OK. Good morning, Good afternoon, depending on from which region you're calling in. I'm Hilda Fanaka had industry leaders, life science and healthcare at TCS and I'm very excited to be your host for this session on smart medication management and clinical trials. This is a topic that I'm extremely passionate about and also had the pleasure to drive several first of its kinds transformation. Any shelters in E label smart packages direct to patient supplies, both in my earlier roller changing a transcelerate and now at TCS. Next slide please. Now, I'm also thrilled to have three outstanding speakers and leaders with me today, which I know already for many years. As first speaker, we have Matt Moyer. Matt is a Director of Operation that supplied technologies at MSD and has 20 years of pharma experience of which 17 years at MSD. Matt has an in-depth expertise in analytic development, packaging and clinical supply operations and currently he needs the incorporation of innovative clinical supply technologies at MSD. Matt also previously led the Transcelerate Patient Technology Initiative and is a certified Project Management Professional as a Bachelor of Science and Chemistry and a Master of Science in Pharmaceutics and an MBA. A second speaker we have Umbro. Umbro is a business development manager, medication adherence monitoring solutions at Shrine and Medi Pharm. Who leads the development of new markets and printed electronic solutions for pharma? And he has held many leadership positions in sales, product management and business development for the pharmaceutical as well as the automation industry. And he has been for Shriner for more than 28 years and he has a degree in printed technology. And a store speaker we have Doctor Paul Ingram. Paul joined TCS only end of April 2 months ago as industry leader for TCS AD supply management and he brings with him a wealth of expertise of 25 years in the pharmaceutical and medical device environment. And he has an intensive no hope in clinical supplies which he has built up at various organizations such as phase one manufacturing. Units and the first trial supply service companies like Fishers and Catalans. And his recent focus was on establishing innovative and strategic solutions within the clinical trial supply chain both for decentralized and patient centric trials. And Paul has a PhD in pharmaceutical development. And finally, I'm Hilda Vinaka and I joined TCS now nearly two years ago after being for more than 25 years at the pharmacy. Right, where I held several leadership role in pre clinical and clinical departments and had the pleasure to shape and drive several Mission Impossible programs to successful implementation through collaboration. And at the left side, you see our very ambitious agenda for today. First, I will give a short introduction in medication management and clinical trials. Next met will dive into depth in digitally enabled trials with some real life use cases. Umbro will then introduce us in the smart mitigation package world and Powell will end with guiding us in how adopting a flexible, personalized and real time mitigation model and we end with some key takeaways. Now quickly prior to starting let me give also some housekeeping rules. You can access this webinar using phone, tablet, portal or any device. If you experience any connectivity issues, please refresh your links and the preference is to use Chrome. After each topic we will have a short Q&A session and you can ask your questions by using the chat box with the question mark that you can see at the right top of your screen next to the leave button. And in case your questions cannot be answered during the session, we will respond to it offline. And lastly, this session is recorded and the link to the recorded version will be sent to you after this session. OK, so let's get started and let's move to the next slide, please. So let me set the stage by highlighting some of the challenges in medication management and how smart medication management can be a solution. Next slide please. So I clustered the medication challenges in two big categories. So at the left side we see all challenges linked with patient appearance, for example, unclear and complex dosing instructions limited to no personal support at home, lack of motivational support of patients simply forgetting to take their medication. And as we all know, medications do not work if you don't take them. Studies have also shown that adherence rates can decrease with 40% after one years. No, not Terrence can result in suboptimal effects, more side effects, and lead to incorrect assessment and conclusions for the investigation product by the side by the sponsor. And at the right side of the slide you see some challenges in the mediigation process. There are many stakeholders and siloed systems involved, lot of manual paper based processes. We have limited or fragmented oversight of what is happening with the supplies, medication is prepared that studies specific level labeling as well as temperature out of range. Those processes are very labor intensive and so on and as a result through accountability. Is really one of the top five inspection findings. Also up to 25% of on site monitoring activities is linked with investigational product activities and supply waste is very high. On average around 20 to 40% of prepared clinical supplies never reach the patients. So a lot of challenges but a lot of opportunities and here's smart medication can often the solution. So next slide. Please. So