My name is Donato Mancini. I'm a reporter at the Financial Times. I write about health and pharmaceuticals. We're in here today for this event titled Decentralized Clinical Trials in Focus: Overcoming Challenges to Drive Economic Value in Clinical Development. It's an event that we're holding in partnership with ICON. We have a star-studded panel that is going to discuss a couple of the hot issues in the sector with us in just a moment. But before I do so, I would like to remind you that you can ask questions. We love your questions, and we'll be sure to save time at the end of the event to ask some of our panelists. You're more than welcome to share any thoughts that you might have on the content of the discussion on Twitter, using, well, X, formerly known as Twitter, using the hashtag #FTHealth. And if you would like to do that, you can head over to the community chat to have discussions with other attendees. Again, we want your questions. We love your questions. It keeps our panelists engaged and then make sure that, you know, we can, we can help you, we can help answer any questions you might have. I'm going to ask my panelists to introduce themselves very briefly, and then we'll move on to the discussion. So, Angela, would you like to start? Thanks, Donato, and thanks for having me on. I'm Angela May, Head of DCT Strategy and Implementation at Bayer in Clinical Operations. My team and I work directly with project teams to develop and implement their DCT strategy, as well as helping to develop the broader organizational capability and infrastructure for DCT. Thank you so much. Jane? Hi, good afternoon, everybody. Thank you very much for having me here today. So my name is Jane Twitchen. I head a group at Biogen called the Clinical Trial Accelerator Unit, and we have a number of sub-functions within that group, spanning everything from feasibility to clinical trial diversity and including DCT along the way. Very similar, similarly to my colleague at Bayer, we work across the portfolio, defining our strategies, selecting vendors, and ensuring that we do everything possible to be patient-centric in our approach to DCT. Thank you. Thank you so much. And lastly, Harpreet from our partner, ICON. Thank you, Donato. So I am Harpreet Gill. I head up the Decentralized Clinical Trials Solutions team here at ICON. And, not dissimilar to, my panel members, I do have, responsibility for driving DCT strategy and, operational delivery, at ICON. And, as the partner for this session, I am going to tee up, some of the questions. So if you wouldn't mind popping up the slides, I'll just run through some of the topics that we want to discuss today. So initially, I think what we want to talk about is our recent experience of decentralized clinical trials and where we're seeing some of the greatest benefits, and how these are influencing the decisions around implementing decentralized components. And then, there are challenges. So we do want to discuss some of the technical and operational challenges that we see and how perhaps they can be real significant barriers to adoption, how perhaps we can overcome some of those barriers. And then we can't forget regulatory guidance. It's really important that we have enough clarity and confidence to proceed with DCTs, particularly using novel methodologies. So do we have enough clarity? What are the thoughts on the regulatory guidance we have in place to date? Mm-hmm. And then, we do want to look at some of the fiscal impacts of decentralized clinical trials and understand what some of the underlying evidence might be out there in terms of what the outcomes are compared to traditional trials. And then finally, let's see if we can talk about some of the ways that we can measure the economic value of these centralized trials and see if there are any emerging trends in that area. So, that's it from me to tee up. I'm going to hand over to Donato, and I see we have our other panel member on camera now, so hopefully she can join us. Thank you so much. Hi, Stephanie. You made it. I have. Hi, everyone. It's wonderful to have you here. So we just started with the introduction, so you came in at the right time. Would you like to briefly introduce yourself, and then we'll get started with the conversation? Hi, everyone. We've had some last-minute technical challenges, so we're talking about decentralized clinical trials and technology, so very topical issues that I've been experiencing. I'm Stephanie Manson Brown. I'm Head of Clinical Development and Scientific Innovation and Vice President at R&D for Allergan Aesthetics at AbbVie, and I'm delighted to be part of the discussion today. We are so happy you could join us. There was, there was a risk. We thought for a second that you might not be able to, but we're very happy you're here. Let's. I want to remind our audience that we love your questions. There should be a space on the right-hand side of your screen to submit these questions, which will then make it to me, and I'll be sure to put them to our panelists. So please, please, please ask away. So let's start the conversation with. Obviously, decentralized clinical trials are incredibly importantly, hugely valuable for certain parts of the industry, also for patients. They made a huge kind of exploit during the pandemic for obvious reasons. But, I would like to ask my panelists, what have your experiences of clinical DCTs been like in the past year and in the past few years, and where have you seen kind of the pros of DCTs emerging, and how are you holding these in mind when you make decisions in the clinical space or the regulatory space or whatever space? Why don't we start with Angela, and then we'll move on. It's funny, actually, Donato, that you mentioned the pandemic, because I think there's really two camps there. I think some people really think that it, it held us back as opposed to, to pushing us forward, and I think, myself, I think it was a double-edged sword. But, what we've, we've really seen now is, is rather than the whole, "Help, we need business continuity in crazy times," to actually, we've seen that, that life can be more flexible. Mm-hmm. So why, why not clinical trials as well? So, you know, with the teams that we're working with, we've seen a lot of really good engagement, people