I'm Emily Zeitler, and I'm pleased to be joined by Paul Wong from Stanford to moderate the session on EP Collaboratory. And I'm asked to read that it's my pleasure to welcome you to San Diego and Heart Rhythm 2025, the 46th annual meeting of the Heart Rhythm Society. If you have not already done so, please download the mobile app and you can participate in live Q&A. There'll be a QR code put up here shortly, I think, and you can submit questions, and I hope you will. It's a small group here this morning, so I'm optimistic we can have really meaningful interactive discussion during and after the talks. We have just a star-studded panel here to talk about the EP Collaboratory, and I don't know. Paul, did you want to add anything before we get started? No. This session will be recorded, so we really hope that others will be able to hear this as well. Thank you. Okay. So first up is the very famous Dr. Emily Zeitler to talk about collaborative communities. Yes. So I'm happy to take off my moderator hat and put on my presenter hat and share with you sort of the basics behind the EP Collaboratory, or really not, actually not the EP Collaboratory. Collaborative communities in general, and I'm really grateful to Dr. Van Haer, who is here with us this morning, who I know is just itching to get up here and give this talk himself, but instead we're going to just abuse him with questions afterwards. But many of these slides, in fact, came from Dr. Van Haer, so thank you to you and to your other colleagues at the FDA for being so willing to participate in these communities. We know that it's a rising tide that raises all boats, and so we appreciate your engagement because it just benefits every member of this ecosystem, so thank you very much. I'm going to talk pretty quickly through this introductory set of slides because a lot of what I'm going to say is going to be covered in more detail by Pete and Jared and perhaps during our discussion. So I'll just give you basics of what the idea behind a collaborative community is. It's a continuing forum in which private and public sector members, which of course includes the FDA, work together on medical device challenges to try and achieve common objectives and outcomes. So these communities can be convened really, they tend to develop somewhat organically, although once in a while there may be one member of the stakeholder community that kind of encourages the development, and that's kind of the case, I think, what we'll hear about with the EP Collaboratory. There was a lot of momentum in other sort of EP-adjacent areas, and so it made a lot of sense for the EP community to come together and build their own collaborative community. So again, we'll hear more about that from Pete. And the goal in these communities is to address complex challenges in this ecosystem, preferably in the pre-competitive space, although not exclusively. And the idea is that we can achieve shared goals, shared outcomes, solve some of the challenges, and leverage some of the collective opportunities with the benefit of sort of multifaceted perspective. And there have been some successes in this and other collaborative communities, and I'll outline some of those in just a moment. This is the general idea, spacing notwithstanding. There's a number of stakeholders, of course, who are involved in these, many of whom are in this room right now, FDA, clinicians, academics, patients for sure, and payers. One of the models that the EP Collaboratory was built on is the Heart Valve Collaboratory, which has been very active and quite productive. The idea behind the Heart Valve Collaboratory is just what you might expect. These are interested stakeholders in the heart valve community. For all the same reasons that we're here talking about the EP Collaboratory, they've made some progress in the heart valve space. And here are some of the leaders in that group. Many of these names probably look really familiar. These are people who've been engaged in the medical device ecosystem and academic pursuits for many years. And from the FDA, Chengfu Wu and Bram Zuckerman, along with many others, have been actively engaged in the Heart Valve Collaboratory. One of their, I think, one of the achievements that they're most proud of in the Heart Valve Collaboratory is the work that's been done in early feasibility studies. And we'll hear more about that, again, from other panelists this morning. But the idea here was that there was a pretty significant loss of early feasibility studies from within the U.S. to outside the U.S. And there are clear benefits to moving early feasibility studying back to the United States, both from a regulatory perspective, from a scientific perspective, an ethical perspective. So the Heart Valve Collaboratory really led the charge in getting early feasibility studies, along with their FDA partners and others, getting early feasibility studies back to the U.S., removing obstacles, improving efficiencies in this work. And in fact, there have been good results. We're not going to get into the nitty-gritty about what's been happening in the EFS program for the Heart Valve Collaboratory right now. But suffice it to say that there are ongoing challenges, but the group is highly motivated to stick with it and try and address these challenges. But you can see that over the course of the early work in the 20-teens, there was a pretty significant improvement in the volume of early feasibility studies being done in the United States. And that was attributable, at least in part, to the work of the Heart Valve Collaboratory. Another example of this sort of paradigm is the Heart Failure Collaboratory, which has also been around for quite some time. The Heart Failure Collaboratory was sort of the genesis of it was a think tank in 2017, and the coming together of all of these stakeholders. So this is also a pretty organic development. And the Heart Failure Collaboratory has continued to be incredibly active and has been innovative in how they use this forum to bring about change in the heart failure ecosystem. So this highlights some of the priorities of that group, and they have really done a nice job of identifying different streams of work and have identified leaders within these streams of work and have been quite productive. They have really invested in multiple annual meetings talking about various topics that relate to the development of heart failure therapies. As well as a very impressive and inspiring commitment to training the next generation of investigators in the heart failure ecosystem. There is DSMB training, there is statistical training, really like the nuts and bolts of how to enrich the field of investigators for heart failure therapies, which of course has impact in other areas as well. Another one of the successes from the Heart Failure Collaboratory was the development of the