first of all, with smart medication we can provide personalized and tailored patient support. Secondly, we can also create integrated medication ecosystems and lastly, we can establish flexible medication processes in line with the needs of the patients in the clinical sites. And this all by combining technology and creating partnerships between the different stakeholders involved such as the CMO's, the depos, the distributors, couriers, RTS, MIT suppliers and so on. And that is exactly what Matt and Paul will address in this session today. And with this, I would like to hand over to Matz and let's move to the next slide where Matt will give us insight in the digitally enabled clinical trials. So Matt, the floor is yours. Hey, thanks for the introduction, Hilda, and the opportunity to speak here today. You could go to the next slide. So I want to share a couple of thoughts around digitally enabled clinical trials, but I want to start with a foundation, which is culture, right. And if any of you have heard that the saying before, the culture eats strategy for breakfast. And So what that means is that despite the best laid strategy for the development and deployment of these technologies and trials, if you don't have an underpinning culture that believes in the technology and believes in the opportunities that exist, you won't go anywhere. And so I want to start with. Culture and use a few illustrations to do that. So the first one in the upper left shows the clear connection or the need for a clear connection between the idea or concept of these technologies, the underlying business strategy and then the return that's expected from the deployment of these technologies. So you have a clear need to be able to articulate that very well to stakeholders in order to begin to build their confidence in the ability to recognize why we're doing this and what the ultimate. Benefit outcome will be for all the stakeholders in the trial ecosystem, whether it's the pharma company itself, whether it's a clinical site or whether it's our patients. We then take the concept and move it into a piloting phase. You see on the bottom left that's intended to represent where we really look to begin to in a very structured way, test out the technology in a very controlled setting without impact to ongoing trial to make sure that it works as intended, it delivers the data that we intend it to and that. That data can be integrated into the ecosystem of the company in question. Recognize too, on the middle, center, top that change is possible. And this is back to recognizing that they're articulating to folks that we have done things this way a certain way before, but we can very much change that it it's possible to change. And honestly, there's a lot of value and change. And so you'd be surprised how often that people get stuck on just the idea that we're we do things the same way again and again. Has a really foundational need to ensure that we address the willingness for change. Bottom middle is knowledge management. So as you begin to pilot these technologies and these approaches, ensure that you're capturing that foundational knowledge so that it can be replicated and used again in the future by others who are trained on the process. You know foundational knowledge is only useful if it's disseminated across the broader organization and knowledge management. The key to doing that and then finally and perhaps the biggest one and reflected so on the slide is the fact that the patient needs to be in the center of what we do and the patient carries the loudest voice here. So if we all align in the development and deployment of technologies that benefit most the patient and their participation in our trials, it makes everything else a whole lot easier. Next slide. So if we've moved beyond culture and now look at strategy, we in internal at MSD have really kind of used the two prongs of pronged approach. One is those the pilot that I mentioned, the technology development trials which you see on the top and these are small scale with the technologies of interest. They're intended to test readiness for us to use the technology in our larger scale like face clinical trials that can act as capability build builds, they work as a learner and confirm paradigm. In a fairly rapid fashion, test and deploy the technology, learn from it and decide whether it's viable to move to the next step. And they're most often program agnostic. They're not typically tend to do a program that we may opportunistically use it in one of our phase one programs. We then shifted the portfolio facing opportunities and these are specifically aligned against the targeted business need and a targeted molecule whether it's to a rich data sets for program decisions, improved trial logistics and efficiencies or used as an opportunity to proactively engage with regulators. And we do that through you know type C meetings say for example with an ID where we specifically lay out the technology that we're intending to use and the why for the regulator to seek feedback. Next slide. So now having shifted away from culture and strategy, I wanted to do a little bit of a deep dive into a technology area of interest for us and then some examples of pilot deployment of that technology that may be of interest to the group here. And so it hears technologies that are actually my primary area of focus, recognizing that the old way of measuring patient adherence much like Hilda mentioned is has an awful lot of deficiencies, whether it's internal