Rethinking Phase I Oncology Trials: New Options and Considerations - IQVIA HOLDINGS INC

have you here for the next 90 minutes to focus on rethinking phase one oncology trials i'm murray aiken executive director of the IQVIA institute for human data science and it's our pleasure to host this event this is the fifth year we've had a symposium here at ESMO and we are delighted to have on the stage in front of you an outstanding panel of speakers who you'll be hearing from in just a few minutes, each of whom is going to bring their expertise and insights around phase one trials to us this morning. So our goal here is to reflect on where things are, where things are going and what we can expect ahead in terms of the role and conduct of phase one trials. We selected this as the focus for this year's symposium, just given the amount of attention we would say that is focused on phase one, more so now perhaps than in the past, and a lot of moving pieces that we'll get into as we proceed through the discussion. But first, I want to run through some of our research at the IQVIA Institute that we've been doing that will help set the stage, and then we'll bring in our panelists to hear from them. And there's really five major areas of change that we see contributing to the rethinking of phase one trials. First, the shift in the nature and location of the sponsors of these trials. We've seen a lot of change over the last 10 years or so. Second, the evolution of targets and modalities being pursued in early stage research. We see the evolutionof trial design, the endpoints, and indeed the very role of the Phase 1 trial and what that means for patients, for sites, as well as for sponsors. The continued productivity challenges associated with these trials, their cost, their time, the success rates, how AI is being deployed in that context. And finally, the multiple efforts underway by regulatory agencies, as well as investigators and sponsors, CROs and others, to improve their support of phase one trials. trials. And to bring support to these points, and since all of us here I know like data and evidence, let me just run through briefly what we're seeing with a few exhibits here. So leading off with this view of the phase one global oncology trial activity. So this is, we focus on industry sponsored interventional phase one trials. This data is derived from the Sightline Trial Trove database, the left-hand panel, just the number of phase one starts, which peaked as you see in the 2021 to 2023 period. It has come down from those peak years and we can talk about what drove that if we want. But we tend to sort of compare today with the pre-pandemic baseline year of 2019, and the trial stats are up 9%. The middle panel is showing who's sponsoring these trials, and here's where we've seen the emergence of what we define as emerging biopharma companies in the top segment. These are companies that we estimate are spending less than $200 million a year on R&D. The top end are the pre-commercial ones. There's also some with commercial revenue. But at the bottom of that chart, you can see how the large pharma cohort has gone from sponsoring about 50% of trials to 17% in 2025. So, again, pretty significant shift there over the decade. And then on the right hand side is looking at the phase one starts based on the location of the sponsor headquarters, the headquarter location of the sponsor. And here at the bottom, you can see clearly the rise of China going from 17% in 2016 to 43% in 2025. US based sponsors and another 31% on top of that. And then you can see the other Switzerland, South Korea, Japan, UK, other major headquarter locations as well. But again, I think we've all heard a lot about China and that's our view of their overall presence in sponsoring phase one trials. When we look at where trials are taking place, so which countries have phase one sites, This is actually looking at the aggregate of the 2023 to 25 period European countries, accounted for eight of the top 15, led by Spain. Not surprising, but also I think important to recognize how significant Australia has become as a center for phase one trials. And then you can see the other countries there as well. Modalities have shifted towards more complex targets, more complex approaches. The left-hand side tracking the number of starts by modality. the cell and gene therapies in the light blue at the bottom, and then the ADCs, the antibody drug conjugates, again, not surprisingly, to see them becoming such a significant part of the total, and then, the RNA on top of that. Those new modalities on the left represent about a third of the TOTAL stats, which is reflected on the right. The rest coming from other biologics as well as other small molecules, which have sort of settled in at about 45, 47% of the total. The role of phase one oncology trials has been expanding, and I think we'll get into this, continues to move. And I think, we've seen a lot of movement away from finding the maximum tolerated dose to optimize the dose and the development strategy and the extent to which the phase one trial is generating data that feeds into that design of the development strategy is clearly one of the trends that we've been following more recently. On the productivity side, just a couple of data points here. We track the success rates in this case across all oncology programs. Phase one success rate around 42% on average for the last five years, similar to what it was five years earlier. This does feed into what we calculate as the composite success rate when you multiply each phases success rate through to arrive at the composite there on the right six percent on average across the past five years and you can see on the right just to show how that varies between a small molecule cell and gene therapies and other biologics again we can have a debate about what the optimal success rate is because we know that it's also a reflection of the magnitude of the risks that sponsors are willing to take with the trials, and we may get into that in a little bit. Another area that we know gets a lot of focus is the length of time it takes to enroll patients and to actually execute these trials, so this is one part of the timeline that gets a lot of attention. On the left-hand side, here we're showing that the median enrollment time for all of oncology in the solid line at the top, and then phase one broken out in the dashed line. So that comes in at 26 months. Again, median enrollment times for a phase one trial. It's down from the 30 months around the pandemic, but I know there's a lot of interest in trying to reduce that even further. I also just showed on here the non-oncology enrollment times, which I think, as we know, continue to run significantly faster than in oncology. That then feeds into the right-hand side where we're tracking the composite median oncology program duration. So again, the sum of the phases. And in 2025, that came out to 10.6 years, of which 3.4 years was the time for the phase one study. So that includes everything from sort of startup to first patient into the start of the next phase. That's how the timeline is set. And again, we've seen this number overall increase from about six years than it was back in 2016. So we know there's a lot of effort to accelerating programs, there's lot of pressure to move quickly through the phases, but it is still taking 10 years and that clearly has a consequence for patients as well as for all the stakeholders who are involved in that and then finally just a little bit of a reflection on the many efforts that seem to be underway right now around the world to streamline and accelerate the pace of innovation including in the context of phase one trials and you know it does seem that we've got a a remarkable amount of activity coming out of uh the fda uh coming out of uh brussels and amsterdam in in europe uh as well as the ongoing efforts in china uh to to strengthen its competitiveness in life sciences um and the mhra uh in in the uk is also um you know wants to ensure that it carves out uh a role for uh for trials in the in the uk other countries as well are doing things and there really is uh just you know it's what we refer to as the regulatory competition um you know amongst the regulators to see who can outdo each other in terms of helping to to streamline and accelerate programs so that's a little bit of the setup for what we want to now talk about and you know again there's There's lots of things we can cover in the discussion, but we've got new definitions of success. We've got the global orientation of trials and their sites, the operational realities that are faced in conducting these sites, that multiple regulatory changes underway, and the multiple stakeholder actions needed to optimize the impact that phase one trials can have on patients and in advancing the next generation of approaches to tackling cancer. So with that, let me turn to our panel and bring you into the conversation. of you uh is involved in your own way in uh phase one trials and um so we'll start by going down the line and and having each of you um but just briefly introduce yourself um a little more description is in the program but how you connect with phase one trails and then tell us you know which of these areas are you most focused on or you think are most important to explore in as we we think about rethinking and redefining