Lean CRF, so bringing together medical device manufacturers, academics, and regulators to think through how can we streamline the process of data collection for clinical trials. And through very arduous and tedious work that I had the pleasure of being part of, coming up with a series of data collection forms that could be applied across clinical trials, again, to streamline the clinical trial process. And that was really, I think, time well spent and has been used now in some trials. I'll just move ahead to the vision of an EP Collaboratory, which, again, we'll hear more about, but this is, you know, it's not a brand new idea. There's been a lot of talk about an EP Collaboratory. I think I saw Ken walk in, so Ken Vilcek will talk to us a little bit about the HRS perspective on the EP Collaboratory and maybe a bit of the history about where this has come. There have been some fits and starts, for sure, but I think we'll hear from Ken and others about why now is the time. Early days of EP Collaboratory have been about building relationships, establishing a stream for early feasibility studies, and engaging in some endpoint definitions. And perhaps we'll hear from the audience or the panel about engagement with the pediatric EP community. It's another exciting area for the EP Collaboratory that's not listed here. And, you know, I think I'll just stop there because we have a lot to hear from our other panelists and, again, really looking forward to the discussion. So thanks very much for being here and let's move on. Thank you. Great, thank you so much, Emily. I'm Paul Wong from Stanford, going to talk to you about facilitating early feasibility studies. So, again, thank you to our FDA colleagues who have been unbelievably supportive, I must say, really just fundamentally so dedicated to this work and really advancing studies within the United States. So very much appreciative and acknowledge some of the slides, indeed, are from the FDA. So the concept of the early feasibility study is that it is a limited clinical investigation of a device in early development and really is focused on a specific indication, evaluate the device concept in a way that can be used iteratively to look at clinical safety and efficacy. It's typically designed for a small number of patients, typically in the range of a ten or so, with capacity to increase. So these are slides from the FDA, which I think are really telling and really very instructive. And that is really there are myths, right, that all the clinical assessments must be done before entering the early feasibility. Human studies, the first human studies, don't have to be EFS. Many times they've been done outside the program and then can then start as a true EFS program. One of the, you know, also key points is that studies that are used to support the submission may in fact be done at different stages and really appropriately stages, optimal stages, as we'll talk about in a moment. Ability to expand is really one of the, I think, beauties and really the great insights in how FDA has really just masterfully designed this. And as we'll say, as we'll talk about, the ability to expand and then in the entire journey towards a pivotal trial. And so this is really designed to really be efficient, allow for the clinical experience to inform the process, the development of the technology, and leading to full approval. So these benefits can't be, I think, overstated because they're really very substantial. And that's one of the things I think our job collectively today is to emphasize that early feasibility can facilitate the overall process. And that's really what we all want to see from an industry, patient, and provider point of view. So these early interactions, we think, can really be strategic, really allowing the proper testing at the proper time, and then really facilitate, since it's all one application, the pivotal trial. So that benefit, we think, can be very, very substantial and should be a reason why industry sponsors choose to go through an EFS. So one of our big messes today is really that. And so, as you know, one of the big parts of the ecosystem, how this gets delivered to patients in the United States, and really one of the reasons the FDA is so supportive and really has been part of the charge, you know, really led the charge in this mechanism, is that it will lead to earlier user, U.S. user experience, and therefore really improved outcomes for our patients. You've heard the reference to the MDIC, the Medical Device Innovation Consortium. They're a public-private partnership, really designed to foster the ability of increasing efficiencies and speed up the time for startup enrollment. So my colleague, Dr. Weiss, who will speak next, and Dr. Farb at the FDA co-wrote really the first paper about electrophysiology early feasibility and really gives us the outline of where we are and hope to go in the future. And so in talking about really where we plan to go and what our goals are, really to facilitate in the United States the ability to have additional EFS programs done here. So, and really have the breadth of clinical site participation. So in our journey, and again, really I can't tell you how FDA has been so supportive. There are a number of mechanisms that we wanna reach out to different institutions, but really because of the incredible support of Heartland Society, so we give them just, huge amount of gratitude in leading us. They were so generous to create a survey for us that went to, I believe, all members. And so as part of that, we've been in communication with those respondents and have done another sub-survey, et cetera. As part of that sub-survey, we've identified what we're calling pioneer institutions. They've expressed their continued and future interest in participating in EP EFS. They've identified a number of institutional champions and really started the journey towards a really facilitated early initial trial initiation. As part of that, again, we couldn't have done it without the FDA support. We've held a number of roundtables, both for sponsors and EP institutions. And so that leads us to kind of the different parts of where we're going. And so the first part is establishment of and identifying these early champions at sites. We think that's fundamentally quite important. We've identified an executive director, Dr. Meg Babakanian, who will be running the EFS program. And then part two is really the sponsor recruitment. As we've talked about, we're well underway. And then finally, the role of the MDIC will be to put these partners together, that is the institutions and the sponsors, to really foster what we hope will be a very fruitful process. So with that, thank you very much. And I'll turn it over to our next speaker, Dr. Weiss. All right, good morning, everybody. And thank you for joining us. And here we go. And so there'll