bias because. Relying on patients self reported and the patient wants to appear adherent or whether it's the lack of contextual data in the event of using pill count to determine whether a patient dosed over the entire regimen. These are both very inadequate ways to measure adherence. And so we want to shift to moving to moving to technologies that allow us either at you know time date stamp when the patient interacts with the package in the case of smart packaging or an app based technology that allows us to. The filming or the recording of a patient dosing as a means to understand what actually happened and did they digest the medication at the right time, in the right way and the right quantity per protocol. So these are a few examples to show you categories of technologies. We tend to center our efforts in the smart packaging and photographic documentation effort, but there may be other reasons to pursue the other technologies as well. Next slide. And so if we take in particular this is the pilot trial run in 2016, this has been published. So you could actually find this live in image journal. But what we did was take the smart blister that was used in the study and compared it to other sources of adherence data in the trial in E Diaries listed. We also took PK samples here and so we used that as a point of comparison to and this was a QD or once daily 14 subjects. Two weeks worth of dosing, so pretty simple. One clinical site in 13 of the 14 subjects performed very well and more or less as expected. Hard to see the detail, but the shift in the dots really just represent some level of variability in terms of dissing time for the day. We had one very interesting actor in the trial who took days, took doses when or expressed doses from the package when they didn't say that they did and there were a number of timestamps at the very end of the trial. About 1/2 an hour before the patient returned to clinic, showing that they popped the last few tablets out of the blister right before they returned to the clinic as opposed to dosing as we expected them to. And this was reflected in their PK. So this confirmed what we knew already as part of an infrequent PK sampling and that's dissing didn't occur as intended. You also see on the right, we did a subject questionnaire and received very positive feedback about the willingness to use the smart package in the future. It was really minimally burdensome. For the patient. And so it's a technology that we now use in several of our trials. Next slide. Another example of types of technology is the digitally enabled trust platform. Now this isn't an internal concept that we've termed this, but it is essentially the platform concept where you can plug and play multiple devices into a single layer of integration and that layer also has mobile app development capability. The data from that platform then feeds into an internal data lake for analytics. It may feed into your clinical data repository. It would provide a real time dashboard and provide an opportunity for patient engagement via the app as well. And we see this as an opportunity and a necessity for trials in the future, especially those that have multiple digital inputs. So next slide. So a single example of deployment of using the digitally enabled cross-platform, we leveraged the TCSD connected clinical trials platform. It allowed us to collect Bluetooth data from one of our adherence devices. So this wasn't just a smart question, this is actually a medical device allowed us to be able to transfer that data actively or passively into the platform, allowed for visualization of that data in real time and reporting of non adherent circumstances if a patient forgot to dose. It allowed us to send reminders providers the opportunity for data storage and download and supported a BYOD or bring your own device paradigm where it simply required participants in the trial to download the app onto their own device and use it in the same way that somebody that would be provisioned device would use it. Feedback from the study was positive and it also helped us clarify expectations for what falls into the study specific configuration versus the general configuration for the platform bucket and what kind of timelines are we talking about. From a development deployment and update a process. These are all very important internal questions as we begin to overlay the technology approach to the standard clinical trial development approach. Next slide. So just want to end with a few key takeaways and consideration. Certainly letting the business drive the need is important. We are not a hammer looking for a nail. We instead identify areas or challenges that our clinical trial teams are facing and look to leverage technology to support those. We leverage pilots to gap assess and obtain stakeholder feedback we need to create the process. Again, that's that knowledge management piece so that anyone can repeat what we're doing here and that we're all very clear on timelines. Responsibilities, deliverables and everything that goes into execution. We want to create an opt out mentality in that these technologies become the standard and you need to rationalize why you would not use them as opposed to the other way around. That's a future state desire, certainly not A1 size fits all approach. Certainly we need to demonstrate return on investment that's linking to the business strategy and that return I showed at the beginning and then finally data privacy and security are core considerations