phase one trials. And we'll start with Dr. Spira. I'm Alex Spira, I'm a medical oncologist with Next Oncology Virginia. I have a special interest in thoracic oncology, which I've been doing now for greater than two decades. For me, I think the most important part is just figuring out a way how to get our drugs faster to patients. I think what I've really learned over the last couple of years, and as a lung cancer doctor, I focus on the classic drug Wynosa Mirtinib was developed and approved now I think over 10 years ago approximately. It was a first in class and at that time it was really the only in class EGFR inhibitor and it revolutionized lung cancer treatment. And while there was a couple of other Me Too's, they kind of never really panned out. Now when we develop drugs, there's five at the same time. So we have probably 20 different rash drugs in development. We have probably added two more PDL VEGF bispecifics while we're sitting here today, and another three ADCs as well. And for me, I think we have to figure out how to optimize it for our patients, because what it is, it's creating a mess on the back end, because you have to find out which of the drugs are going to be approved, which is competitive, and with all due respect to our pharma colleagues, do we really need so many drugs that are identical? You know, our patients are our most valuable asset. And just completing these, you know, phase one is easy, but you have to get them through phase three. And we have five phase three clinical studies of all the same agent with a little bit of twists on it because everybody wants to market. And for me, it's hard because what do you do? Do we really need all these? And then it ends up being less about the science and helping our patients than marketing themselves. And we have to figure that out because it's just very, very, very complicated. And as I said, is it right? I understand market forces, right? You know, everybody should have a part. In the United States, we don't compete on price. So nobody's coming up with a cheaper PDL VEGF by specific. We're just coming up avec more of them. And it just creates a lot of havoc and chaos. Great. Thank you. Victor. Hi, I'm Victor Moreno. I'm an American oncologist, and I work at the Star Madrid Fulnathium Humanity Health Hospital, fully dedicated to early phase clinical trials since more than 10 years ago. And I think what we have seen in the data of the studies, the drugs taking longer, that's a bit disappointing to me. I think from the phase one perspective, phase ones are getting more complex. They're increasingly becoming also almost a phase two part of the study by adding backfields, in expansion cohorts so if you saw the data the phase two time is reducing it because we barely need phase two studies anymore and um i think that the the bar also what we expect in terms of benefit is higher maybe 10 years ago drugs could make it to the market with less activity but now what we really need to see is activity from the phase one study so really benefit patients and And something that I think we are missing from the data here is the biomarkers. The biomarker increase the likelihood of the drug being active by more than double of the likelihood of success. So I think with those improvements, we can make these drugs faster to patients and benefit them more. will see in the coming years more complex designs umbrella basket these are very large studies and in the end it may seem like the study takes longer but in the and what happens is that you make sure that your drug is going to be positive so it will really make it to the market and really benefit all patients not only the patients that are into clinical trials great thank you for an invitation um representing cancer patients europe there is a for those that don't know uh is a pan-european umbrella organization we have more than 100 members across europe and one of the things that we are very much into is the inclusion of patients as a patient engagement into research uh visit engagement doesn't mean that patients are participating in the study that was a misconception that we faced some years ago when talking in scientific meetings with researchers but uh uh is that the participation of patients given their experience they can include as a result new endpoints things and concepts like the quality of life that was not even considered a few years ago is now getting introduced into what is important why because uh well a patient can get that those that that physically they can tolerate but uh there are all the parts of the individual not just physically is mentally and in their lives and the long-term effects can be not variable for a person even physically they can do because that can get into difficulties in the social life and so on not going to enter into details and but we are participating in many clinical trials research projects normally academic sponsor when we're introducing that participation of patient engagement from the moment of the design of the protocol introducing things the researchers never came into the thinking when we talk about what is important for the patient well there are studies that show that only 50 percent of what the researcher thinks is the good the preference the expectation from the patient are actually considered by the patient patients have their own experience and they have things that as normal research are never gonna uh had into their minds as important or necessary to introduce but patients have to have a proper contribution a meaningful engagement for that is important as we saw that that participation as uh given all this information that can improve the clinical trial has a harmonization in terms of standardized protocols that can be followed and everybody knows what to do and how to get patients into that and definitely when you get that experience and all the projects and we've been part of with researchers give benefits for that research, the clinical trial, the increase of the participation of patients, the recruitment and so on, then you'll see that actually the patient engagement is given an extra uh positive point for the uh that outcome of that clinical trial so just i would like to get people introduced into this idea and in the next years we work together as well in the uh act eu with the ema uh as an advisory group and we're trying to introduce that uh the participation of patients into the designing and monitoring clinical trials hopefully we managed to get it done and as something regular great thanks for that and uh david yes hi david alsadius i'm a clinical oncologist and i'm head of solid tumors at the qv oncology center of excellence and we work a lot with the strategic and delivery of clinical trials and i think from what we've heard here we see that a lot across all the trials in the phase one trials that we see the increasing complexity uh both in increasing regulatory complexity increasing design complexity biomarker complexity and also in terms of delivery complexity so i think what we see is that how do we navigate all these complexities and when do we need to put them into our trials and when can we actually reduce complexity but still being able to answer the pertinent questions that we need answer to move development forward. I think we sometimes introduce a lot of complexity without having defined the proper questions first and that could actually lead to gathering a lot more than we necessarily need to answer the real important question to move forward and actually bring these drugs to patients and that will also translate into you know operational complexity which is we've heard so from my colleagues are becoming more and more complex and will require more management more people and also longer time to deliver so i think that is a important aspect that i'd like to bring up and discuss here great mohammed hi good morning my name is muhammad dar i um serve as a chief medical officer at immunocor and i've spent most of my career over the last 20 years focused on early phase drug development i agree with a lot of the comments that were made by my colleagues before i'll just share my own perspective which is i think an optimistic one thinking about outcomes for cancer patients let's say 20 years ago compared to now outcomes have generally improved expectations have moved up in terms of what you expect out of phase one both from a patient perspective but also from a clinical trialist perspective and so i think that's the that's the positive underneath it uh what what i've observed is certainly the expectations for what you want out of a phase one trial has dramatically increased the idea of just answering a simple safety question has gone away and the company that i'm at now we're focused on very targeted um immuno therapeutics and so one of the complexities that's introduced is the more targeted an agent is the more complex the trial is and I'll just give you an example if you if I remember back 20 years ago where you would do all-comer phase 1 oncology trials with a relatively untargeted agent you could run a typical phase 1 trial with 3 or 4 centers enroll 50 to 60 patients in screen perhaps 100 the trials that we're running for phase 1 because we have to select patients based on HLA and sometimes even for the tumor marker, we have 15 to 20 sites. We screen over 1,000 patients to get 60 to 70. And so I think that's the inherent