clearly be some overlap in these discussions. This is a very focused, and the initiatives, obviously, have been working together a long time on this. And the bottom line is that the EP collaboratory is what has grown out of the early work in early feasibility studies through the Medical Device Innovation Consortium, and then evolved into what we currently have initiated now through the collaboratory. And again, the collaborative communities has really been a major focus of CDRH and their strategic priorities, again, with this overall goal of trying to facilitate timely patient access to high-quality, safe and effective medical devices. And importantly, again, a continuing forum bringing together the key stakeholders, public-private sector members, working collaboratively to achieve these common objectives. So it really is a unique environment where they can't sort of live at the FDA, can't live with a particular industry partner, can't live very easily at a particular clinical institution. The question we all face here is how do we bring all these stakeholders together to get this important work done? And the goals, as mentioned before, are really to develop the best practices and robust strategies for addressing challenges, to generate and evaluate evidence-supporting novel approaches, to disseminate this information and implement the actual solutions. And we'll maybe talk a little bit more about actually getting stuff to happen as opposed to just talking about it. And I think that's a lot of what's happening now. And importantly, along the way, to clarify the ill-defined challenges, generate consensus on the definition and scope of those challenges, and, of course, how to problem-solve at that point to improve the whole medical device development ecosystem, particularly in the United States. And, of course, the partners and participants and stakeholders here are the key. As I just mentioned, it's really bringing everybody into a single tent to have this opportunity to work through these problems together. So it does include the patients and care partner organizations, and that's something we probably haven't emphasized enough, but we have representatives from organizations such as StopAFib.org involved, et cetera, who really represent the patient perspective. And that's something that we have learned a tremendous amount from and probably should hear more about along the way, because, of course, we need to sometimes be reminded that that's what we're all here for, right? It's the patients. But along the way, we need to have collaboration with the hospitals, the hospital systems, of course, private partnerships such as Medical Device Innovation Consortium, trade associations, technology manufacturers, the device distributors, the CROs who help us perform the research study, professional societies, of course, specifically Heart Rhythm Society, which has been so instrumental, but also the payers and other state and federal agencies such as FDA, and international organizations. Of course, it helps everybody if there's more uniformity across the world in how this is done as well. So reaching out in that setting is important, too, and foundations and other non-for-profits. So, again, a little more detail about what Emily shared, but I think it's really key to emphasize this ability to put all the stakeholders in one place and have these conversations. So with that in mind, and after several years of working through Medical Device Innovation Consortium to push forward early feasibility study, the idea of bringing this a little bit larger to perform a full EP collaboratory really began to take form. The mission statement has been created, again, thanks to Paul and others involved with putting this together. And as always, this is an aspirational kind of approach to this, but this needs to also be the foundation of any effort. But the idea here is to be a dynamic, interactive, collaborative community of stakeholders under a single umbrella for the purpose of catalyzing clinical research, advancing regulatory science, addressing knowledge gaps, creating meaningful advances in our understanding of cardiac electrophysiologic disorders. And with that in mind, the collaboratory was created as a physician-initiated, patient-centric consortium, and again, I like how important it is that we're trying to put the patients up front, of the multidisciplinary, individual, and organizational stakeholders established to identify and address knowledge and evidence gaps and foster initiatives in the diagnosis and prevention and treatment of EP disorders, and to serve as an ecosystem to connect, collaborate, catalyze clinical research, create valued advances in the management of EP disorders for our patients. So, sort of in order of some of the key highlights then that we are focused on, number one is to connect the key stakeholders together under a single umbrella. So again, bringing all these together, and this is really where we are very appreciative of the Stanford Bidesign and Stanford Arrhythmia Research Institute for actually bringing, giving us a home, okay? And again, I wanna emphasize how important that is because we need to have a place to centralize, and by having some administrative support and a place that we can give a name and organize together has been a key part of moving this forward. And again, everybody then gets to meet under this umbrella, excuse me, in a very neutral territory, so to speak, and that's very helpful. And with this then we're able to collaborate through building these relationships with all the different stakeholders to advance invention, innovation, and patient care, as well as regulatory and implementation sciences. We wanna catalyze clinical research with a focus on the clinical imperatives and knowledge gaps, and to create bold and provocative initiatives employing advanced technologies, modalities such as artificial intelligence, deep learning, digital health, diagnostic sensors, et cetera. There's gonna be much more to come. We're really just getting started to bring this up to speed in the modern era of technology development in our field. The stakeholders, again, in this particular instance do include, of course, the academic institutions, the hospital systems and hospitals themselves, medical device and technology companies, both large and small. So the key stakeholder companies, all the big names that you're familiar with, but also our startup companies, which are so important as well. Federal agencies, CMS, and of course FDA. And again, we have tremendous appreciation. Much of this began because of FDA initiative. And so we appreciate the fact that some are able to be representative. We understand there's a little bit of change in their ability to be visible, but we shouldn't forget at all that they have been behind this and completely involved with this from the very