as well. And so with that, you can move to the next slide and I think we might have a moment or two for questions. Thank you very much Matt for this very engaging and interesting insights. And it's clear if I see also of the questions which are coming in from the audience that also the audience really enjoyed your talk. So let me otherwise take or start with the very practical but maybe also a generic question that came in and it is what has been the biggest challenge to date in implementing these technologies in clinical trials. Would you mind giving your insight into this? Absolutely, yes. And I think it goes back to my very first slide and why I decided to kick off with culture because we started with a very. Grassroots effort and there were folks, myself included, doing this on a on a very part time basis in addition to our standard job. And we really, it really took us a while to get moving because we really did have to shift the company's culture from a very, I'll say a relatively conservative approach. And you know things are working well. Why do we want to change things They're working well in into understanding the possibilities that exist with these digital tools. And that was not a quick. Process that would lead to quite a bit of time, intensive effort and discussions with the working level, with the, with senior leadership and with many others. So I would say that was the biggest challenge. It was the shifting the company's culture to embrace the new technologies. OK, thanks. Thanks a lot for this answer, Matt. A second one and that's really focusing on the smart packages and a little bit also maybe link with your experience on patient technologies. Overall using smart packages, we have much more insight and more data than ever before and also real time. But how can we ensure that sites are sponsors like you for example, are not becoming overwhelmed with all those? Type of data. So do you have any advice for your colleagues on the call now on how to handle this huge amount of data? And smart packaging I think provides it's more data. It's not perhaps an overwhelming amount of data that like a real time continuous sampling wearable might provide I think. But regardless of whether it's smart package or wearable or other device, it's really about having a very clear. And aligned data analysis plan. So what are we intending to get from a data perspective? What are we intending to do with that data? Where does it need to go? Who needs to see it, what decisions are we using it to make and things of that nature. So having that clear alignment up front and then having the structure, the digital structure to support that analysis plan, I think it is the most critical piece. Very, very interesting and. We have still some time, so let me still ask one other question. This is about health authority submissions. You also address shortly about regulatory question is also related to those kinds of smart packages. Do they require any specific health authority submission preparations and also order medical devices? Is the app that you can use the mobile medical appliance phone? Can you give some insight into this? I would say still actively discussing maybe a number of these points because I think there are many nuances to it. If you just think about a smart package in substitute for a standard package in a clinical trial and having the site, the clinical site reading and interacting with that data and counseling the patient on adherence and maybe even sending them reminders via via connected app, We don't view these as medical devices. We do recognize that the technology we do. Reference the technology in the clinical protocol because we have an intention of using that data as source data for adherence in our trial. But we don't believe these are medical devices or meet the need meet the threshold or requirement for a medical device. Now there may be some things that drive that differently. There are digital therapeutics that are intended to be more proactive with the engagement and adjustment of patients on therapy, but at least as a. As it relates to smart package, use. Pretty straightforward smart packages and clinical trial. We don't see these as medical devices. Kiddo. OK, thanks. Thank you very much. There are also few other questions still in that for being safe for the time also to allow Poland to do their story. I suggest that we answer those ones offline. So with this can maybe move to the next slide and where we will also hand over to who will start to introduce us in the smart mitigation packages for? Clinical trials world we work, the floor is yours. OK, so thank you for your introduction. So I'm very pleased to be part of this webinar organized by TCS and happy to give you an insight about the sensing technologies, which let's say over the last years are more and more used for medication packages. So these SMART solutions are supporting improving outcomes of clinical trials and the possibilities of combining such technologies is in the meantime quite broad. So I will use my presentation. And to focus on the most relevant and hopefully attractive ones. Next slide, please. So before we step in some use cases, you can see here an overview how smart packaging is selected into two main sections. So this is on one side left, the intelligent packaging which covers the whole portfolio of smart devices and smart packages which deliver enhanced functionalities. So it allows to gather data insights along the journey of the product and create. A secure two way