really wanting to change things, to modernize things, 'cause recognizing that, you know, we can't stand still with our conduct, and that it really needs to get a bit better. Mm-hmm. So we've seen a lot of engagement from our teams, which is what we've really needed to explore approaches in studies. Yeah, we've had some quite... Well, you know, we're still on the journey, but we've had some interesting findings so far. Well, could you give us an example? Yeah. I mean, actually, all of our studies are phase 3, so it's a bit of a slow burn. But two of our studies, we've really managed to pull out some metrics, which, you know, anyone in the space will know that we're obsessed with metrics in clinical trials, but pulling them out for DCT was a bit easier said than done. Mm-hmm. But we've managed to get some preliminary metrics out of some of our studies, and we've seen that, you know, maybe some of these promises for, you know, supporting recruitment and retention and diversity, actually, maybe that's true. So we're seeing some early signals that really might be the case, which is really exciting. That's interesting insight. Jane, what about you? What's your experience been like? Yeah. So we're similar to Angela, that we've had some exposure to DCT in a number of trials now, and we've kind of got two extremes. So we've had real success on some non-interventional natural history trials that we've done in a completely diverse fashion. So we've done a collaboration with Apple called the Intuition Study, where we've used the Apple Watch, iPhone, et cetera, for collecting some data about patients' cognition, brain changes as we go about our daily lives. So that's been fascinating and really exciting. The data there has been really useful. We've also done a completely decentralized childhood epilepsy study, which was very much about putting the patient first and really minimizing the impact on these incredibly ill patients' lives. More often than not, though, we're looking at small elements of the protocol, so is there a part of the study that we can deliver in a decentralized fashion? One study that springs to mind that we started recently is for a rare genetic condition, and the patients that we're bringing into the trial aren't. They're not even patients, they're pre-symptomatic gene carriers at the time the study starts. So we wanted to make that run-in period as non-impactful and as hands-off as possible, and give those patients a huge amount of choice about how and where they communicate with the medical team who will take them through the clinical trial. So is that in the home? Is it in a sub clinic, which is closer to their house than the main investigator site? Is it in a corner pharmacy for their blood draws? So really, for that long-term run-in and giving a lot of patient choice. So yeah, we're beginning along this journey. We've got some good experience. We're still learning along the way. I think Angela mentioned diversity, and I think that's one of the drivers that we've seen, particularly on the studies that we're now having to or want to have FDA diversity plans in place and really attract all sorts of different people into our study cohorts. I think giving, excuse me, more choice is, really the path forward. So that's, that's definitely an area that we're continuing to explore. Just to get some input from you on this, because it was really interesting: Whose idea was it to get the pre-symptomatic to sort of use DCTs for pre-symptomatic patients? Was it physicians? Was it the patients themselves? Was it you? Who drove that decision? So, all of the above. I mean, it was an unusual study for us to really start so early on in the process, and we were very. We thought that a sort of a flexible protocol with decentralization was the way to go, but we were also- Right. very wary that these patients are dealing with a genetic diagnosis they might not be aware of, and there was an ethical responsibility as well. So we wanted to make sure that we got the support right, and that might not be right for every patient. Some patients might want to carry on living their life as normal- Others might have a real thirst for knowledge. So the flexibility that DCT gives us was really important, and we discussed that with a genetic ethicist, as well as investigator sites and patients, to get the full remit of feedback. Fascinating. Stephanie, I see you're back online, and I'm very happy that that's the case. The question that we were discussing is: What have been your experiences of DCTs? What are the benefits that have driven your decision to use them, and when you make decisions in this space? What has your experience been? So I'm very hopeful that my connection will maintain. So my apologies to my other members on the panel. I really hope that I'm not causing any disruption to any of the discussions. I've been... I'm fortunate I did manage to hear Angela and Jane's input, so, you know, some really great examples and also some, you know, I think just generally the way that we're approaching things is relatively similar. We've had a lot of learnings along the way, like many people, and we'd already been implementing certain measures with regards to what would come under the umbrella term of decentralized clinical trials.... So before the pandemic, this was locked before lockdown, but obviously, that was an impetus for everyone across the industry, really, to look at enhancing those options. So just to bring in an example, some of the learnings that we've had is actually by centralizing a lot of our initiatives around decentralized clinical trials, and so large company with multiple studies running in parallel, obviously. And this is something that we've made that realization, that by bringing a dedicated team in for decentralized clinical trials and from an AbbVie perspective, has enabled that identification of the commonalities. Because sometimes where ad hoc basis, or you get clinical study teams addressing it as per the needs as it pertains to their own clinical trials. But of course, and that, that needs to be done when you are thinking about patient care, and obviously the needs as it, as it relates to that particular condition or the compound or asset that you're studying. But there are some commonalities, especially when we're