beginning. And we look forward to more of that participation. Medical Device Innovation Consortium is a public-private partnership has been key. Patient organizations I mentioned before and Heart Rhythm Society in our case. And obviously this is just an example of the initial working committee, but it's spread across both stakeholders in all those areas that we mentioned, as well as many across various U.S. clinical sites. And again, just an acknowledgement really of our FDA partners. And you can see, of course, that the FDA partnership is almost as representative as much of the others in this list. So again, without going through any details, but of course, and some are able to wear their FDA hats in this room and others are not officially doing that here. So I do want to briefly mention the MDIC in a little bit more detail. This is a 501c3 public-private partnership that has been established to help promote many different areas of medical device development. And then one of the major initiatives has been the early feasibility studies. But they have all sorts of resources associated with this. They have over 900 subject matter experts to consult with them, 75 member organizations, and 50 active working groups in many different areas of medical device development. So when we talk about the EPC, which has been the acronym now, I guess, of the EP Collaboratory, I kind of laugh because that's just a recent development. It's interesting how all this is just coming along. Again, we've heard a bit already about the EFS initiative, so I won't go through it too much more detail. But again, the three steps. Identify the key clinical sites that will be our pioneer institutions who are EFS capable. Next is to identify and bring into the fold the device industry partners who are most likely to want to do EFS in the United States and provide that ability to them. And then match them together. Okay, it's really that three-step process, and we continue to move through that quite quickly. You're also going to hear a bit more in a second from Jared about another important initiative. And again, FDA came to us because all these stakeholders are under that one umbrella to move this forward. And this is actually the ARC, the Academic Research Consortium, that has been put together to look at atrial fibrillation device development endpoints. Progress focusing on advancing the development and standardization of clinical trial endpoints for atrial fibrillation. Obviously of tremendous importance to the whole field. And I don't want to steal Jared's thunder other than say it's been organized in three separate working groups. One looking at safety endpoints, one looking at efficacy endpoints, and then trial design optimization and common reporting forms. The key activities that convene these multidisciplinary working groups, including clinicians, regulators, and industry representatives to achieve consensus on these endpoints and really drive forward what will be, we hope, the future of defining device development, not just in the U.S., but worldwide. And it's actually an international panel, which you'll hear about as well, that is working on this. Initially through the academic side and then working out through the other stakeholders. And again, the third initiative is to work with the pediatric device working group, initially on a quite specific project, but we feel it's also important to bring in initiatives like this and understand that the collaboratory can be a place where specific issues like this are addressed. So they are specifically looking at the indications for subcutaneous ICDs in the pediatric population and helping to work that problem. So we look forward to inviting in other initiatives of interest within the EP community in this way. And so, you know, again, the mission statement, as I mentioned before, is really the key. Thank you and stay tuned for the future of this. And I'll turn it over to Dr. Jared Bunch, who will share more about the AHRQ project. Thanks, Pete. And while Jared is coming up to the podium, I just want to encourage you to submit any questions you might have. One just popped up, which is great. I hope there's 10 more when Jared's done. So please submit your questions. We're looking forward to a discussion after this. So thanks. Take it away, Jared. Thank you. Thanks for coming this morning. Thank you for the opportunity to work with all of you. It's been, I always enjoy the opportunity to learn from others and be in a room full of people that inspire me and motivate me. And I want to talk about our role in developing new atrial fibrillation endpoints. And I want to share some examples of how we're thinking through it more than, say, text of our scope in general and to understand sort of how we're approaching it. Nope, that's not what I wanted to do. Okay, these are disclosures of mine. So we consider that we need first the standardized definition. We need to establish clear and uniform definitions of successful atrial fibrillation endpoints. And as everybody knows in this room, they've been quite diverse. And we lose an opportunity to really compare things, understand things, and understand how the endpoints correlate with other outcomes without clear definitions. So for example, we've used arrhythmia-free survival, and the historic and traditional endpoint is freedom from atrial fibrillation from 30 seconds. And that's worked very well for us, but we've also recognized for two decades the significant limitations. So as we engage this project, we want to think about alternative opportunities. And we have new technologies that offer more insight into the patient day-to-day, such as atrial fibrillation burden. And part of this is, and some of the challenges, is how do we measure this? And there was a clinical consensus document recently from the ESC and ERA, and they talked about the need to accurately measure AF burden. And of course, the most ideal way to do this was with an implantable monitor. And when you introduce an implantable monitor into a trial, you lose 50% of your trial enrollees right away. They just don't want it. And so it is optimal, but it has limitations. We can use near-continuous monitoring, medical grade, and for a period of 28 days. And they can provide a reasonable and feasible assessment of atrial fibrillation burden. But we also understand that as we start to interrupt our sampling period, we overestimate how arrhythmia frees survival. And the measurement of atrial fibrillation depends completely on the monitoring duration, and also the compliance of the non-continuous monitoring we're using. In patients with known atrial fibrillation, validated wearable measures are now becoming commonly used. Approximately half the people in the US have smartphones, smart capacity to detect atrial fibrillation. And can these be used in a compliant manner over time? Compliance