Lausanne VII Day 3: Global Clinical Trial Support Platform

Lausanne VII Day 3: Global Clinical Trial Support Platform

hello everybody and welcome to this session entitled global clinical trial support platform connecting north america australia and europe my name is lynn hughes and up to three months ago i was vp and global head of therapeutic strategy for quintiles iqvia i was there for 24 years and have been involved in more than 120 global alzheimer’s studies in phase 2 and phase 3 over the last 10 years before i introduce our session i would like to ask our distinguished panelists to introduce themselves please john please could we start with you of course thank you lynn uh my name is john dwyer i’m the president of the global alzheimer’s platform american not-for-profit dedicated to reducing the cost time and improving the effectiveness of alzheimer’s clinical trials i have a pronounced family history of the disease and took this job at the request of our board six years ago uh and had been uh had the privilege frankly uh of working with the rest of my panelists on a number of studies in an effort to uh achieve our mission uh and now you chris thanks john i’m a neurologist and a researcher i’ve been in the research field in alzheimer’s disease and dementia for over 20 years i’m the leader of the australian dimension network which has recently been established and one of the main aims is to facilitate entry of participants into clinical trials and really boost the clinical trials work we’re doing in australia so it’s a great pleasure to be part of this initiative because i’m very enthusiastic about australia joining with the rest of the world in this global clinical trials platform so i’ll pass now over to craig thanks very much chris hi everyone my name is craig richie i’m a professor of this country of aging at the university of edinburgh here in scotland uk um practicing psychiatrists today we can still work in a brain health stroke memory clinic um it was the academic lead for the epad program the european prevention of alzheimer’s dementia program and a lot of experience in undertaking and designing clinical trials and over the last i guess two or three years we’ve been working really closely with gap in terms of setting up a network in europe of uh trial sites for alzheimer’s studies thank you so why are we here today then in general alzheimer’s disease trials take too long to complete the average prodromal trial takes just under five years from start to finish and if you compare this to a cardiovascular trial which is on average one and a half years on an oncology trial at 2.3 years the screen failure rates as we can see from this slide also very high and more than 80 percent for a prodromal study that recruits amyloid positive subjects compare this to an average of a screen failure rate of 23 in cardiovascular studies or 28 on average for oncology trials these high screen failure rates and long timelines drive the cost of 80 trials well into hundreds of millions of dollars significantly more than trials in other therapeutic arenas and also there can be a lot of variability in our clinical trial populations therefore there is a need an urgent need to develop a global harmonized network of high-performing sites that are able to start up rapidly that have a higher return recruitment potential and reduce the variability by having less sites and more patients by sight and utilize blood-based or digital biomarkers early on in the screening process to reduce the screen failure rate the global network will have both tactical benefit higher recruitment rates shorter timelines and also a strategic benefit which is engagement with key health authorities at an early stage of drug development we already have such a network developed in the us and john will share thoughts on this network and then chris and craig will discuss how we are going to implement this in australia and europe so john if i could hand over to you please thank you lynn when we started the global alzheimer’s platform in north america we made a conscious choice at three levels the first was we were going to create a network of highly motivated clinical trial sites dedicated to our mission second we were going to make sure we had a heterogeneity in that network so we could integrate and you and communicate the best practices of both the academic sites and the private commercial sites which are very different in nature in some respects but both fiercely loyal to the mission of finding a cure for alzheimer’s and the third was we were going to take it upon ourselves to try to help streamline studies and communicate with sponsors about the ability to better implement a study by listening to and advancing to the needs of clinical trial sites on a systemic thoughtful basis because the heart and soul of the success of clinical trials is indeed uh the networks the sites themselves individual leaders who are all pulling together for a common purpose in the united states and canada we now have 80 over 80 clinical trial sites dedicated to the proposition of undertaking studies faster with higher quality and a keen interest in reducing the cost and time associated with it our first step in the united states was probably the most material in that we were able to get everybody applied to a single institutional review board which turned out to be the first of its kind in alzheimer’s disease that plus a various number of other tactics that we’ve been done in partnership with our sites has led us to great strides in reducing the time of startup sites and the corresponding clinical trials we are now in a total of eight studies using the tactics and startup our overall uh observation from that first phase building a network and startup is that sponsors need to listen to sites and recognize that their on the ground environment is different at every site and yet we need to get uniformity and reduce variability across that network that comes with communication and anticipation of serious roadblocks at an early stage the other area that we’ve advanced on is taking on a suite of recruitment tactics offered with a joining a broad set of customized recruitment tactics by site all intended to improve recruitment screening and randomization against the average of the field when you can do these things in partnership with sites and sponsors you can get great results and on balance already we have