trade-off of higher expectations, more targeted agents. The trial inherently gets much more complex. I think the other aspect, just responding to Dr. Spira's comment about that we have a lot of agents that look very similar. I think, you know, from a small biotech perspective, there is a high bar to bring programs into the clinic. And I think the dilemma we have is actually we have many more targets. We don't have enough resources to run the clinical trials. We don't enough patients to put on the clinical trails. So the bar is actually quite high to be very deliberate about what you bring into the clinical. And then I agree with some of my prior colleagues in terms of, I think, from a company perspective, we talk about go, no go. So we want very precise definitions of what is success for the company for a particular program out of phase one, because sometimes you can just have normal inertia. You have a phase one trial, you keep enrolling, you're looking for a signal, you keep enrolling, keep expanding. For a small company, that's usually not a viable thing. You Have to have a very clear picture of where do think this drug is going to work you want to have those targeted expansion courts at the right dose and then you have to make a go-no-go decision because it's actually in our sort of from our perspective it's good to make an early no-go because you can use those resources and apply it to a much more promising agent and so I think that's sort of part of the evolution that I've seen over the last 20 years is that ultimately this is good for patients ultimately it's moving the field forward we have to deal with the complexity because the expectations are higher and the mechanisms are much more targeted. Great. Christine, on to you. Thank you. Hi, Christine Stevens. I'm Head of Clinical Programs and Study Operations for Early Oncology at AstraZeneca. I've actually spent most of my career at Astra Zeneca and the last 20 in the clinical space focused in early oncology. And I think seeing the number of changes both within the company and in the external environment for me one of the key elements that we all need to bear in mind is the need for agility and adaptability whether that's to where the innovation is coming from what the regulators are looking for from us and importantly what patients are looking for from the treatment options that they're discussing with their physicians so i think I think as we've looked at very much the push from the regulators to enrich our data packages in phase one, we've heard from some of the other colleagues that can increase the number of patients and the time that we want to spend in phase 1. I think it does give us that enriched data package. It allows us to make more informed decisions and hopefully reduce the number of phase three failures due to having taken the wrong dose into a larger population. And I think those areas are key. And the ability to have a truly multi-regional study, bringing in data from across the Americas, EU and Asia, is also key to maintaining and mitigating against some of that timeline lag that may be seen from needing more data to satisfy both the regulators and patient needs but I think from from my perspective given the number of modalities that we're seeing and actually the shift from untargeted to targeted agents and an increase in combinations being the way forward I think that's probably some of the real shift we've seen in the time in phase one to be able to get that data to move into pivotal. Thank you. Thanks. And last but not least, Thomas. Good morning, Thomas Bogenrieder. I serve as the chief medical officer for Abalos. Abalost is a very small biotech based out of Germany. I was involved in the last 10 years in novel immunotherapies first and foremost that means personalized vaccines more targeted vaccines and at abelos now a next generation of viral immunotherapy so we administer viruses to patients and the virus works by attacking or enriching first and foremost into the cancer it's engineered that way and then it causes a very strong T cell reaction and it's a paradigm in oncology today that you need these T cells, especially killer T cells then to kill tumor cells. But that mechanism comes with, you know, as a pioneering mechanism, it comes with a whole set of problems conceptually. First and foremost, mouse data are not really translatable into humans and since this virus keeps replicating your normal pharmacokinetic form and pharmacodynamic rules don't really apply and we also don't have a biomarker to begin with that would would kind of guide us which cancer would most benefit which patients would most benefits from such a virus but i think you know that can all be overcome because we're learning as we go along but i also want to briefly mention another set of complexity that I am facing and that is investors because we're always short on cash and investors they are interested in getting a return on their investment so and they want to know when can we make an exit either a public offering or when can this company potentially be sold to a bigger pharma company so that means our phase one trials have to be efficient and lean and I think sometimes we are successful in doing that sometimes not yeah I'll stop here but that's from a really startup biotech company perspective my opinion now that's that's great and I think it's it's important to hear all of these different voices and and I think it is also important for you to Thomas to raise the issue of the return on the investment that goes into phase one trials. We also, you know, in our institute, focus a lot on what's happening in the commercial markets, issues like most favored nation pricing and so on. And there is a connection between all of this, because at the end of the day, we have an ecosystem that requires very, very significant amounts of capital to be put at significant risk with a view ultimately not only to help patients but to to actually reward that investment and that risk and i think you know sometimes we can lose sight of the the total system that has to uh uh be in sync and to work in order to continue the cycle of innovation that we've all been seen with great progress over the last 20 years, but where we need to see where that's going for the next 20 years. So I made a few notes on some of the interesting things each of you said, and so let's come back to you, Alex. You maybe provocatively said, I think you were saying, do we need so many phase one trials, which I think is a good challenge. Just talk a little bit more about how that looks as an investigator with sites and thinking about the patients, and who is it at the end of the day who decides how many of the same kinds of trials there are? Yeah, I guess what I was saying is we need more, I mean we need more drugs. We just want a little, you know, I don't want the focus to be on just more Me Too drugs. I think as an investigator, we're excited about the science. I'm excited to hear about oncolytic viruses. I'm decided to hear about novel IOs. It's where we get, you know, a lot of these Me Too drugs. It just gets really hard. And I'm thinking of a development path. You know, what do we do with all these? And they're taking up all the resources. You know? We don't, even though we're all Phase I programs, we do not operate in a vacuum. We're still working with late Phase as well. We want to be thinking about this. We want to see our drugs get to fruition. So for me, it's making sure we're using all of our resources and really focusing on new and novel compounds. I'd like to see more energy spent on that than more of the same just coming through as we try and shift. So maybe let me bring that, Juan, you into this as well because we always hear about the percentage of cancer patients who are involved in clinical research and the divide between clinical care and clinical research i mean where do you think things are and where where are they going in terms of um you know the availability and the the understanding by patients of the opportunity to participate in uh early stage trials uh well we try to uh to provide that information actually Most patients that are not linked to any association or something, they have problems, they don't know where to find that information. They would like to participate, but they don�t know how to do it. Sometimes they need more information in terms of logistics and things. So we try to provide this type of things at patient organizations to give not only some courses and and workshops and so on into the that how to participate how to prepare for that but also try to make the all the documents and available uh to put it into a plain language they can be understood so when they participate they know what they are doing so there is one uh the things that has always been uh very important for patients is that the problem with when they face the informed concern forms for instance you know there's something that in the end they sign but they don't know what they say because it's so long and the technical and so on so we try to well we already done that together with a group of patients try to refine the informed concern reforms into something that is more understandable for by patients but also giving extra support with the material that they can use to really comprehend what it's all about. But that is something that understanding and transparency makes that easier