for three times a day sampling is about 80% the first month, and by six months, it's about 10%. And so we have this big issue of compliance over time with even wearable forms. But it conveys interesting information. As you can see here, and it's a little bit busy, but these are multiple trials that have looked at the role of atrial fibrillation and how it correlates with burden. You can see the burdens, as I mentioned initially, are completely different on the right side. But all of them convey unique and important information regarding risk of stroke, fatal stroke, and death. And so you can put that burden in a schematic pattern where you segregate the time you're in atrial fibrillation, and you add to that disease burden in the CHADS VASc score. And then use that to create actionable thresholds for treatment, whether that's rhythm control or anticoagulation. And then we can use the same paradox to power and formulate our trial design to make sure that we achieve the endpoints we want, we're adequately powered, and we can understand if we do have a meaningful difference. As you can see with atrial fibrillation burden, and this is nice work by Derek Chu, it helps if we're looking at trials for mortality, for resource utilization, for all-cause hospitalization, CV hospitalization, ischemic stroke. And so on the surface, it seems like a great endpoint, we need to move that way. But when you look in the community, it's not that simple. And the distribution in the community and patients with implantable devices at the University of Utah, people don't have a continuous burden in the community, they tend to be on the extremes of low burden and high burden, they display a low burden phenotype and a high burden phenotype. So how do you take this data and apply it to a scheme where you're assuming continuous AF burden, and it could be a challenge. And if you undersample on low frequency atrial fibrillation, you can game the system. If you want to show your device is more effective, you want to enroll people with very low burden. And they're going to do better almost no matter what you do. Or if you want to make a meaningful difference, if you're a mechanistic person, you want to enroll people on the other side where most of the adverse events occur and most of the challenges occur. So some of the challenges, how do we assess AF fibrillation at baseline before ablation? Rhythm control has been initiated and all of a sudden the burden before enrollment is zero and how do you improve upon that? And is it realistic to allow somebody to be in atrial fibrillation if they're symptomatic to create a burden and then compare it over time? And what type of assessment prior to ablation is needed? And as AF fibrillation is performed early in the disease process, burden changes may be modest and the baseline may not be helpful at all. And so should we use a fixed burden, say a goal of less than 2%? Or if very early, should it be we go back to that 30 seconds where we want to define something that's so modest because there's very little atrial fibrillation? And we also have to understand what matters to the patient. These are quality of life scores in patients with atrial fibrillation, post-MIs, and in control. And you can see patients with atrial fibrillation report symptoms worse than those that have had a myocardial infarction. And when we look at that goal of 30 seconds, in fact, our patients, very few of them care much about the burden they're having if it's less than 30 seconds. Some say, I'm okay and it's successful if I've had atrial fibrillation multiple times a day or 30 to 45 minutes as long as I feel better. And so we have to correlate what the patient cares about with what we're actually studying. This is another way, looking at the frequency of episodes, once a year versus two to four times a year versus once a month. And you can see there's a group of people that even if they have four to five times a week of atrial fibrillation, they still feel that the procedure impacted them in a meaningful way. And so how do we bring into the patients early on to find out what's important to them and integrate them into our research trial designs and our therapy assessments is really critical. And there was a late breaker I commented on yesterday that had no patient input. The goal was pulmonary vein isolation with adenosine, which has no relevance to patients at all. And that was their safety end point, or that was their efficacy end point. And I think it's a missed opportunity to help the people that we have the opportunity to serve. So what about secondary end points that include, could be freedom from an episode of atrial fibrillation over 30 seconds. So if we abandon this, we actually still need to include it because then we have the opportunity to compare with historical understanding and historical trials. And so we still have to look back on the past so we don't repeat failures. And we also can continue to grow on what's already been done. So I don't think we want to move in such a way that we miss the opportunity to compare with what's been done. So how do we optimize trial designs to maintain safety and efficacy as it sees the therapy while accelerating innovation? So we need to be pragmatic at the same time that we try to understand the disease process better and our treatment better. We can personalize follow-up duration. So a traditional end point is one year post-ablation, 90 days with a blanking period. But there's an alternative opportunity when we know what the therapy is, like a radial frequency catheter, and maybe the handle's different or something like that. We can truncate that to six months, and then we can use long-term registries to look for long-term events. This is an example of thermal trials showing ablation versus drug therapy, cryo-balloon. This is the ADVENT trial showing cryo-balloon. The cryo-balloon does well, and we gain little information going beyond six months. So if Boston comes along and has their Polar X trial, perhaps six months is long enough for them, and then make sure that we have a registry to understand rare events. Now for pulse-filled ablation, I think it's a little bit different. We have similar efficacy in the ADVENT trial, low strokes, but when we followed long-term, we started to note new complications. One of the challenges with pulse-filled ablation is it's apple to oranges with each device, and they probably need a randomized trial design and longer follow-up. So I want to conclude with this. So if we could understand therapy of signs, if we want to expand traditional endpoints, there's opportunities to look at covert and overt stroke. We can do cognitive testing compared to just stroke with disability for quality of life. We can use more disease-specific outcomes. We can include outcomes in all of our efficacy trials because that brings in to the