right, well, we'll be around the conference room if you have other thoughts or questions for us. But thank you so much. Thanks for the examples and appreciate your attention. 

Lisa Boyle  30:43  
Yeah, thank you.