talking about patient reimbursement and, and trial support. So just to share some, some of our learnings, we have, 40 trials happening on the therapeutic side. We've got multiple other trials in the aesthetics side of things. And this is where they really identified some commonalities and identical challenges that the teams were facing and looked at where they could implement certain issues with regards to the management of third-party vendors, and making sure that we had a consistent way of reimbursing our patients, and ultimately have a more efficient way of solving some of the problems that crop up, rather than everybody having to handle and deal with them themselves. And so this is certainly, from a more widespread perspective, how we're addressing things. I head up clinical development for aesthetics and aesthetic medicine, and this is an area where we've seen some really great opportunities with respect to enabling more enhanced efficacy measure collection. I'm looking at mobile image capture, for example. That's something that previously patients were having to go into, and subjects were having to sites for regular image capture to enable us to be able to identify the evolution of the outcomes there. But we've been working on creating tools that enable the patient to be able to capture that at home and putting in the robust methodology to be able to correlate that to existing photo numeric scales that we use. That's fascinating, Stephanie. So are you creating specific software for this? Like, for example, apps that patients can put on their phones, or how does it work? Absolutely. So it is software, and it's something that we're looking at applying it to all different types of Androids. And just to kind of give some context, with imaging, regardless of which field you're talking about, the positioning and the lighting of the patients, and the distance from the camera, the angle, et cetera, that all very much plays with regards to the actual image and the results that you're then capturing. So this is a really important measure to be able to standardize it, to ensure that you've got that consistency. And so absolutely, to that point, and developing the software to enable that consistency and standardization, 'cause ultimately, we need to demonstrate to the regulators that we put that robust and methodology behind it so that we can, you know, provide it as an alternative currently. But then ultimately, the future will be looking at bringing that in as then the superseding some of the endpoints that we're using currently. Thank you. Harpreet, what- Yeah. What have your experiences been like? Yeah. So, not dissimilar to my colleagues on the panel. I think initially, you know, we obviously saw some drive from the pandemic. I think certainly what we saw at ICON was a little bit of a pullback from going down the decentralized route, and there's a level of comfort in going down a familiar route, a traditional route. So, a little bit of a pullback, but I think now, with the guidance from the FDA and the EMA around diversity and also making trials more available, easier for patients to participate in from the EMA, I think that's really driving the debate further and pushing us down a decentralized and more sort of broad thinking route as well. Decentralized, I think, doesn't just mean technology. It's also thinking about some of the other services that could be provided for patients, such as community clinics, using the pharmacy, home health, using other services, concierge services, et cetera, just to engage them in the trial and ensure they stay up to date with the protocol, but also supported through the clinical trial and understand the process as well. I think education's a really important piece for the patients. I think we need to be better at educating patients around exactly what it means to be in a more decentralized clinical trial. I think some. We did have some feedback that some patients thought it would be more complex, and that's hopefully not going to be the case in most DCTs. So we've seen a range of things, and certainly from our sort of practical experience in terms of delivering some clinical trials for sponsors- -we've definitely seen some real benefits around diversity. I think that is going to be a key part, a key asset of DCTs that you wouldn't see in a traditional trial. And it goes back to the fact that these studies are more accessible. You can generally, if you're doing things more in your local community, not having to go to a specialized site for all your visits as frequently, that your ability to engage in a clinical trial becomes a lot easier, and you get that optionality as well. So I think we've definitely seen that. We had one study where not only did we see a sort of 50%, non-Caucasian population, but we also saw 20% of those come from a rural location. So that speaks to, again, diversity, not just from an ethnicity perspective, but also from socioeconomic factors. Yeah. Yeah. That's fascinating. As a reminder to our audience, we want your questions, and we want them now. I see a couple are coming in, but we want to have a plethora to choose from. So let's move on to the following point. So, I think Jane earlier was saying that there was a partnership with Apple? And then Stephanie was talking about their own kind of like software developments, let's call them that, to kind of follow up on their patients. So what are the challenges that you have encountered in terms of technology and operations in conducting DCTs? And are these teething problems that can be addressed easily, or are they significant, are these structural issues? Why don't we start with Jane, who can hopefully talk about the partnership with Apple as well? I could do my best to talk a little bit about that. Technology from a kind of mobile infrastructure wasn't as complicated as we expected it to be. I think, you know, if you-- I think there's a famous image, isn't there, of a mobile phone at a concert, and sort of 20 years ago, there's 3 in the crowd, and now absolutely everybody has a, has a mobile phone. And along with that comes the infrastructure to deal with that. So, you know, looking at Biogen's country footprint, so where we usually take studies and where there's a really strong mobile infrastructure, if you