patient. We can look at hospitalization rates, which we've done traditionally, but we can also and more importantly do comprehensive tracking of healthcare utilization. You know, PFA cost a ton, and that margin of profit to the hospital is shrinking, and it impacts our ability to care for patients. Pharmacology needs, we can not only look at changes, but we can assess the duration and necessity of anticoagulation therapy, like the Oceans trial will do this year. And again, patient satisfaction I think is critical. We often lose the mark if we don't include our patients in our trials and understand what really is impactful and meaningful to them. Thank you very much. Thanks, Jared. We're going to ask Dr. Vilcek to come up and conclude our presentations for today. He's going to give us the HRS perspective on the EP Collaboratory. So thanks so much for being here, Ken, and for everyone else, please continue to submit your questions. Looking forward to discussion. Thanks, Emily. So, great presentations on this important initiative for the EP Collaboratory. I'm here to provide the perspective from an HRS organizational standpoint. We're all part of HRS, but from the workings of the organization, how does the EP Collaboratory fit in? I'd like to go back to a little history, because I was involved in the initial effort to create an EP Collaboratory within HRS, and really happy to see that this has all evolved so nicely. Thanks to the leadership of Dr. Wong and Dr. Weiss here. We did a membership survey in 2020 to assess member perceptions of barriers to successful heart rhythm research, and we published this figure in the EP Collaboratory white paper from 2022 in heart rhythm. 300 participants completed the survey, and a good proportion were outside of the United States. They identified the need for a collaborative research platform to address several challenges, including identifying funding sources, identifying collaborators, connecting with industry, help with FDA submissions, creating research dialogues, access to clinical trial databases, basic science collaborations, connecting with professional societies and others. So I'll also talk to you about other efforts within the society that are aiming to facilitate collaborative research and are complementary, I think, to the efforts of the EP Collaboratory under the leadership of MDIC and Stanford Biodesign. So I'll call the original go at the EP Collaboratory, EP Collaboratory 1.0, which was outlined in this manuscript that I mentioned to address increasing costs and complexity with research and competing demands, regulatory requirements, and difficulties with study implementation. A lot of the themes that you've already heard from the previous speakers, ideally the research would be focused on important unmet needs in clinical arrhythmia medicine or scientific knowledge gaps. So we proposed something involving clinical, translational, and basic science communities, industry, regulatory agencies, patient representatives, and funding agencies. And so I'd like to make a few contrasts here between some of these different entities to help you understand the differences and also mention, lastly, the HRS Research Network, which will be presented at the 945 session this morning. So I'd say that the EP Collaboratory first attempt, or EP Collaboratory 1.0, was aiming to do a lot of the things that the EP Collaboratory, we call it 2.0, and the HRS Research Network are now doing. But in 2022, the Board of Trustees determined that HRS was not the appropriate convener for this. And now, fortunately, we have the leadership for the EP Collaboratory 2.0, and HRS is very happy to be involved in a supportive way for the EP Collaboratory 2.0 and see the role of the convener to these entities, the Stanford Center for Arrhythmia Research, Bayer Center for Biodesign, and the Medical Device Innovation Consortium. And then I'd also like to contrast the scientific documents, who is doing scientific documents. The Academic Research Consortium, under the leadership of Dr. Bunch, you've heard, is identifying important issues for atrial fibrillation endpoints. The HRS, our society also has a Scientific Documents Committee that could also write a document like this, and so I think there's an agreement to share these different roles in putting out scientific documents, as I'll elaborate on shortly. And then the HRS Research Network, as opposed to what you've heard about the current EP Collaboratory, with a focus on really early studies and getting these technologies to the market, streamlining FDA approval, and involving all the stakeholders that are key to this process, the HRS Research Network is really focused on broad, collaborative, basic science, translational, and clinical research, not necessarily very early adoption of very early technologies. So again, we recognize this importance, and it's expected that EFS will frequently be sponsored by these smaller companies, as larger companies already have established pathways. And the development of these high-risk technologies by small companies is acknowledged to lead to acquisitions by larger companies and feed into the ecosystem. So here are some entities within HRS that I think will interact with the EP Collaboratory. There's the HRS Research Committee, the HRS Scientific Documents Committee, HRS Health Policy and Regulatory Affairs Committee, and then all HRS committees ultimately report to the HRS President, CEO, and the Board of Trustees, and we've worked out communication via HRS Committee liaisons and HRS staff. So from our perspective, there are some major advances that I think could be used to model what else we can do in the research network and other spaces. One of them is this master contract agreement that we've been working on with the EP Collaboratory to allow institutions to approve these early feasibility studies in an early and efficient manner perhaps with slight modifications or whatever modifications are needed, but this template is a very important approach to not having to start at the beginning every single time. I'll comment on the scientific documents because I think this is an interesting give and take between the ARC here. So if the ARC were not writing this document, it probably would have been managed by the HRS Scientific Documents Committee, but interestingly, if you think about the experts in the field, ultimately the people writing the ARC document say if it was under the purview of the Scientific Documents Committee, it would probably have been the same because these are the experts in the field and are HRS members. So in this situation, it's just interesting how it worked out where the ARC took responsibility for atrial fibrillation endpoints and the HRS Scientific Documents Committee is focusing on a document on ventricular tachycardia therapies, but then as a connection to all this, we plan