consistently shown a improvement in performance so that in our last studies we have seen a doubling of recruitment a doubling of screen rate and a 25 to 30 percent improvement in randomizations in our latter trials using this combination of tactics most importantly led by our own face-to-face visits to our sites to advance the sponsors protocol at an individual face-to-face level now in the face covid we’ve done that more remotely well we’ve made some progress but progress alone is not enough to really help the field because we want to reduce trials by a year or two with the application of even better processes which my colleagues will talk about i would only say that as we move for a global approach we need to do that with a similar respect for clinical trial sites an enormous cultural sensitivity and a firm understanding that using blood and digital biomarkers to better assess and characterize patients we can double or triple the effectiveness of our early learnings in north america and with in partnership to my colleagues today and others across the globe we hope to provide create a global clinical trial network that will uh eventually pull much more than just 100 million out of studies but uh tens of millions in any kind of study and reduced time by six to uh months to a year a huge uh contribution to the field and now to execute on how we can do this in australia i’d hand it over to my colleague chris thanks john uh first i’ll just give a bit of background uh as to clinical trials in australia [Music] uh jeff cummings i think in the past has referred to a lot of clinical trial sites as mum and pop operations i prefer to use the term hobby operations and unfortunately in australia that’s a good description of the majority of clinical trial sites in this country so there’s a lack of standardization a lack of professionalism and a lack of networking that results in delays terrible problems with individual site governance approvals no consistency from the various hospitals etc where most of these trials are run in their approach to governance and their turnaround times consequently huge delays getting trials initiated and i think something like the global clinical trials platform will set the standards uh will show those that are dragging their feet and lead to faster implementation of better quality trials other problems we have in australia a late diagnosis of patients so that by the time people get a diagnosis of alzheimer’s disease they’re often too advanced to be included in clinical trials this tends to be a lack of interest in clinical trials mainly amongst clinicians who are a bit nihilistic and also to some degree amongst patients and we need a formal and sustained educational program to increase its enthusiasm and referrals to trials i’ve mentioned the slow governance most trial sites are in public hospitals it’s not seen as their core activity and we need we need to change that attitude we have high screen failure rates like the rest of the world there’s an aversion to lumbar punctures in australia which is common to certain countries but not all and an educational program uh and standard setting etc would be helpful in overcoming that i’ve mentioned the hobby trialists where there’s a very loose network here but no professionalism and that’s something that really can be improved by participation in a global clinical trials platform we do have a bit of a problem with experienced raters from time to time again the training and standards offered by a clinical global clinical trials platform would largely address that issue and finally australia does tend to be a country that comes late to trials it’s got a reputation for good quality once it’s in but i’d like to well i would hope that australia would be one of the earlier countries uh initiated into clinical trials going forward through participation in this platform so governance efficiency can be improved standards can be improved professionalism can be improved networking will be improved earlier participation of the entire nation in clinical trials uh techniques to reduce failure rates a part of some of the very exciting work we’re discussing within this global clinical trials platform uh i have introduced a system in australia through the australian dimension network where we do offer free amyloid pet scans to clinicians in their patients that may be suitable for clinical trials this is a carrot to get them into clinical trials once the patient is shown a pet scan of their brain full of amyloid they are very highly motivated to participate in a trial and we then have these motivated amyloid positive persons to refer to clinical trial sites reducing the screen failure rate we are discussing the use of the plasma blood biomarkers as another way to improve not only earlier diagnosis of patients but also identify patients and reduce screen failure rates in clinical trials [Applause] the australian dementia network uh has been set up through six of the major cities in australia we have screening sites and these feed the patients into various clinical trial sites another fundamental benefit from this sort of networked approach is to help the financial viability of these smaller operations which can be a problem if there’s under recruitment in fact it’s a very frequent problem and is one of the reasons that clinical trial states tend to drop off the map so in summary i think the global clinical trials platform will benefit australian participation in clinical trials in numerous ways and i’m greatly looking forward to uh trying to facilitate australian involvement in this great endeavor i’ll like to hand over to craig ritchie for the european uh position thank you thanks uh very much chris i think for many of us we’ve been involved in undertaking delivering clinical trials and in some ways designing them too we realized that a clinical trial is always going to be a trade-off between the scientific the the methodological and the feasibility and i think what often drives what actually happens in the ground with clinical trials how feasible that trial is and chris alluded to this earlier we we often want to do trials in earlier populations where the disease is less progress but they just become unfeasible because it’s very hard to recruit into those and i think what we’re trying to do with the global alzheimer’s platform in australia north america and europe as a starting point is trying