know, in that particular example, we haven't had huge technology challenges. Where we've had more, I'd say, challenges or considerations, is on what we sort of refer to as the site burden. So what are we gonna ask the site to do? How are they going to do it? How are they gonna be trained? Do they need access to another portal? I think, you know, sites are really fed up with having lots of different logins to lots of different systems and being knowing their patients via data rather than patients as individuals. So sort of working through those challenges have been the ones which have been more impactful. Another point, which is maybe moving away from the tech, but it just kind of dovetailed quite nicely with some of the comments we've had about diversity that Harpreet and Angela have also shared. I also wanted to raise kind of the operational piece there, 'cause we've got the tech part of DCT, which is absolutely critical, and that's maybe the exciting bit. But then, as Harpreet and Angela said, we've also got the how do we make it easier for our patients in terms of, is someone coming to them? Are they going to a clinic? Where are they receiving our care? We've, funnily enough, have had more operational challenges with that kind of end of things than we have with the tech. Really simple things, but they're really meaningful to patients. Simple things like, if we see a nurse one month, we'd like to see the same nurse the next month. If I'm inviting someone into my home, I'd like it to be a face I'm familiar with. Going a step further, I'd like it to be a person that looks like me. So if I've not got white skin, I'd prefer my nurse not to have white skin. So if an element of diversity is about making this easy for the patient, making the patient comfortable, I think those parts are really important, and maybe vendors aren't necessarily set up to think about all of those parts yet. And then also some sort of logistical challenges that went with that, that often we've got people coming into the homes and doing blood draws, and then the bloods have to be sent off for sampling, and that has to happen with dry ice and a courier. So you've got three pieces there coming together. You've got the nurse, you've got the equipment, you've got the courier, and it's just, as sort of Stephanie mentioned, having a team of experts who understand that infrastructure, who understand that model, can put that model together for every study without having to invent the wheel from a kind of logistical oversight piece. That's been really critical. So yep, I'd be fibbing if I said there weren't tech teething problems, but I really think they were more teething problems, and it's the sort of same old operational things that have some level of complexity, too, that you've got to navigate. Thank you so much. Angela? Yeah, I think I would largely agree with Jane, actually. When we've had teething problems, I guess, in specific countries, you know, for example, importing, you know, some... You find out late in the day that there's some weird reason why you can't import this specific device into this specific country, so you have to work around that. And maybe the vendor or vendors that you're using to provide that equipment or tech don't have specific experience in that country, so then you need to deploy your local team with their knowledge to help you. So we've seen things like that. But I think our tech issues have been more with the build, so actually building the platform or the, you know, the portal or app or whatever- in the first place. In the challenges in making sure that it is fit for purpose, that it doesn't, you know, land a whole bunch of burden on your sites and your patients, as Jane was saying. So, you know, yeah, we might think it's brilliant, and it does exactly what we want it to do, but actually, from a site point of view, is it very friendly? So it's been more around that, I suppose, and yeah, making sure that that build is fit for purpose for the study, but also for the users. And in particular, so we've got some experience with hybrid designs and also a fully remote. So this is an interventional study with a fully remote design, is the operational pieces, again, that Jane mentioned, but you don't have that fallback option. When you're operating a fully remote study, all of a sudden, your, you know, your very last resort, which is, well, if it all goes completely wrong, we don't want it to be this way, but the patient can go back to the site, 'cause they were going to go there for the other visit. But the infrastructure is there. You have not got that in a fully remote trial at all, and this patient could be hundreds, if not more, kilometers or miles from their nearest center. So you don't have that fallback option. So it has to work. Whatever that thing you set up has to work. So, you know, the coordinating couriers and dry ice and so on, you know, you don't get another option. Oh, well, we'll just bring the patient into the site the next day, which we have seen in our hybrid trials quite a lot when things haven't worked out in the earlier days. But, yeah, you really need to have these very robust backup plans in those instances. But, yeah, I think, you know, as I said, similar to Jane, we've had quite similar experiences, really. It is just those real, like, nuts and bolts operational pieces that you have to, you know, throw away the rule book, get rid of all your assumptions, and start again. There is a way through it. You just have to think differently, and we... I think we're quite used to not doing the same thing over and over, but it's a very well-practiced, very well-versed process, you know, setting up your trial, running it, closing it down again. We've done it dozens of times, but all of a sudden, you know, that rule book has completely changed, and it you have to sort of start being a bit more creative. It might not be quite such a familiar area for some people, I think. Definitely a skill that I've brushed up on recently. Stephanie? So I'm just listening and nodding. Some fantastic examples shared there. I think just going back to some of the principles, you know, don't introduce new ways from a technology and operational perspective or process unless there's real benefit for it. Of course, that's something that needs