to ultimately review and endorse the scientific document from the ARC. The research network and EP Collaboratory 2.0 contrast in these ways, as I mentioned with the focus on EFS versus the broad approaches to collaborative research. So I'll just make a few comments in closing about the HRS research network. So here we're interested in a cost-effective and feasible approach that can be facilitated by HRS, where HRS can provide the infrastructure and the Board of Trustees can approve it. In particular, I think registries to address risk stratification for sudden cardiac arrest are of interest. Registries for cardiac physiologic pacing, comparing left bundle branch area pacing, his bundle pacing, and biventricular pacing are of interest. Applications of CMR and AIECG are also of interest. And I think these, in general, will give us long-term outcomes. Dr. Bunch made reference to the idea of the need for outcomes beyond six months for, say, cryo-balloon or PFA. And I think we'll want to know what are these outcomes. For example, for PFA, you know, you could argue that there may be, like, long-term atrial flutters or something like that from modification of the tissue, and you just wouldn't know that from really a short-term follow-up. So we're interested in all these things, registries, basic science collaborations, and biorepositories with incorporation of AI methodologies. So then the scope will be to facilitate the full spectrum of heart rhythm research, provide the infrastructure, we're going to, I think, offer a matchmaker paradigm to connect electrophysiologists with each other and industry, facilitate access to regulatory agencies and payers, communicate research funding opportunities to the membership, provide career development opportunities and opportunities for clinical trial leadership with gender diversity, and then support the mission of the Heart Rhythm Society overall. Here are the milestones where, in year one, we're proposing development of the operational framework, the brand, the marketing assets, establishment of inaugural idea exchange, establishment of operational structure, and then in year two, launch of the program, outreach initiatives, development of educational content strategies for researchers, and then in year three, exploring the development of a data collection platform. In conclusion, clearly the HRS, as an organization, supports the EP Collaboratory, and I'm grateful to all the efforts of MDIC and Stanford as conveners for this EP Collaboratory. We believe it will have a very positive impact for heart rhythm care, for bringing new technologies to the market, with an efficient process for FDA approval and planning for CMS reimbursement. And then we also believe that integrations with liaisons and chairs are key, and future planning of scientific documents will help avoid overlap, and that's it. Thanks. Thanks, Ken. That was great. We were on time, which is maybe the greatest innovation in HRS history. We have one question. I don't know, Paul, if you wanted to ask anything, or I thought we could reach out to some of our FDA colleagues in the audience, or Dr. Van Hare, who we see here, who's been really engaged in EP Collaboratory. And we've heard a lot this morning about the Early Visibility Studies Program, and I wonder if, maybe it's obvious to everybody, but I wonder if you could share a perspective from the FDA about why it's so important and why the good work that's been done in EFS and other therapeutic areas, why it feels like an important time to bring that to the EP ecosystem, and how the EP Collaboratory might participate in that. I guess, thanks. So I'm, as an FDA employee, I'm actually not allowed to speak at national meetings yet, but I think I am allowed to, you know, comment as long as no one tells anyone. So first, I guess your question is about the collaborative community question and why it's important, right? So, you know, FDA is, there are rules around who we're allowed to listen to, okay? So it's called the FACA, the Federal Advisory Committee Act, and so there's guardrails around who we're allowed to take advice from, okay? To sort of limit the opportunity for people to sort of, you know, influence the decisions that the agency makes. And so this is where advisory committees come in, right, which are very tightly regulated in terms of conflicts of interest. We have special government employees and things like that. Collaborative communities are designed to be another route for FDA to get input from the larger community. And they're specifically, and CDRH, it's actually a CDRH, you know, thing, and it's designed to allow multiple stakeholders to come together to, you know, work on, you know, these kinds of problems. Collaborative communities are not led by FDA, but they're recognized if a collaborative community is established and then invites FDA to join, we will do that, and if we're happy with the charter, we will put it up on the website. So that's sort of where that comes from. In terms of EFS, you know, why do we care about that? So one of, and this is a very U.S.-centric, you know, discussion, but, you know, we're required to make sure that when we approve a device that the clinical data that's used is applicable to the U.S. population, and depending on what the device is and what the application is, there's various, you know, things we might care about. Traditionally, clinical trials will, you know, involve at least 50% U.S., you know, subjects so that we can actually have some, you know, some, you know, confidence that the results are applicable to the U.S. population. In terms of things like, you know, gender and ethnicity and age and BMI and whatever the other important sort of factors are. So if you sort of think about it, the earlier you start to collect U.S. data, the earlier you'll have clinical data that we'll have confidence about, right? Also just from an operational standpoint, you know, if you sort of, devices are fundamentally different than drugs, right? Drugs don't change. Devices change. But also, you know, drugs don't really care who's prescribing it, but devices care about who's putting it in, right? You can't really separate the operator from the device. And so the outcomes are partly based on the skill set of the operators. And so we care about having U.S. data because that's what we're sort of approving for. And so the earlier a company gets a group of experienced implanters in the U.S. involved in their clinical trials, the better from our point of view. So did I answer your question? Absolutely. Yeah. That was fantastic. Thank you. All right. Right. Yeah. Actually, George and Emily, and I guess I'm a little shy about throwing this out into the universe, but I think it's a good opportunity to, and it'd be interesting to have people's thoughts about this. You know, part of the beginning of this initiative for early