communication pathway between patients and healthcare professionals and of course potential other stakeholders. So the technologies are also being more and more used in desert utilized clinical trials. The other field is active packaging, so they added value of packages here to provide end to end visibility in complex global supply chains, stop criminal networks from exploiting weak points. So under counterfeiting features are an example and offer also an improved patient experience. So now let's have a deeper look on the topic of smart packages. So next slide please. So here you can see that currently sensors could be integrated in a wide range of typical medication containers, forms and designs and so there are solutions available which are adopted into primary packages. Sometimes it's technical feasible to have it also and then secondary package integrated. So the relevant criteria of course technical feasibilities, production process, usability, and of course specific use cases with dedicated needs and expected outcomes. So you here examples of the most valuable areas of using such sensing technologies and for example intake and dosing tracking. Temperature monitoring as well as monitoring of other environmental conditions. So this all these feasible and I will focus now on the topic of interference monitoring and what aspects you should consider for such a smart package. Next slide please. So in case of starting a small packaging project, there are several areas to be considered. Yeah, and you see here a lot of different fields which should be clarified within a dedicated project team. And I also saw that some aspects showed here were also highlighted during math sessions. Matthew, you say culture. I think that's a key success point to get assessed 6 successful project. So often such project needs to establish new technology. To align and manage data flows, to communicate transparently between all stakeholders, and to define a best suitable supply chain. And to prepare is this the first time to go? To prepare the go live very well and comprehensively? Finally, in our experience, one key success factor is to establish a good and trustful relationship between all stakeholders to achieve finally also a trustful, open and goal orientated work. OK. So let's take the next slide. So now the example of a smart medication package for blister medication enables adherence monitoring. This hybrid electronics you see here a bit seamlessly integrated into cotton wallets which are used also for normal clinical trial packaging. And when you're patient? So that's the functionality. The main functionality is when a patient pushes a pill out of the cavity at the same time, the data is generated and stored at the chip automatically. The tears started the timestamp of this event, plus the precise dosing of which and how many pills are taken. So the maximum amount of cavities which can be tracked as currently 64 cavities based on our resolution and also scanning or reading of the data from the smart package could be done via NFC, Near Field Communication kind of RFID technology or alternatively with other transmitting technologies like Bluetooth or GSM. So in regard to NFC, of course there are different use cases and always a question, what is the best technology to transmit data And you have really to look into a specific use case, what is the best one. So there's no, let's say the best one. You have to balance it. But we see here for this kind of use case, NFC is the most valuable one. And NFC I think most of us. Now in the meantime, the wireless payment for its actions while banking or credit cards he also NFC tags are integrated in the card and the scanning process will be initiated by tapping a reader or smartphone closely to a smart package. So that's easily in one second. Performed. OK. Next slide. So here you can see a selection of. Different kind of wallets maybe? You step back to the other slide. Thank you not only to see that. Maybe all these kind of different kind of wallet designs used for clinical trials, so they are most of it child resistant and others are foldable wallets. So principally in all of these designs the electronic is in the meantime very tiny and could be integrated seamlessly. OK. Next slide. So here you see the main components which are integrated in a carton wallet. So these are conductive traces, so conductive lines which go over each cavity and then finally they are bonded to a printed circuit board PCB which have the chip on and the that's the brain of the complete smart package. And at the end, this will be marriage into kind of assembling of this Cardon wallet. So finally you will get a small crystal wallet, which then will be further packed in a further process which we will see at a later stage. OK, so next slide. Please. Yeah. And I think this slide is showing the process and process of manufacturing a small blister ballet to give you this inside. So of course, electronics is a part, which is very important and the other component is wallet. And then all the components are assembled together at the end. The final package assembly will happen at a farmer site or at a CMO which is combining the primary blister pack into the smart blister wallet. So at the end this when it's. Packed completely. Then it goes to the clinic sites. So you see also that the electronic and all the functionalities are ensured to be functional. And therefore at the beginning saying here beginning starting with the electronics and then the manufacturing process of