to participate. If they fear that they are going to get into something they don't know, one of the fears is that well what is going to happen in the long term if i participate into this so you have to give the honest information that they can understand and then the possibility of dropout reduces exponentially but transparency information and honesty right that is important good Good. So Victor, you talked about the need for biomarkers, but also umbrella trials, basket trials, and so on. And Christine, you mentioned combinations and so on, so can we just talk a little bit about what's constraining wider adoption of what we think of as novel trial designs, and I would say including, you know, combinations of trials that go beyond an individual sponsor's product. We do track the percentage of trials that incorporate some type of novel design, and it does seem like it's stuck. In oncology, it's higher than any other therapeutic area, but it's around 30%, and it hasn't moved much in the last 10 years. So I'm interested, and I'm also from the site perspective as an investigator as well, kind of what's going on there and how do we move this forward, again, also from AstraZeneca's perspective. So I think we need to make a distinction here between biotech studies that they are usually with one drug and they don't have a lot of opportunities to do combinations in an early stage because they have problems with funding and and actually finding partners to give them drugs so the those protocols are usually more straightforward while big pharmas that they are the ones who have these uh platform designs because they have a lot of drugs and they want to combine them all with the new asset so probably we don't see an increase in this complex design because we're seeing a decrease in the big pharma doing early phase trials they just wait for biotechs and then they buy the asset so that is probably the reason why from my perspective we are not seeing uh an increase in that area i don't know christine if you agree with me just one sentence victor thank you so much you're absolutely right because we'd like to combine our virus with other drugs but we can't afford to pay for them so we would need a bigger partner to provide us with other immunotherapies anti-pd1 antibodies t-cell engages and so on that's sometimes or most often is very difficult so i think i think you are you are right there's that element of how does the innovation in biotech influence what larger larger biotechs and big pharma are doing um i think it would be foolish to try and do all of the novelty within within big pharma i think you know having new ideas come in is is useful um from an astrazeneca point of view we're in a luxurious position we have a very strong discovery unit so we have a a blend of um in-house discovery uh drugs that are are there for us to be able to put into the clinic in combinations as well as looking for opportunities to partner and actually with the big pharma so the i think that's something that i've i've been pleasantly uh surprised to see more of i think in the early days when i was in the clinic big pharmer and big phama didn't talk to each other i think now with the the vast amount of uh complexity and uh with developing some of the agents that ability to have conversations um between the big pharma to put the right combinations together not necessarily the convenient ones that happen to sit in the portfolio i think is a is a better option for patients and um i would hope that would then reduce the number of me too combinations as well if we're looking across the industry at optimal combinations for patients and muhammad yeah i was to just add to the discussion i think from my perspective um sometimes um there there can be this desire to keep a program moving forward and if you're not seeing activity as a single agent you want to combine with the standard of care and so that i think sometimes has led to programs continuing for a long time and as i think we all know if you do now a combination and you see a signal you have no way of understanding is it um the one or the other combination partner or is it something special that's occurring with the combination so ultimately you need a randomized clinical trial and so at least from my perspective i think um the the way we think and we're sort of in the middle sort of a medium size commercial stage biotech we need our bar is high we need to see single agent activity something that confirms that the drug is working the way it is and then often the combination of partners are either driven by what's the standard of care in the disease where you're seeing the signal, or there's some mechanistic reason why you think combining with a checkpoint or chemotherapy or VEGF makes sense. And then ultimately, if you do the combination for us to make the larger investment decision, you need a randomized trial to confirm that you're actually seeing the signals. And so we've seen examples in oncology where you see a very promising signal in a combination in a non-randomized trial and you launch multiple large phase three trials getting to Dr. Spira's thing of not even me too, but that's a waste where you really didn't validate the original underlying hypothesis for the combination and as a field we launched for like three to five years multiple competing trials for this combination without really and then finding multiple failures. David, you talked about complexity as being a major feature and maybe talk a little bit about how, from a CRO perspective, you see that complexity being tackled. Is this where artificial intelligence can play a role, is playing a role? hope will play a role um just talk a little bit about you know how that complexity is is being challenged i think the complexity comes in different shapes and forms we see so we've heard about you no complexity in design master protocols umbrella protocols back fills large expansion cohorts um adaptive designs we also have very complex on the cubes you can have idc's with to try payload ADCs with complex pharmacology and then on top of that you have all of that translating into very complex delivery. I think AI can certainly help data if you have data that can guide where you want to go and especially if you had targeted agents where you know you're looking for a specific population that are driven by a biomarker and in a specific sub-population of a disease and we're seeing those shrink more and more and non-small cell lung cancer is a great example, breast cancer is a fantastic example if you look at you know the post first line endocrine setting which is super crowded now and where we're see phase one trials moving up in that space you know going in with an inclusion criteria of one prior line of endocrine therapy which actually is a vast fast fast fast population so you need data to guide you know where do you find these patients which sites can handle the different aspects of of the new targeted therapies that we have t-cell engagement with crs you need to be able to handle the crs complex adcs that might have overlapping toxicities you need ild management they might have ocular toxicity so you need all that understanding and certainly ai can help to bring that understanding together to craft a good strategy i also think that air is something we can over over rely on ai so i think it's important to handle it with scrutiny everything you get you need the human oversight you need the human governance what you get from ai but certainly i think the more complex the trials become the more data driven or at least could serve the purpose of that addressing that complexity anyone else want to comment on how ai is already or you expect will be reshaping the the phase one trial activity i'm happy to talk about it from a perhaps a more operational front but um to david's point we we do have to be mindful of how we utilize it ai is only as good as the data we point it out and the prompt that we give it um and the parameters to to pull that data so i think for me there's probably three areas that um in that operational uh and data generation uh area where it's it's going to be key and we can starting to see that come in so for me feasibility and planning it's bringing all that data together we can use um external and internal data to really understand the the way to get the right sites at the right time in the right countries to give us the data package that's going both allow the internal decisions but importantly give us the regulatory packages that we need and also understand those planning spaces so that we can be as lean as possible um with what we're doing second place is where we um our document authoring is always going to be an opportunity again those first drafts speed up that time up so thatwe can spend people time doing the the review um hopefully will bring consistency to both within the doc individual document but between um similar programs um but importantly looping in the feedback we've had from regulators and ethics so that we are constantly updating in a more real-time way um how we approach our protocols and then the third space um i think is is i'm sure fairly obvious for most people is that initial triage of the data that we're getting in, allowing some more automation of that review, looking for gaps, looking for obvious anomalies, but again, allowing our physicians and scientists to then use their skills