to be tangible. We need to monitor and adjust as we're going along and ensuring that we're tracking against some of the issues that arrive. I think one fundamental that's a big learning point, and I feel like this is probably a very simple observation, but make sure that you're writing in and you know taking all the different considerations and introducing it right at the beginning, so right into the protocol. I think that that's where there's been some challenges, especially when there's been some interest, let's say, in some of the optionality that, the process or new technologies provided is trying to retrofit it and go back later in the stage and make protocol amendments. That's not going to make it easier for anyone. So that is a very simple lesson learned and something certainly that we are taking into account as we're moving forward. I think also just listening, and Jane mentioned around the training, training is imperative. Training is important for the participants, but also the investigators and the sites as well. This is something that we've actually almost turned into an opportunity. So if you do bring in technology, you're able to actually access and the training for investigators in a much quicker time point, but also in a time that suits their scheduling. I mean, gone are the days where we go for the in-person investigating meetings. We can now do the training in a much more interactive way. And one thing that we brought in for aesthetics, for example, you know, we've talked about diversity. We need to make sure that our investigators are ready to, you know, make enhancing patient diversity in our, in our patient population success. From an imaging point of view, traditionally, through different training or even medical training, a lot of the training done is done on lighter skins, and so we're ensuring that our technology enables training to take into the nuances and the different presentations of conditions, but also anatomical presentations as it pertains to different race, ethnicity, age as well, and gender. We need to be looking at diversity across the board. You know, when we do talk about diversity and some of the potential challenges is, of course, it provides an opportunity to break down those barriers and obstacles that pertains to potentially some of the, you know, the proximity to clinical sites. But we also need to keep in mind, we don't want to maybe actually further cause issues with regards to divide, with accessibility to technology, but also just the comprehension of different tools. And so that, then again, is a necessary element to make sure we bring the training. And then, just on the same topic, when we're looking at, you know, capturing adverse events, and we also capture injection site responses on some of our device trials for injectable assets, we need to make sure that we are providing that education and accounting for any unintended bias as it pertains to actual self-reporting. Of course, having the real-time monitoring from a safety perspective is a huge opportunity and enables us to, you know, be keeping track safety in real time. But we also just need to make sure that the data in is consistent with regards to the context and how it's being captured and how it's being interpreted. So these are just some examples. You want to come in, Jane, please. Sorry, Stephanie- Briefly, yeah. She mentioned data, and it was a point I meant to raise as a kind of a word of advice, that get your data privacy officer involved really, really early on. If we're sort of moving through DCT to sort of digital technologies, what is deemed personal data is very fluid. So, for example, we've used some devices to measure gait and fall for Parkinson's patients, and our data privacy officer, quite rightly, you could say, if the right person looks at those, they can identify which patient that is by looking at that patient's data. So therefore, we need to treat that data in the right way. We need to understand the rules and the regulations for each country. So we've had a kind of a few false starts where we've assumed that the data maybe is-... is not, not exempt, but maybe not the same as patient-identifiable information, or we use it. We know we haven't necessarily taken that full breadth of advice as early as we should have done. And the other same similar point around data, going back to infrastructures and countries, is hosting, and I guess it's more of a cost warning. It's. Don't underestimate your hosting costs because they can be really impactful to your study budget, particularly depending on geography. So just another kind of early lookout to make sure you don't forget about those aspects. Harpreet? Sorry, Stephanie. Let's move on with the conversation, then we can come back. Harpreet. Okay. Yeah. So just quickly, just to tech challenges. Yes, I think, a lot of promise early on with some of the- Yeah. technology that was out there without real thought into what this means for the site and the site burden and also, for the patient. So it's really important, as my colleagues were saying, to ensure that you understand exactly what the nuances of that technology is. And if you think about digital health technologies in particular- If you're gonna use a watch or a sensor, it's got to be right, not just about picking up the correct endpoint, but is it usable for the patient? You have to think that through all the way. I was struck by, I think it was Jane said, you know, it's making those small... looking at the small things in a protocol that could make a difference as to just how applicable the protocol is and how, and how you can adhere to it. It's those little things that really do make a difference. And so we've definitely seen some sort of technology challenges, I think. A little bit of over-promising and under-delivering, if I'm sure that resonates with some folks. So I think it's really important just to tease out very carefully some of the risks and challenges. I think the other piece, just around operational delivery as well, the sites. We've got to engage the sites, really, we've got to support the sites really well. And again, you know, Jane alluded to it, Angela, that we don't want to overburden the sites as well as we've got to think about the patient, but also, sites don't want to be