the Smart Pistol wallet and finally also add a final blister assembly site. These scanning, verifying and configuration checks are done over the whole supply chain or manufacturing supply chain and to ensure 100% functionality so. There are also possibilities to program additional data on the package to add for example digital track and trace system by considering for example batch numbers for each production step. OK. Next slide please. So here I like to give you an example for first clinical supply of such Smart Vista Wallets. So and typically there are upfront some milestones to be considered and it always starts with the initial design alignment for the blister. And the wallet design with the integrated electronic. So I think we should. Step back to the other slide. Please. Yes, so when the design alignment is finalized. Always the first sample production follows to give the manufacturers, pharmacy, emo, sponsor and so on and of course other stakeholders the opportunity to verify all related steps And also with this final design freeze at the end the production can then be started for the whole requested quantity of a dedicated clinical trial. And of course to get a first touch and feel and for these technologies and functionalities there are often sample kits available as also Shrine also offers a kind of demo kit in order to run kind of proof of concept and of course within a shorter timeline and of course at the beginning with less efforts on all sides. OK. Next slide please. So. Discharge is showing you a typical process flow of a smart package within clinical trials. So first of all Pharma or CMO is preparing or finalizing the smart education pack to IMP kit with all relevant data such like kit number, expiry date, randomized number, serial IDs you can put on the chip of the package. Then I think it goes to the clinic site and here the handover of the kit to a dedicated patient will take place. So finally the patients will take their medication and can read the utterance Tyler via smartphone app or of course they can bring the package back to the clinic side where then the package will be scanned and the data will be read out. So both ways are possible, but in case you give a patient an app, I think you should consider several aspects for a smooth usage without any complications. So of course I think valuable is to give them instructions up front and maybe to combine it with other services. This will definitely help for a smooth run of such clinical trial with smart packages. OK. Next slide please. So what is the value or what are the benefits to have such experience data available? Of course there are for each specific drug development a lot of scientific values in to compare vital data with reliable insurance data. So only the flagging of patients with such materials data seems a benefit to analyze vital data in relation to a specific adherence level. So obviously there are robust outcomes here in this business case for clinical trials. Which are reflected in having also high efficiency. So let's say in a best case you can eliminate monitoring visits or on site activities. So here the possibility is that one person study project leader can have a dashboard like TCS is providing to see all the data of each clinic of each patient and can monitor it. Overall for the whole study and give feedbacks. In real time. So that's really a high benefit at the end. I think it's also improving the timeline of clinical trials to get hopefully an approval of a new truck earlier. And at the end, we saw it also pushed by COVID situation that decentralized trials are more and more used and I think this technology is also supporting this decentralized trials as well adaptive trial designs. And if you're more flexibility. OK. Next slide, last slide which. Now I like beside the tyrants like to introduce one another use case in regard to temperature monitoring and how it can be managed with two different technical solutions. So the other demonstrated way of temperature measuring requires RFID tag on medication containers which will be scanned via off the shelf handheld scanners. It each scanning event temperature data is generated here and finally the benefit. This year that multiple units can be scanned by one scanning event, so finally it's a more cost efficient solution without having a battery inside. So a battery is requested for the alternative use case below, having a real monitoring solution which records the temperature over the whole supply chain continuously. And the chip could be programmed to measure for example temperature for all 30 minutes. And at the end of the NFC tech on the medication container allow us to read out the complete generated data and to update it whenever it's needed. So finally, I'm at the end and hopefully my presentation gives you a better insight about smart packaging and some related topics. So thank you and now I'm open for questions. Thanks you for this very interesting and also learning full insights in smart medication package. You're really a very detailed which is extremely nice about what is about which benefits, values, which items did take into account etcetera. And I think also the audience raised quite some questions. So let me start here with the first one which is honestly a very practical. My thing also could be a little bit of technical one. The question is there a continuous radiofrequency sun by the smart package? Yeah, good question though in case of using NFC. The radio frequency you have only when you scan the SMART