to take sort of make everything more feasible by having a better network and that would include better rater training better access to um to to to registers and people who are pre-screened and that that was in effect if you like the problem statement that led to the epad programme being developed the european prevention of alzheimer’s dementia which was funded by imoi through the european union and it was luke and said can we find a way of identifying a very large number of sites a very large number of people who are very well characterized to improve the efficiency of delivering clinical trials and to a certain extent we were successful in that we developed a large cohort a readiness cohort and one of the key assets that we probably delivered was a very large site network across europe uh of almost 30 clinical research centres have all delivered really well at least into the cohort study which should have then transitioned into a platform trial um that asset is something that we really want to to leverage in terms of how we uh take uh forward the gap initiative in north america uh into europe and there are there are challenges of course in europe um as there are everywhere in the world and all these europe is not one place you know europe has 30 uh odd countries different languages different cultures different socio-economic backgrounds etc so going into europe is really almost like a sort of a microcosm of globalization because of all those differences and but there are similarities of course as well and what we want to do what we have done i should say is we’ve run a survey sponsored and supported by gatt and d-pad and we we sent out a questionnaire to 56 sites that we’d identified through epad and we got incredible response 52 sites replied to say how interested they were in joining a gap network and identifying what they saw as the key issues and the key issue that came up and 82 percent of people who responded was recruitment it was it was the one thing that was really fine they found was holding them back in terms of delivering trials governance and other aspects were also there but the number one was recruitment and one thing i think really is is necessary if we’re going to have a sustainable clinical trial network in clinical plant delivery is to try and somehow bring together clinical research with clinical practice we do trials and people with chronic alzheimer’s dementia because those are the people who come to see us in memory clinics and one of the other initiatives is part of this davos collaborative is healthcare readiness and i think if we can work out a way to set up clinical services for people even earlier in the course of alzheimer’s disease and do all of those assessments there what one finds is what we call screening in clinical trials is what we call early detection and clinical practice and i think that’s how we need to dovetail the clinical trials with the healthcare preparedness and that’s something i think this part of this initiative we’re really excited about but having this dialogue with gaap and you know coming coming together over these issues is absolutely fundamental it’s absolutely critical because there’s no way we can develop therapeutic interventions for people with early alzheimer’s disease or prodromal alzheimer’s dementia without a real game-changing initiative like this to to really make a difference so i’ll stop there and i’ll hand back to them thank you gentlemen i think it was great to have the successes that gap network has had across the us and hopefully we can take the learnings from the gap network in the us and apply across the globe australia europe and then the other regions globally to get this network up and running so that we can expedite drug development in this disease just like to start with some questions now in the q a session and this one is aimed at chris in australia and i’d like to know chris if you could explain to us why you are so enthusiastic about introducing this model into the australian clinical trial sites thank you lynn uh as i mentioned many of the clinical trial sites in australia are what i call run by hobby trials and they need help they need help dealing with the bureaucracy in this country uh and something like the global clinical trials platform by introducing standards processes procedures will help that will reduce the burden required required setting up a trial the sites need help with recruitment inadequate recruitment leads to financial non-viability i’ve introduced something through the australian dementia network that has helped somewhat with recruitment but i think a broader global approach would be beneficial i’m also particularly excited about the prospect of introducing new technologies and the global clinical trials platform supporting that that can help us find and patients earlier and reduce the screen failure rates so extremely enthusiastic and certainly look forward to working with the global clinical trials platform thank you chris we’re now going to continue this discussion in live q a thank you everybody thank you we’ve already had our first question coming in which is what is your number one goal for 2021 and can you speak to how the covid studies have affected the alzheimer’s site capacity and i’d like to start off with craig so he can discuss this question regarding the european site networks yeah thanks lynn i think there’s two parts the question but there’s one answer i think the main goal for 2021 is to is to reopen our research activity to do alzheimer’s trials post covert i mean obviously the last 12 months or so and we’ve seen a massive prioritization of covert vaccine studies covered clinical research we’ve not been able to see people until very recently in our clinical research centers because of social distancing and these are of course very vulnerable groups so i think you know as we as we go through the early part of 2021 we’re all optimistic that we’re turning the corner at least with some of those restrictions being lifted but i think as a community we need to put some pressure on r d departments and and other sort of you know governance parts of the of the system to to start prioritizing uh alzheimer’s uh studies again and get them up and running as quickly as possible we’ve not been idle we’ve not been just waiting to get going again we’ve done a lot of work in terms of you know building registers and such like so