tech support. That's not what they're there for. They're there to take care of the patient, ultimately, and ensure the integrity of the trial at site. So, adding all of these factors can be very, very burdensome. So we need to think about the site contract. You know, are they being reimbursed appropriately for the work that they're doing? I think there's a line of thought that actually, you know, site perhaps is doing less work when they're involved in a decentralized clinical trial, and that may not be the case. So we've really got to look very, very clearly and closely at what we expect from a site and make sure we set it up appropriately for them. One thing that I would like to ask you all, and as usually, people in the pharma industry love to complain about regulators. What, so what- how are we doing in terms of the regulatory guidance? Is it going far enough in this field? And where do we need greater clarity? Do you... What, what has your experience of dealing with regulators in this space been like? Harpreet, why don't you start, and then I- Yeah. Yeah. So, I think we all saw that the regulators can move and be very, very flexible during the pandemic. Then we saw them all just, again, dial back up, which was a real shame because I thought we made some fantastic inroads during that time. We're getting better information now. I think there's some clarity now from the FDA around, you know, who's involved at what stage in a DCT, and how they should be trained and what their responsibilities are. I do see there's an awful lot of accountability on the investigator now, particularly coming from the FDA. So I do have some concerns about that additional potential burden. So we'll see, we'll have to see how that pans out. But I think generally the guidance around diversity plans, et cetera, is really, really positive. I think it will drive us down the right route. And again, we're getting some more, some clearer guidance around the applicability of digital health technologies, around computerized systems, et cetera. So as that develops, I think that will help us take a little bit more risk in terms of, you know, pushing the envelope in DCTs. Interesting. Thank you. Angela, what about you? Oh, just one thing. I would like us to... We have about 15 minutes left, and we, we have, I'm not joking, about 25 questions, and some of them are really, really good. So I'm going to ask you to please sort of power through your answers because there's something else I would like to ask you, then I want to move to the Q&A. But there are really, really some good questions, so thank you, audience. Angela, please. I think that the fact that EMA and FDA have both come out with guidance. Okay, it's not. There's still some room for interpretation there, but it's moving in the right direction. So I think they are both very big signals to the commitment and to progress this in industry. And also a sign that actually, you know, they are looking out for us as an industry to try and help us through this journey. In terms of guidance, I mean, I think, you know, the more guidance you can get, the better, in general. But I would also say that I think, actually, when people say lack of guidance, I think we're actually lacking a precedent more than guidance now. Because there are so few examples, and I'm actually not aware of any firm examples of studies that have used DCT, significant DCT approaches, so fully remote or even, you know, significantly hybrid, that have used this for submission purposes. So of course, around this lack of precedent is also a lack of clarity, and nobody likes lack of clarity. So, I think- to me, that's where the problem is now shifting from guidance to, yeah, seeing how this actually pans out in real life. Stephanie, what have your experiences been like on this? Well, I, I'll keep it relatively top line because I think, it's been covered really nicely by Harpreet and Angela already. I mean, I think this is where it's partnership, right? And, you know, we're all going through this process of being able to, I guess, shape the future, but it has to be set in precedence, to, to Angela's point. And I think that this is where we need to keep working forward. There have been significant inroads made, but I think that this is also, you know, where, and, and, you know, to look at it from the perspective of the endpoint development, this is where we absolutely need to work in partnership. Because at the end of the day, a lot of the.. well, the innovation is taking place within industry and, and partnerships, often with them, academia as well. It's ensuring that all of the different sets are being put in place to enable there to be an acceptance, but also demonstration of the clinical meaningful and significance. But also being able to work it back to demonstrate that it is, it is an alternative that speaks to the patient benefit, rather than just introducing technology for the sake of it. So I think that that is really clear. I mean, this is something that is, is work in progress. I think there's huge opportunities. Maybe the rate of progress sometimes can feel a little bit challenging, but at the end of the day, you know, we all need to ensure that we are bringing in measures that are the right measures for patients to be able to demonstrate ultimately what the benefit is for them and through bringing in new assets and compounds. Thank you so much. Jane, what has your experience been like, and where would you like to see more clarity from regulators? Well, I guess I was going to echo Stephanie's comment, that particularly around the kind of part of decentralized trials, which is related to endpoints or development of new tools for measuring endpoints. We absolutely have to have dialogue with the regulators. The published materials enough just don't give us what we need at the moment. But what we have found is when we've had that engagement with the regulators, they've actually been really happy to have a conversation, to give feedback, to have several meetings. So I guess my recommendation is just talk to them. Where you need more, try and talk to them. It doesn't always work, but so far, so good. Thank you so much. I keep getting questions from the audience, and I think, I'm not joking, I think we're about 25 in. So what I'm gonna