package. So there's no continuous radio frequency if you compare it to Bluetooth or GSM. So NFC is only transmitting data and having some lower frequency. The short time when I say OK, you need one second for tapping and reading out a package. OK, thanks. Thanks. And here also it's clearly we have some smart package experts I think also in the audience and this is about the shelf life. How long is the shelf life of the smart package and what in case the battery is empty or we then do we loosen all the data? Would you mind giving some more insight into that question? Yeah, surely said. I'll fly for the service life of a battery. So I said battery. So the power source is key for the shelf life and normally we say three years after activation at AC Moore package site that's I think are reliable data we specify at the end. I think in a worst case you asking when a battery is empty, I think all the generated data during cleaning. Clinical trial. If this data is stored in the battery is empty. You can read out the data by using the readers and these data are still available. OK, good to know. And maybe a last question and then we will move over to Paul. This is from a patient perspective. On one hand, is there any difference in usability between a traditional package versus a smart package? So first answer would be should be. No difference. Because you when a patient is not using an app, only taking medication from a blister pack, then the usage is the same if you have a non smart or smart blister wallet. Of course when it comes to using an app via patient then some other considerations have to discuss. OK. Thanks for this answer and I think we need to handle the rest of the questions also offline. So let's now move to the next slide and hand over to both for the last session and where he will introduce us in adopting a flexible personalized real time mitigation model, both flourishes yours. Thank you, Elda. Extra then please. So. I'm going to give some real world examples of those flexible, personalized and real time medication management options, but I just wanted to reflect that we've seen from Matt and Nuvi that patient adherence can be achieved with smart packages and the change management process in order to bring them into the supply chains. But beyond those smart packages, there are other things that we can do to ensure that. With platforms and available to techno, other technologies, personalized and tailored patient support is available that there's flexible medication management processes and we can use them through an integrated medication ecosystem. And I'll give you some examples as we go on about how those technologies and partnerships can come together and offer alternative and supplementary solutions. With small packages. Next slide please. So. Understanding that, Matt reflected about the know an orthodox limitation of apps and Diaries that they're still a place where they can capture data if there aren't smart packages or actually they couldn't supplement and complement a smart package scan from that app. So here we see the ability to link the medication regimes for a trial closely to. The note, the notifications on the left that appear on a patient's health device, bringing your own device, and that enables us to then get closer to actually the treatment regime of choice. We're not just telling them in the old way it's time for your medication, we're now starting to edge towards what they need to take. And how they need to take it so this is 2 tablets one hour prior to their food intake. OK, that notification can then be clicked and automatically prompt a diary entry. And if the diary entries on their smart device is linked to a smart pack reading in real time, there's auto population available as to what was actually removed from the pack to confirm that they've been tested it. And knowledge can they complement each other? The other things that can also happen is you leave it editable so that the patient themselves confirm what they did take and consume rather than what they removed from a pack. Or you can have auto population by just a timing, so when the diary entry opened that auto populates was that the time that they actually took the drugs and have that editable backwards. It also gives you the ability to ask other questions. Such as did you take your medication here one hour before a meal as prompted? Because when the notification comes up and when the diary entry is completed, maybe a separate times, OK? This then allows us to get very, very tailored towards the medication regime. Looking at their adherence and their compliance and then drive some engagement of the patient to take their medications correctly in an alternative way. OK. Next slide please. What this slide example is here to show is that beyond just a patient engagement directly through an app and to drive adherence, we can also offer them support. So when medication isn't being taken correctly or there's a there's a problem, there's alerts through the notifications and in this case, if there's a missed dose and the reason for that missed dose is for a medical reason, alerts. Can be sent around the ecosystem so that there's through a site portal, there's a notification to the site staff that they can evaluate what's going right and wrong and make their decision to intervene, support that patient so they continue to remain compliant where they can, or at least engaged and supported so they don't drop off the study. Again, this is around real time interaction and insight into