feasibility studies is the recognition of some of the lack of availability of these technologies to U.S. patients early on. We all know the story of the Taver valve, for instance, where we're the 42nd country in the world to have access to this for our patients after all the development. And that's not an uncommon story where some of the engineering work and even VC investment and other things that go on in the U.S. and then things move overseas. So here you go. All right. So do you think there may be a opportunity, in a sense, a silver lining to some of the current environment to actually emphasize the importance of bringing that stuff back to the United States and actually make use of that change in the milieu to break down some of the barriers that have existed from some of our regulatory partners in particular? You know, CMS is always a bit of a mystery, and of course their ability to be present at this sort of forum has always been limited, you know, much, much more so. But do you think there's an opportunity here actually to move some things in our direction from that perspective? So, well, I'm obviously not going to comment on a lot of the current clinical changes, but just to sort of maybe echo what Rob Califf said yesterday and, you know, the idea that, you know, when things are changing dramatically, there are opportunities to sort of rethink things. You know, it's important to recognize that, you know, most of what FDA does is just applying the regulations that Congress passes, right? So, absent new regulations, we're going to apply the regulations. But there is, you know, FDA guidance documents actually define how FDA thinks about how we apply those regulations, and, you know, I suppose that might change. I think the EFS program is a great example, right? Because normally we would require, you know, a complete set of preclinical data before, you know, considering approving an IDE trial of whatever type. And so this is a recognition that we don't necessarily need all of the preclinical data in place in order to start clinical trials. The whole concept of EFS is that you reach a point where you can't get any more information from animal data. You have to start to iterate your device in humans. And so there's sort of a recognition that we can be more efficient in terms of approving sort of early sort of things. But then when you move to a larger patient population, then because you're multiplying the number of patients, you're multiplying the amount of risk, and so then at that point we may ask for additional, you know, additional data. So the idea was to try to streamline getting devices to humans a little bit earlier in the U.S. That's sort of where it came from. And some of that, I think, is just sort of interpreting the regulations that were required to follow. And, you know, this stuff keeps changing. So perhaps it'll change again. I don't know. Thanks. We have a lovely question. Actually, many lovely questions. But I think there's a nice one here to sort of tie all this together. And I wonder maybe if everybody could comment on this, including you, Dr. Wong. The question is, can you talk a little bit about how a small business or a startup would start engaging with the EP Collaboratory? I think this is sort of the whole point of why we're here. So I'd love to hear perspective from the panel on that question. Thank you. Thank you for that question. It's a terrific question. We're here to do that. So the EP Collaboratory, under the EFS-facing part of it, wants industry, large and small, to reach out to us. We're here to facilitate. Ultimately, MDIC will do the pairing, in terms of people interested, if the industry has a, you know, wants to proceed. Clearly, we want them to reach out to both FDA directly, and we can facilitate that, too. So, yes, please, you know, contact us. I'll emphasize again, one of the points that we want to make is that we think there's great benefit, and in terms of for large and small industry, to facilitate the whole process to a pivotal ID and final approval. So entering the EFS early, really, we think, will facilitate the overall process. And so we really want to engage people as early as possible, and as frequently as possible. And, again, I can't tell you how, you know, committed the FDA is to making this a fruitful process for industry. Jared, what do you think, from the AF endpoint's perspective, I mean, is there a role for industry to participate in that, or how can they contribute to that effort? Yeah, that's a great question, and I put that out in my commentary yesterday. I think, most of the time, what I've found is industry will follow the path of least resistance, and so the burden falls more on our shoulders to create guidelines that provide us the information we need to succeed, and really help patients. But I think industry has to understand that they have a role, and also the general health of people. And there's an opportunity to, in every trial, Doug Packer would always say, we need to study this catheter so it gets approved. But that doesn't stop us from asking an interesting question along the way. In the commentary yesterday, it was a PFA catheter, and they mapped with the PFA catheter where the electrodes just really aren't in a good spot to map, and the company that was doing the trial has a wonderful catheter, and we have no idea what thresholds of measurements to look at the heart after PFA. And they missed an opportunity that they could say, well, I'm going to study, I have a good catheter, I'm going to provide the community with thresholds to remap that may guide dosing. So I think there's always that opportunity, and I think the other, where we can begin to engage industry early and say, what are the meaningful, interesting questions? These are, we understand your spot, and what you need to do, you have shareholders and things like that, but here's some interesting questions that won't necessarily hurt your catheter, but will help us in the community. I do think there's some opportunity for Synergy to start asking interesting questions along the way and engage industry, but it is a definite partnership, and I'd like to see it be a little bit more collaborative. I think we've been given the hook here with the lights, but no, okay, well, anyway, it is top of the hour. So I'm so glad to have seen this full room. There are a bunch of questions that didn't get answered. I suspect many of the panel members will be willing to hang around and answer questions. So thank you so much, and again, thanks to Dr. Van Haer for being voluntary to answer some questions, and thanks to everybody for participation. We hope that you'll engage with the EPC, EPC, that's what we're calling it. Thank you very much. Thank you.

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atrial fibrillation

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