do is I'm gonna combine... I'm gonna do a medley of questions. Combine one from the audience, and I combine them with the talking points that you're familiar with. And here it is: So how do the economics of running a DCT stack up against a traditional CT? What are the expectations in terms of accelerating the CT process as a whole by decentralizing the process, which kind of blends in with what are the factors behind the positive impact, the positive fiscal impact of DCTs? What are the benefits beyond cost savings? And where are the returns most compelling, and how can we measure these improved financial outcomes in DCTs? Harpreet, why don't you start answering with like- Yeah. I'll be really concise. So a couple of- Please. Couple of headlines here. So, comparing a DCT to traditional, our experience to date is you're not gonna see a big difference in terms of baseline cost for delivering that study. However, where you will see a difference, we believe, is in terms of the outcomes. So the outcomes, if those improve in terms of patient retention, you're going to save some money there in the long term. Adherence to protocol, you're gonna save something there in the long term. And then, there was a third point, it's gone straight out of my head. But generally just looking at the overall outcomes of the study rather than what's the baseline cost of the study. That's what we need to look at. What are the improved outcomes? Because that way you can see in the long term there's an improvement. We know about protocol amendments. If you, if you don't get it right up front, that, you know, that there are sort of issues around, as I said, retention, engagement, et cetera, of patients and adherence to protocol. If you can improve that during the trial by using DCT methods, and we have seen improvements in diversity and retention, certainly at ICON, then you will impact the outcome. So I would say focus on the outcome rather than the baseline budget at the beginning. Jane, what are your thoughts on the economics of DCTs? Yeah. I think Harpreet has absolutely hit the nail on the head. Our experience is incredibly similar. You know, advantages are in recruitment and retention, not in operational spend or the cost of doing the trial. I think the only other piece I'd add in is, and this is more about the digital health endpoint development, is there's potential to basically minimize the white space in your clinical development plan, 'cause you're thinking about what are my future endpoints gonna be when you're earlier in your portfolio. So actually bringing your product to market a little bit earlier. Yeah. We've got some opportunities that we haven't had before, but cost per study, I think Harpreet's hit all the key points. Stephanie, what are your thoughts on the economics of DCTs? Where do you see the biggest kind of benefits? Well, I would say, just before I go to benefit, I think, it can be, maybe, a challenge if you are just looking at metrics from an economic and, and a cost decrease, because then we're gonna lose out on opportunities to introduce into the clinical trials. And so therefore, I think if we are so reductive on that element, we will never make progress. But exactly, it is building all the other metrics and KPIs. I think there are some cost savings that can be done, and we're looking at this from an imaging perspective. So I mentioned earlier about bringing in these, mobile-based, imaging solutions, and that's something that definitely, when we look at it from the, short near and, and then to the longer term, will definitely provide cost savings. And this is something that will be very important for us then to look at how we recoup the cost that we're associated with developing the technology in the first place. And so therefore, it's always a trade-off, and we're looking at evaluating the balance there. But I think that this is where you know, by providing you know, when we when we're looking at it at home or the mobile device solutions, this will then enable us to continue to look at cost savings there, but then to continue to invest in and how we can further develop the technology. So there are cost opportunities, but it's not certainly not the sole focus. Angela? Yeah. I mean, it's difficult to follow now 'cause everybody, everybody's made the main points, but actually I've got quite a good example of which sort of highlights a lot of the things that everyone's been saying. So, definitely, it's focusing on the outcomes, not, not the top line going into your study budget. But we've got a pediatric study where we're deploying, well, again, optional, but DCT options for these patients to really reduce that patient, but also caregiver burden. And we're looking, focusing on the younger cohorts, 'cause obviously in Peds, you start with the older age groups and move down to the younger ones. Well, you know, you look at these, you know, parents with a sick child and probably traveling across the country to get to a specialist center to treat their child's disease. And offering up these alternatives, which means they don't have to do that, that journey is gonna be quite, well, it should be very well-received. So we've had a lot of input from our KOLs and patient organizations to say, "Look, this is what we want. We do want this option." And in this specific example, because, you know, pediatric studies are often part of your, well, you know, the bigger picture of pediatric development with your product's life cycle. If we can recruit an additional X number of patients, and these are small numbers, but if you can attract these patients that the caregivers just wouldn't have consented, you know, this could translate into quite big numbers. And we've sort of modeled a few scenarios and so on, and feel that we can make months of difference to the closure of this particular study, which obviously from a life cycle pattern point of view is considerable. So you know, it's a very specific example, but I think if you really can make that difference, and it just highlights Harpreet's point, if you can really make that difference to when your trial finishes, you know, there's a huge financial gain that could be made there. And more importantly, that drug gets made available to people that need it earlier. Let's combine another two