in a high-impact way for analysis and interpretation, rather than the data cleaning elements of it. So I think they're the key ones for me in the near term. I also think just to comment on that I fully agree and another area where I think we're seeing the emergence it hasn't really come to fruition yet is the simulation and the digital twin concept and all that right so where we could actually have AI helping us doing multiple simulation of very complex trial designs and how they translate into the operational reality and that could definitely save time in the end and i also think you have to be mindful at least to me phase ones have turned into a fairly complex learning system where where we've heard that you can more or less skip phase two if you want quote unquote skip but with that i think it's also important to consider the whole chain you showed us the whole change from like from going from some early conception to actual approval if that's where you're heading and I think that is also something that AI can help translate across those different sections and Alex or Victor are you I mean we've been hearing a lot about the promise of discovery AI discovery platform companies bringing you know new science in a sense and certainly new understanding uh through i are you seeing that yet in terms of uh phase one candidates that that you're working with not yet i think it's coming soon uh you know we've been hearing a lot about it but i mean this is all i mean first of all it's going at the speed of twice the speed on flight uh i think that's going to start hitting us in the next year or two i mean right now i think they're all in the discovery and pre-ind stage but i'm sure it's coming down the pike relatively soon yeah yeah i think there's one drug that's been presented here the phase one that the drug was ai designed so but but very you know early is still in the development and and i think it from a more practical view the ai can help a lot the physicians investigators too much the records of the patients with the clinical trial protocols and that would significantly reduce the time consuming that it is to review 10 pages of inclusion and exclusion criteria and and and the ai could definitely tell you don't even you know this business is eligible it's not eligible and and concomitant drug medications that may be prohibited and and it can flag it so a lot of benefit there i mean i have a dream that uh maybe ai could convince sponsors and everybody to come up with standardized protocols and what is going to work for not only the development but for the clinic where we're doing this on a daily basis and we can all give you the example of 17 rash drugs that are basically the same on a 21 or 28 day schedule but every protocol has something slightly different and we have to build manually schedules and calendars which is fine but also sets us up to make mistakes i mean there's no repetition right i mean whether or not an ekg is one minute or three minutes we're doing something different for everybody and wouldn't it be nice because i think people will listen to ai because if it's just us talking nobody listens but if somebody listened to ai and said here's an optimal way to do it so everybody's happy it would make our lives easier and would get rid of the need for so many different pathways and if we have 20 protocols we might have 50 different ways of doing it because of all the sub protocols etc and it just creates chaos and havoc on our end and ai could probably come up with a good way to deal with it so we're happy yeah and at some point if uh we've talked about this at some point if ai is overseeing everything and making sure that everything is done right and edc's are completely normally you know everything is correct then what is the role of the cro right right Maybe do not be invited back, Victor. That had to come up. I think that's a good jump. David, do you want to? On that note, I guess somebody has to deliver the drive. And we were speaking about oversight. So I think, yeah, that's still going to happen, right? But I mean, in one sense, you're right. That automation will probably help them, you know, that make it more efficient. And we'll probably all have to reorganize again and again with AI. So I don't think that's specific to CROs. I think that specific to every type of industry that you're in. I would also say that we don't need AI to harmonize protocols. We sort of could do that already. We could have done that. And I think recognizing sort of the other forces at work that have prevented that. We need only the AI. What's that? AI. Sometimes you need a change agent. And AI could be a change engine because nobody listens to us. But if AI said, this is the way to do it, that could drive something very different and meaningful. Regulators can also be a change agent in that context, perhaps, as well. But, Juan, I'm also wondering, just from a patient perspective, because we hear a lot about patients using chat GPT and large-language models. In general, public. Yes. That is, everybody goes into asking questions and things. Yeah, I mean, that's definitely the AI is, while introducing changes that are going very fast, difficult from the perspective of the patient. Sometimes it's a bit scary, the use of data and so on, you know, who's accountable for this or that. But we also participate in many of these AI meetings with all the technical people and so forth. So AI is as useful as the learning process it goes. So the quality of the data, that means all the information there that is growing into that AI. And sometimes the information lacks the person that in the end has to benefit or not of a drug that is the patient. And if you see all the tools and things that they are trying to use AI to, in the process of the clinical decisions and so on. Well, it's always for the clinical, but never for the patient. There is no, what it should be very, very easy to use AI to give, for instance, to improve the information, the transparency, the acceptability of things. How can it improve the protocols and standardize protocols where so many exclusion criteria? Is that necessary? has a scientific evidence behind because sometimes uh well you have certain groups that they are uh underrepresented in clinical trials and we have pregnant women or over 65 and so on and uh is that actually necessary so yeah i can help you to do these things in a more responsible way and reducing that exclusion into that and you know and then increasing the participation when it makes sense. Yeah and there's something that I'm seeing a lot this last year that all patients are now asking AI you know about their potential treatments and probably three years ago they just googled it and they weren't sure what to do but now AI is telling them well there's a clinical trial here and then you can send an email to this investigator and we are probably Alex you too receiving a lot of emails from patients that identify trials and then they come to the unit and 95% they are not enrolled in that trial because we don't have slots but maybe you have another study so it's like encouraging patients to look for clinical trials and that's that's something very helpful for them yeah i think there's no question that it um as you point out ai is a change agent um you know can perhaps help us tackle some long-standing um issues uh around eligibility representativeness and and so on um and sort of lower the barriers for clinical, for phase one trials. But I want to come back and talk about another topic, China. So, you know, you saw from the charts and the establishment of China as a center for research, as well as a place where companies headquartered that are conducting uh research and sponsoring uh research um and we and i i saw the of the presidential symposia uh here at esmo this year i think five out of the 12 are coming out of china um so the the the presence is uh clear and strong i should add that we had um someone from a chinese biotech um slated for this panel but i i think they did a big deal and so she was not able to she's not coming to to um esmo um and certainly the deal activity um has ramped up uh dramatically um you know over the past 12 months and and even you know the most more recently in the last six months or so so we see a lot going on um some see this as a threat uh in some way some see it as an opportunity um some see it as just a lot more me too's and a lot more sort of opportunity for um you know incremental contributions other see the opportunity for um for more breakthroughs and first in class coming out of china but interested in your reflections maybe i'll ask christine to start because i know china is an important center for um for your company's research um and others but i think your company is uh out in front relative to other um multinational companies what's the thinking here certainly we we do have a large r d unit out in out in china um i think with the with the advent i think of a more progressive regulatory environment in in china it has encouraged and allowed that kind of almost explosion of biotech in that space. I think as well, it's easier than it was 10 years ago to start up studies in China. We're now able to include them in our first time in patient studies just due to that reduced timeline and the regulatory hurdles being a little bit easier to navigate. So I think, again, back to that agility