hopefully when we do start we’ll start with a great deal of energy and success thank you craig chris well personally i’d like a covert vaccination so i can start international travel again and start attending these meetings in person but in the more serious answer is i’d really like to see us making progress towards introducing the blood biomarkers to improve screening and detection earlier about alzheimer’s disease so basically to assist recruitment as the number one name thank you do you want any further comments to ask here number one objective for 2021 is uh in the first half of next year get the gap epad network in place getting our first transatlantic clinical trial underway uh demonstrating uh what it takes to get a true transatlantic network put together and work with chris uh who by the way i have to as an aside lynn acknowledge that chris is live this morning and i think it’s what 3 am chris or something crazy so many many thanks uh but the third thing is uh i echo what chris and craig have said we must and we will start deploying biomarkers as part of our better characterization of participants and studies and as we work with our european colleagues and chris in australia that will be a priority and that does lead us on nicely john to discussion about the fire hermes project which is a biomarker project um isn’t that going to be a part of the gap european rollout yeah funny that transition was great lynn thank you uh i uh so gaap has initiated a study uh in uh collaboration with almost everyone on this uh lazad conference uh to do exactly what dr zerhuni and company were talking about which is uh to bring uh together i think we now have uh nine blood markers uh and uh four digital markers all being tested against centrally read beta amyloid uh pet images those uh data will also contain a complete sequencing of the gene it is our first effort to bring something that looks like real world evidence to what are the different platforms different technologies of blood and digital markers and how not just how they’re going to prognosticate the presence of amyloid but ease of use ability to deploy and uh we expect that study to start this late this month and early next uh but we plan to bring a phase two to europe feed it all into dr zerhuni over in the cohorts group um because we believe that markers can change every element of a trial design for the better thank you going back to some of the questions that we’re receiving and this one craig and chris in particular looking at the payer system do you think it’s going to affect the implementation of gaap in your geographies craig yeah i was looking at that and i could work out how it might and what was behind the question to be honest because to my mind the simple answer is no i i obviously you know gaap has been sent up in north america which is obviously not a publicly funded health system like the nhs in the uk but um certainly commercial clinical trials um you know the funding model wouldn’t really have any impact or any differential as far as i’m concerned with what we do in the nhs i think one thing i would say is i think is advantageous in some ways is that in certain you know parts of the nhs what we’re developing in scotland for instance is a sort of national register and that’s going to be funded by the national well hopefully funded by the national health service at a national level but i don’t think what gap does what i know the gap does would have any um any barriers to implementation in a publicly funded system but maybe i’m missing something by the question but i can’t think of anything to be honest and chris in australia similar answer for the commercial trials no for academic trials we do have some support from the federal government through their their grant to the australian dementia network which part of their part of the role the australian dimension network is to facilitate clinical trials so we’ve got some government support but the commercial income would more than take care of the gap requirements for commercial trials thank you going back to the live questions we’ve heard a lot great deal about the importance of recognizing the heterogeneity of human populations with alzheimer’s is there any thought of extending your platform beyond the caucasian populations into asian african and other countries and populations and john maybe you can start talking about the plans for gap and the expansion yes and i want to you know george is my partner and my chairman and my friend but i too want to join in complimenting them and once again and the team on a great luzon and one of the insights that came to me yesterday uh to answer this question is uh we will be effective we are committed to going to low and middle income countries and uh and bringing trials and research uh on the ground uh to various communities in those regions it is critically important we have blood markers validated for doing research in alzheimer’s trials because it’s not a lack of appetite on the part of gap it’s not a lack of appetite on the even on the part of sponsors uh to do studies there but there are more uh pet imaging machines in southern california than there are in most of canada combined just by way of example uh you can’t get likened in most low and middle income countries and you can’t get the imaging done so we have to be sure that we can conduct studies with markers that will then translate and do well as part of overall inclusion in studies we’re committed to that our timeline is probably a couple years out because the technology has to catch up uh but i think when their call for research uh and investment was made it was really a clarion call in addition to everything else in the way of infrastructure get the markers from prognostic to diagnostic to surrogate so that we can actually characterize patients and and enroll them in studies and know we have the same level of accuracy and lack of variability as the rest of the world and does the bayer hermes trial with all the nine biomarkers will those biomarkers be able to be utilized in the lower middle income countries do you think yes some definitely uh but they also right now our positioning on that under fda guidance would be their prognosticating biomarkers which will be very helpful but to have a really valid validated biomarker that could be in lieu of csf or pet is something that’s a few years off but very needed in my judgment so that