questions. I mean, there are seriously some really, really good questions from the audience. So do you... Very, very briefly, lightning round. So do you engage with patients or patient organizations? I'm gonna use that as a springboard, Angela, what you just mentioned. Software—do you engage with patients or patient organizations designed to trial protocol, software education tools, and what has been the impact of DCTs on getting clinical medicines or supplies to patients? Angela. Sorry, I missed it. It cut out the last part of that question. Sorry. I can't hear. Is it just me? I can't hear Donato. No, I've lost him too. No, me, me neither. Donato, you're cutting out. Maybe between us, we could start- Yeah. on the question about insights from patients, Angela. So yeah, well, I think we talked, we did talk about it a little bit before, didn't we? And I know he was pulling on a point I'd made about this pediatric study. But, you know, I think you need absolutely. And we talked about it earlier when we talked about end users, didn't we? But, you know, you need to engage your patient advocacy groups and, you know, whatever. You need to understand the challenges for those people and what it means to them and what it is they're looking for. Because what you might assume, even as a no-brainer, you know, you might assume we should definitely do this this way, could be completely the opposite, in when it actually comes down to it. I think it's absolutely critical to engage these sorts of organizations. Yeah, and if I might add, just in terms of... We obviously at ICON, we also talk to patients as well, patient advocacy groups, and then during you know, the running of a DCT, we can also send out surveys to see how the patient's feeling about being involved in the study. But I would say that, you know, one thing that we've heard time and again around the protocol, and this isn't just about DCTs, frankly, it's more broadly from a patient perspective, is that so often protocols are all about the scientific endpoint, what the clinicians think might be useful or the scientists might think is useful, but actually, it's not gonna make much of a difference in the quality of life of me as a patient, so why do I care? So we've really got to listen to the patients. What's gonna make a difference for them when we develop the protocol? And then you can, you know, you can put that in, think about DCTs as well. What is it about engaging in a clinical trial? What will make it easier? What will make it beneficial for them? So it goes from the protocol, the protocol design, what's in it for me as a patient, but also making it easy for me to engage. I hope you can hear me now. Can you hear me now? Yeah. We can. Hallelujah. Amazing. Stephanie, would you like to come in? Yeah, of course. The patient voice is vital, and we do connect with the patient groups to better understand how we can be designing all of the different elements from protocol design and bringing new technologies. I will say a couple of things, and there's research to show that patients and subjects are open to technology and open to the difference, you know, whether that's the new digital wearables or technology being brought in, as long as there's an education around there. I think we also need to kind of keep in mind that they do like in the mainstream to have that interaction with their doctors, and so therefore we do need to enable that dialogue is maintained throughout the clinical trial, 'cause that will obviously help with retention as well. And I think also then the diversity piece, and you know, we want to be inclusive. So when we're speaking to patients, we need to keep that in mind. So one patient does not represent all of the patients within a certain condition, and so that is really important to ensure that we're taking in all the different perspectives and bringing that into what we do. And then, obviously, there is the option then to take those considerations into whether it's endpoint introduction or even just the accessibility to the tools, for example, and of course, the education piece around it. But I think, you know, that there are often... You know, the benefits are understood by subjects in the trial, but obviously, there's just about the maintenance of having that access. And, you know, there's definitely opportunities in the future as well for subjects and trials and patients then to be able to have real-time access to some of their data metrics. We're running out of time. Oh, sorry. I'm just... It's a topic that I love, but anyway, I know, I know- Very briefly, I want you to come in. Thank you. Jane, super briefly, and then- Super briefly, along the lines of everybody else, absolutely, patient insights are really key. And also investigator insights, so practical simulations from both the investigator and the patient perspective can be really useful. And the other point I was gonna make really quickly is don't second-guess what the patient wants. We think- Yeah. you know, someone coming into your home is easiest. Actually, it's an invasion of my privacy. I'd rather go out. So just ask the patient, I guess, I think is my learning there. Thank you so much. I want one, a one-word answer from each and every one of you. In what clinical phase do decentralized clinical trials make most sense? Jane. One word, one number, actually. Two. Okay. Stephanie? I say two, but I also work in device, so feasibility as well. Angela? In our experience, Three. Harpreet? Two and Four. All right. All of them. I'm going to hand over to Harpreet for her closing remarks, and then we need to wrap up because I've got- Yeah. So I just want to thank my panelists. It's been a fantastic discussion, really insightful, really interesting. Some amazing insights that have been shared, and I think we've all learned from each other, and hopefully, our audience has as well. I just want to thank Donato for moderating as well. So thank you very much, and I'll hand back to you to wrap. Thank you. Look, it's been a wonderful, super engaging panel. We're running out of time. Despite the technical difficulties, we made it through. Some really wonderful insights. Thank you for being with us. This video will be available for another 30 days. For today, that's it. Thank you very much, and goodbye from BST.