and adaptability, we all have to adapt to the fact that that is where a lot of the innovation is coming from. And if that's what's going to be the best, those are going to Be the best options for patients. That's what we should be looking at to pursue. I hope it also encourages innovation elsewhere. It maybe has given everybody a little bit of pause for thought uh about how they can emulate that kind of um biotech um drive forward really um from from china but we will continue to to partner and work there um you know across our global studies anyway i mean we've always done that um it's usually been in that phase three late stage it's meant we used to have to do um specific uh pk studies in the same way as we used to for Japan, but again bringing that adaptability and the really planful designs into space we can have those to the multi-regional studies from very early now. Anyone else with some observations, experience from the hub? Yeah, I'm happy to comment. From sort of a commercial stage biotech company, we view China not as a competitive threat but as a way to collaborate and accelerate innovation. And there are several areas where we're beginning to collaborate. One is in early R&D. They can just move much faster to get a molecule to get R&d ready. I think the other is on manufacturing. They already had scale and they are now even faster at producing uh um clinical grade material for clinical trials and then i think the new area for a biotech um obviously large pharma like astrazeneca have been conducting clinical trials in china is to actually generate initial phase one first in human data to de-risk a program um if it makes sense um and how to integrate that with ex-china clinical data right i think it was one of the prompts around this you can generate data quickly you need to make sure it's representative of the larger population so we clearly view it as an opportunity to just accelerate the entire ecosystem you just have to figure out how to collaborate efficiently i think you know you don't have to take off my investigator hat you just everybody wants their own country to be successful right and nobody wants to admit like the auto industry like computer industry that we have fallen behind for whatever reason be it we're expensive be it were slow whatever it is and I think it's just a reminder that you know these you know the United States is still also the biggest commercial market so in some ways I'm speaking as an American we would you know the drugs should be developed here we should be investing our own resources to do that obviously we're collaborative and that's where things have to be done but it should cause us to look internally and figure out why what are doing wrong because you know it's another thing that the war you know you're losing to somebody else and again there's nothing to do with oncology but it's why we need to look and figure out how do we make it better for our you know so our kids can become engineers sorry kids you become scientists so our kids become phase one doctors right we're losing out and everybody just needs to look at that not from an investigator perspective I think I mean Part of this is also, part of the rise of China is also triggering some of these responses by the regulatory agencies and governments. And maybe we can talk just a little bit about what, if anything, you're seeing so far coming out of initiatives. In the U.S., we've had Project Optimus for some time to really focus on optimal biological dose in phase one trials. We've now got this project trial blazer that has been initiated that includes the expedited IND pilot program that's sort of ramping up. And then we've got in the U.S. this new ARPA-H slash FDA initiative that's called SURPASS, which is Simulation Augmented Real-Time Platform Adaptive Seamless Trials, which sounds like Nirvana. but certainly a lot of attention in the U.S. to try to strengthen the competitiveness, restore the competitiness in that context. What's your optimism for how these are going to play out and what impact they might have? I can start. I mean, I think there is some optimism there, but it's not an isolated room. I mean, the challenge that we have is, and I will say, you know, it is hard, you know, the United States' accrual to clinical studies has hovered around 3% for the last decades. And if you ask, I'm sure if you asked our colleagues at AstraZeneca and everyone, the biggest challenge is the phase three. We can do phase ones. We just can't do the regulatory studies here because nobody wants to enroll. And it's partially the patients, but it is getting harder and harder to get physicians to actually want to spend time to enroll patients on clinical studies and to find people to want to do this job. So there are regulatory hurdles, but what we have to do is investigators. And I'm not just talking about phase one because we do this for a living, but it's really hard with all the regulatory stuff. But if you're trying to get somebody to enroll on a later stage study, the training, the paperwork, the follow-up has got to be so complicated, they can make an extra, they could spend less time and go home an hour earlier by just putting them on standard of care. And we have to look at this as a whole because, you know, I don't know what it's like here for you, Victor, but I can't find doctors. I'm having a tough time finding doctors to actually do what we want to do. And where is that going to be? Because none of this works if we can't get those patients on. So I'm very excited about this, but it has to be a sea change because the entire soup to nuts change is how do you change this going forward? And there's a recent editorial, the New York Times, a whole article, David Hong, who everybody knows, was commenting on there. But there has to be a sea change of what do we do and how do we make it easier from everyone. The regulatory framework, sure, but it's everything going forward. Yeah, from the European perspective, with the cities, that was a major drawback. The times for Spain for clinical research were worse than before. So now the European agencies are definitely changing. They are creating this fast EU. The Spanish agency created a fast track for phase ones that are coming to Spain. So definitely the regulators need to be aware of this. And I think that's the reason because why the sponsors are going to China. US has its problems. Europe is having problems. And now they are realizing it and they're changing. so i hope that now things will go back to normal and i agree with alex finding clinical investigators is becoming very hard because doctors are seeing very complex the clinical research so unless they they have to be fully dedicated to clinical research and that is becoming very difficult and Thomas you have a sort of novel viral approach here what's your experience been in interacting with the regulators in advancing this into the clinic surprisingly very good you know in Europe if you have these kind of new advanced drugs you tend to interact with the parallelic institute in germany especially if you are a german company and there i have to say they were quite open to our suggestions most of the issues were not so much about the biology and the medicine and the and the trial design but rather they had lots of questions about cmc meaning the manufacturing of the virus and i think those questions were legitimate but they were also offering a solution so i was quite pleased with the way this this happened quite efficiently yeah the thing i would add on this topic is the ivdr legislation from eu has been a big drag on phase one trials the the regulations have made it very difficult for small companies to meet all of the requirements to try to validate a diagnostic at a stage where you you haven't dosed a single patient. The framework and the mentality is coming from, I think more late stage development when you actually have validated the target, you have an understanding of PK and you have some understanding of is the drug working, but that burden has made it very difficult to open clinical trials when you have a diagnostic, which we do, it's HLA restricted in Europe. So it's slowed down and that's a little bit, a concern in terms of that needs to be reformed i think we've seen that especially in europe but where you've tried to harmonize regulatory or regulations but still keeping especially here the country level regulations as well and and you know that has brought extra layers and again adding complexity we're seeing that with the ibdr and and i and that has also of course not I mean that might even slow down the process as we've heard from the other panelists here. Completely agree with Mohammed. I think it's not just biotech that are having to make different choices when we're selecting countries for our first time in patients. Being a European country and company really in ethos, it's been difficult to move away from our established relationships with with europe um in those very initial stages and we are almost forced where when we need to do patient selection to think about um obviously the the us australia and asia for our very early elements and i know being um in on the at the ground level is so important to to some of the science that's ongoing in a lot of the institutions um so we're hoping that at least there's some um consistency comes across europe so that it isn't still at