we can broaden these studies globally thank you julian another question that’s come in again it’s very interesting a platform trails in your vision of clinical trial innovation and we really haven’t had them much in alzheimer’s maybe the dianne study is the closest we’ve come craig what are your thoughts here and then i’d like to ask chris how long have we gone um i i i of course i’m a uh absolute convert i believe the only way forward to do platform trials is always a huge disappointment with the kneepad program that we weren’t able to prosecute the platform trial which we had designed from everything from governance legal agreements you know you were part of it by cuba you know the the work that went into it the one thing that we just didn’t get across line was a compound to actually start the process but you know i think the the the argument for a platform trial in terms of cost efficiencies bayesian adaptive trials learning as you’re going through phase two rolling things seamlessly into phase three all of those arguments are still as valid now as they were five years ago when imi invested 64 million euros and setting up epad so i think the lessons learned from you’ve had have to somehow be um packaged up and shared so that when we do go back into doing platform trials and we may be overcome some of the hurdles that we we we didn’t foresee at the beginning of epad to make sure we go over around those more effectively but yeah the future i mean you’ve learned this from covid vaccine studies that the future has to be platform trials it’s a no-brainer chris do you agree with that yes i think i’m not entirely sure what the definition of a platform trial is um we certainly are attempting and have set up a national platform for screening to create trial ready cohorts and that that is paying off um it is helping uh speed recruitment for trials but i’d like we need to invest a bit more time and then increase the size of it uh and yes trials uh trial sites struggle for viability uh we know the problems the three years to recruit for a dementia trial if we have platforms in place this should greatly reduce the time and cost of running a dementia trial and lead us to effective therapies sooner i mean i think to chris’s point maybe very quickly definition in my mind the platform one where you have a single protocol and you can therefore share placebo i strongly support that thank you i don’t know how much time we’ve got left there’s a quick question which isn’t really quick where do you see the blood biomarkers being used gentlemen in the screening process or in a pre-screen maybe a pre-screen in a gp surgery um or a pre-screen out there in the community rather than at a neurology or clinical trial site what are your thoughts on that i’ll start with chris and then craig and john yeah i think it’ll be a staged introduction and eventually it will get into the gp to the primary care setting and so be a pre-pre screen but initially we’ve we’ve got to bring it into the screening sites and the specialist clinics uh so that we have pre-screened uh prior to head scanning established that it is a suitable replacement for pet scanning in terms of screening for trials which i’m fairly optimistic it will be and then as as we have access to it wider access and validation make it available for use in primary care to get earlier diagnosis and that’s another issue that we’ll address delayed diagnosis of patients often means they’re not suitable for trials so i’m particularly keen in using blood biomarkers for earlier more accurate diagnosis even in primary care to boost clinical trial recruitment thank you would you agree with that craig 100 and i think the what we eventually want to see how many months or years ahead will be you know gp’s doing an amyloid level and blood likely do a cholesterol level at the moment but i think as well as technology being there and the you know the knowledge about the accuracy the test etc i also think there’s that famous line that you know culture eats strategy for breakfast every day and i think what we need to do is bring on board gps and others to to really recognize that alzheimer’s disease is disease of midlife that express itself as dementia in late life until you make that sort of cultural clinical change people like primary care physicians are not going to be on boarded to doing a blood test for alzheimer’s disease and people at risk so there’s a bit of work to be done again health care readiness group can can be working on that at the same time as we develop the tests themselves for drug trials do you want any further comments uh lynn i only would add that i think we grossly underestimate the opportunity to use blood markers with practicing physicians to recruit for clinical trials there was a question about incorporating cares in the discussion more we saw some of this in the cove environment here in the states but we think it’s going to be a lot easier to talk to underrepresented populations and they’re treating physicians if the first introduction to a trial is a reasonably quick and non-threatening digital uh biomarker test or a blood draw things that they’re very accustomed to seeing the doctors are accustomed to ordering and interpreting and we are going to be actively working to make that the mechanism for bringing in practicing physicians to refer to trials because we’ll provide them with some data that will add to their practice and uh they’ll see that our approach is one that will benefit their patients okay we have two minutes left gentlemen so 30 seconds what would be your call to action for 2021 craig it’s i’m gonna sound like a broken record it is to really ensure that everybody walking into a clinic gets consented into clinical research thank you chris i love craigs number one i think i’ll go with it too i want to see research built into clinical practice much more than it currently is okay and john work with the team here to create the transatlantic network and then the australian and japanese networks so that as they consent them we can give participants a better experience of faster trial time and discover a cure thank you very much thank you very much everybody for participating for the questions that have come in and for listening to us
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Lausanne VII Day 3: Global Clinical Trial Support Platform

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