individual country level because i think having that level of predictability that at east eu ctr will will give us um give us that um i think will be really helpful for us to be able to continue to work so closely with our our colleagues in the eu the the regulators in europe are totally aware of that and i was in a meeting last week with the spanish agency and they are uh proposing to change the the process so the part one of the submission which is the scientific and they will just be analyzed by one country so you don't receive comments from three countries and and that that was that was very problematic so hopefully those changes will become soon yeah i mean i think i think uh because we're involved in some of those conversations um as well and i think the the openness and the awareness of really understanding the the constraints um has never been higher which is which is good news especially in europe but also uh in the in the um in the us and i i think just to you know for muhammad you know from a for the u.s based um biotech companies that are not putting sites in europe that are not even uh and then subsequently registering their drugs in europe there's a lot of attention on understanding exactly why that is and what's going on and i think this is an area where really sort of digging in to some depth as to um why that is the case uh will will help um you know sort of reshape some of the the practices the uh guidances and so on that come out of europe so i'm actually quite optimistic that um you know we're at a point where the openness to uh new thinking is has never been greater so that's good so we always as you saw earlier at the IQV Institute we like to measure things and we like to sort of put numbers on on things so so that we sort of get beyond the sort of qualitative assessment and and maybe come more specific so I want to challenge everyone here to sort talk about by what measure will we be able to say that we've succeeded or made improvements to the design or the conduct or the impact that phase one trials have in three years or five years, somewhere in that kind of timeframe, right? What is it that you would look to as a measure of progress that we will take note of and then come back here maybe in five years' time and see how we did. So it's got to be something tangible enough that we'll be able to know whether, in fact, we've made change, we've seen the progress that we all dream of or hope for. So start with us. Thanks for letting me go first on this one. number of drugs that lead to approval. I mean, at the end of the day, it's, you know, somebody I know says it's points on the board. And that kind of reflects the success of, you know, are we picking the right drugs? Are we actually doing the right thing? And there was a time, maybe about eight to 10 years ago, when money was more free-flowing, and there was a lot of drugs, that clearly were just a hope and a prayer. I mean, it was all a hope but a prayer, but they were really a hope in a prayer. But are we able to execute phase one clinical studies? Are we able to find the appropriate biomarkers were applicable? And are we to get them through phase three that it really matters? I mean, to me, that's it. I mean how successful are we? I think it's never gonna be 50%. I think you said it was like three or four percent. But if it goes from four percent to six percent, that's a 50% increase. That means we've done something. So to me that would be a about marker yeah okay yeah well um i think that in the end we want to benefit patients so i totally agree but from clinical research number of patients enrolled because that means we have more trials more drugs to offer them and and the variety the different targets and different molecules well uh i think the drug optimization that means the well not just precision into the the mechanism that it's doing but also the how to adapt to individuals here we can start using as well ai with all the information from specific patients into what is going to be the best not only because they have specific biomarkers or so but also other conditions that are surrounding the patient and i think that's going to part of that optimization is it something we can measure Yeah, I think there are, well, now it's been more introduced, but something like the acceptance from the patient point of view, there are different ways that we are doing, measuring that, how is the quality of life of that person. But in general, well we can have less side effects into that with the benefits for the healthcare system as well, you know, where patients don't have to go so often to the hospital, these type of things, you know, is in general. David? From a strategic perspective, I'd say time to critical decision. So I think that, you know, and also that entails stopping or expanding or going. And I think there is also something that we see in your data, right? And would probably like to see, you And I wouldn't be disappointed, I'll put it like that, if the stopping actually increased a bit. David took mine, so I'll just elaborate a little, because you wanted specifics. So this is actually an initiative within our company, which is to reduce cycle time. And so you showed, I think, in your opening slides, the average time for phase one is a little over three years. Our goal is to get to a decision out of phase one in less than two years. Okay, great. Difficult being near the end of the line, I think I'll build on both David and Mohammed's areas really. I think to enable better and earlier decision making and to reduce those cycle times, I'm hoping actually that we can deploy some of the emerging technologies, listen to what's happening at the sites and the regulations and try and make life a little bit simpler Dr Spira for your to enable you know more interest from physicians in coming into this space which I think in turn will support an increase in the number of patients who both have access to a clinical trial which is often the problem but are also comfortable to be able to do that and we we provide those facilities to to do that yeah Thomas I can predict what yours might be. I think everything has been said and I completely agree with entirely everything that has been set during the last hour and 15 minutes. So I'm going to say something a bit different. If I look at the numbers you showed about how Europe is clearly falling behind in terms of clinical trials, biotech and so on, I think we need to look at a root cause for that and um my feeling is i don't have the data but my feeling is it's clearly a lack of venture capital here in europe compared to the u.s and now also china and i feel that often because you know often you get offered the molecule from a chinese company and the money would already come with it to develop in the western world and i think if we want to keep up also in the interest in the interests of our patients in the end uh i think we need to look at the root cause as i said and and take uh draw the right conclusions from that and i think that can be measured you know how much money pours into biotech can be clearly measured right great um yeah sure that actually are able for the patients to be used as a, to be offered as a therapy. Because I actually can go to the hospital. Right. Yeah. And that is something actually that IQV attracts pretty closely. and also, particularly in Europe, the delay for European patients to be able to access drugs that are available elsewhere in the world, in particular in the US. So thank you for that contribution. So we've had a very sort of harmonious discussion here. Maybe in the last 10 minutes we can shake it up just a little bit more because I'm interested to get each of you to talk about what you would like to see more of from someone else here on the stage representing a different part of the ecosystem so from investigator what would you like to seem different from from sponsors sponsors what do you we want to see different from investigating. You're making me first go again? What's that? You're make me go first again? Maybe we'll start on the other end, if you want. And again, because I do think we don't often get sort of democratic meetings, so to speak, where we can actually voice some of these issues or concerns to each other. So I think it can be a healthy dialogue, let's call it that. All right, so I think costs are really a problem, especially when you're a small startup. As I mentioned already in my initial statement, I would at least hope that costs remain stable, because costs for trials have really exploded, it seems. And I'm sure you have better data than I have, but certainly post-COVID, costs have exploded dramatically. But that's number one. And from a very egotistic perspective, and I'm looking at Christine now as a representative of big pharma, I would hope there would be more open for collaborations. I think small pharma companies often have very interesting assets that could make a difference to patients, but it's sometimes very difficult to have access for big pharmas, for reasons that I often understand, to be able to collaborate with them or get some drug supply for an interesting combination, let's say, not necessarily for free but for a reduced price, because we all know a lot of the novel drugs are not cheap. So that was there would be my main wish One do you want to jump? Yeah, well your friends on all sides. Yeah Yeah, we do yes well for me the from our perspective is always that to create a proper framework and structure that and this would be that with the sponsors to introduce really a standardized ways of how to collect the patient perspective to make patients part of that process in the from the design of protocols to the monitoring of the results and definition of endpoints what is important so but in a very structured and formal way that is a meaningful contribution that has to be measured as well how it's been introduced into the whole process and the patient can receive the feedback and know and the whole thing is well defined but it has to be like that otherwise it's always there the danger of just participating as a tokenism just the quality. But I can see how that can work quite well with large pharma, because large pharma does have greater resources, but again two-thirds of phase one trials are being initiated by smaller companies, so I guess what do they need from you to... Yeah, that is the same, that we also collaborate with many small research academics and so on, and small pharma companies can come to us as patient associations and we can provide help in which ways we can do and how can it be our contribution with trying to design templates and things guidelines to help not only patients but also researchers and investigators and how to introduce patients into that process and we can provide that information we can bring patients into the sometimes small companies they don't have their knowledge of how to reach patients right you know where can i find them how can i get because also to reach patience you have to know the channels right how to return but in in a way that i feel familiar for them otherwise can be difficult to get that so we can provide that uh that support to the small companies as well so muhammad do you yeah no i um i agree with what's been said i think um i'll just expand a little bit on costs so i think cost of clinical trials um are not occurring in a vacuum they're occurring in in a larger context of healthcare delivery. And so we know that whether it's the US or Europe, there are challenges with healthcare delivery, and I'll just call out one, which is we were talking earlier about conducting ultimately phase three trials, and often there's a control of standard of care, and sometimes you're even combining with standards of care. Well, a lot of the rules in terms of reimbursement are that just because a patient is enrolling on a clinical trial, receiving standard of care, they're not going to reimburse that. Well, that astronomically, we're not talking about a few million dollars. We're talking about tens or hundreds of millions of dollars. The trial goes up when you're trying to include a patient on a trial that's going to get standard of carer. And so I'll just highlight that as one of the challenges, both to slow down trials, to have underpowered trials, trials that take much longer because we are operating trials in a larger healthcare context, which is not necessarily geared towards accelerating clinical trial accrual. And, you know, one of the challenges for patients to go on clinical trials, certainly in the U.S., is that there's not a financial incentive to refer a patient to go a clinical trial if they can get standard of care that you can get reimbursed. That's a barrier, but it's a challenge to moving the field forward, especially whether it's early phase or late phase clinical trials. One of the reasons things are so expensive is, I think, bureaucracy. And from a site perspective, the amount of—you know, COVID was interesting, because we actually asked a very simple question, why do we need to do all that we need do? And things got simpler for about 18 to 24 months. We have now reversed course entirely, and from queries that are generated to 50-page consent forms to signing EDCs—I got told I had to sign EDCs weekly the other day—to bureaucracy that we have to do that is time and that is money and that is stuff that we have to do to answer and i always ask the question why what are we you're asking me to spend two hours hunting down some data that really doesn't matter for the integrity of what we're doing um and part of that is victim the usual line zeros like you know you wonder sometimes sorry I might lose my job today, but you wonder why we're doing all these things. It has gotten so hard. And, you know, part of the reason we can't find investigators is the paperwork we have to do. We understand that there's a regulatory framework and we have to provide for the integrity of the data, but there's extremes. And I think we've gone from one extreme to another right now that we probably spend more than half of our time on paperwork and bureaucracy rather than fundamentally just taking care of patients and put people on stage. Yeah, I have to answer that. I fully understand what you're saying, but I also think it's rather simplistic to just put that on CROs because, of course, we need to adhere to all the frameworks. The CRO is just the... They're the ones taking the heat for all this. I have two particular requests. It's the simplified feasibility questionnaires. We don't need to complete everything. How many refrigerators do you have? And second, don't have wait lists for patients. Patients can't wait. We need slots for sites and the site can decide the patient and the patient will be enrolled in a clinical trial, but there are sponsors or CROs that say, no, we'll put their patient in a wait list. This is something we really need to get rid of. Totally. All right. Good. I think that's a healthy amount of back and forth, so thank you for that. So we're just going to have a final sort of parting comments as we wrap this up. And we'll start with you, Thomas, and come down this way. Just sort of final thoughts, reflections, takeaways from the last 90 minutes. I thought this was excellent. It's the first time I'm doing this, and I learned a lot. And I thought, this is an excellent discussion. please let's have more of this to hear all aspects of people involved in clinical trials and bringing the next generation of of medicine to patients thank you good thank you yeah christine definitely echo that um learnt a lot and i think having these type of fora where where we have got all the different different players perhaps we're missing a regulator maybe more than anything else i think it does um inspire more rounded discussions rather than when there's two parties uh in there so uh thank you for that right great thanks yeah i'll um echo what i said at the beginning i remain optimistic that the field is still moving forward um despite the despite the challenges and ultimately all of the different stakeholders want the same thing which is what's right and what's best for um what's best for patients and i i truly believe that certainly in my lifetime a lot of the common cancers will become chronic diseases because when i finished my clinical training stage four melanoma was a disease that you the median survival was less than a year and now we have patients with metastatic disease that are living for a decade or more so i i leave with an optimistic message great thanks i second that and i i think you know i've been an investigator i've I've been a farmer and now I'm in a CRO. I also think what's been clear to me is that, yeah, we can do a better job, but we still have a very important task of bringing sponsored studies to our great, great sites. Juan? Well, I would like to go back into the question from the audience, and it's definitely true. In the end, is this got improved to reduce inequalities? i think in european there is a huge gap that we have to think at the moment of the clinical trial how can we also make that this indian is going to get to all patients in europe uh not to talk about it also the open clinical trials to eastern europe where there is also a huge gap but how can't we do to create something that is going going to be affordable for all patients we have just one mention that we have members from some uh eastern europe countries where they said well you know we're talking about the personalized medicine in my country there is no talking about that because nobody knows nor even the oncologists don't know about that right so and we're talking europe yep we have a long way to go yeah yeah thank you no thank you for this i think it was also great i agree with everything we we i'm also optimistic i think we all need each other sponsors, CROs, sites, patient advocates and we all need to adapt to what is coming. I think perhaps for next year we will also need a regulator here because they are also a critical part of all the clinical research we all try to improve and sometimes it's the tight regulation in Europe, for example, that is sometimes hindering this. So thank you. I mean I think we're all in agreement here. We're all for the same goal and I think if we all sat on the table with an FDA and EMA regulator and a couple of beers we would fix all the problems all right so with that with that optimistic note um you know a final thank you to each of the panelists you've been very generous with your time coming here and and sharing your thoughts and perspectives i very much appreciate it from from our perspective uh thank you the audience for your um interest and uh with that we i know everyone has a busy day ahead so we'll we'll close and uh again thank you very much