knowing what's going on with the medication and making real time decisions to ensure that the data is in, the integrity of the data is maintained. OK, next slide please. Of course, one of the great things about capturing that through an app is that you can help the patients help themselves. So through that intake compliance, through the diary, you can give indications of how the patients doing for themselves so they can make an informed decisions. Do they, do they need to do something differently or are they on the good path? This is taken from real time data from their compliance of their medication. We can set the thresholds for where the different red, amber, green categorizations are. Of course automatic and notifications can be sent if the compliance drops to a certain level to other stakeholders within the ecosystem to intervene if required. OK. Next slide please. And this is probably the most interesting sort of forward-looking. Concept of the enabler, we're in the still in the personalized and tailored solutions, but really patients want to have things as simple as possible. And whilst we know that paper based labels on the products are a regulatory requirement, the movement towards digital labels available through patient apps is really driving forward the engagement of patients who can get the label downloaded. Unavailable online and offline thereafter. That tells them in a much more engaging way what they need to do in local language, the zoomable and scrollable. And in this case, and as shown, can actually then ask them to confirm that they've read the and understood the instruction, which through different groups. In the past, especially ISP, we've seen lots of reports that patients don't read their labels, font sizes are too small, and especially with booklet labels, they're often returned unopened, which is highly suspicious of them not being read at all. OK. That's it. So next slide then please. Sorry. If we look towards a more flexible medication support tool, this example really goes to lend itself to the decentralized trials. OK, an app in the hands of a patient that can scan, verify kit numbers. Allows them to receive direct to patient at home shipments, but not just have the Courier confirmed that it's been delivered, but have the patient confirm. Through automatic scanning. Or manual data entry as a backup that they have received the correct kit. And of course from what we've seen previously that could then trigger an E label or. A digital label being pushed to their phone. It could then start the notifications and the medication Diaries specific to their dose regime. OK. It could also then push a new label through to their phone if it's different from the previous dose kit that they would have if they were on a titration study for instance or in an ascending dose study, OK. This then really starts to allow us to understand in real time as well through the ecosystem. The site would be then knowledgeable that kit is available and that patient has started their dose. That integration through to RTMS is then possible so that the complete supply chain is aware of the same information in real time. OK. Next slide then, please. This is coming towards the end of my slides, but I really wanted to show this one in the It's not all about the Patient app, so this is the site portal available to the clinicians. Probably more relevant, not necessarily in decentralised trials, but obviously much more. It gives them greater visibility of what's going on when it's not at all in their shop. So here you see real time insight available to the medication intake data, the health surveys and the label confirmations that have happened in the top and then the bottom. They're the clinicians and the clinical team are able to see real time blinded dispensing, loss and damage reports, the returns. Being managed and they're able to some extent to manage the dispensing and delaying and skipping of doses should there be dispensing and delaying and skipping of doses should there be adverse events. This really goes to look at how the whole trial from end to end has become much more personalized and tailored to those individual patient needs, but then allowing the data to be fed around the ecosystem so that all the stakeholders can be maximized, the use of that data, which brings me on to my last slide. So next slide then please. And this is important. We've moved towards that integrated ecosystem segment. But I really wanted to highlight here that with within those joined up systems, IT access control is pivotal to ensuring that in the joined up ecosystem is strong and robust and secure. OK. So in this example you've shown that. By having patient confidential information to the subject ID captured where an A patient name and their address is captured either at east consent, automatically uploaded into a database or manually updated if it's not a consent. The reports that can come from that. In a system. So I am required to deliver direct to patient home. Our only access requirement of the career. And within and in this example, you see that the Medication Shipment Address report is available to download as an excel or PDF, but the access control is to the career only and that is so that a depot. Or a sponsor access who do not need to see that patient confidential information is not given. OK. So that really then comes to summarize how through those three separate areas you can address? The individual needs and tailor the needs of a patient. To really deliver, I customize. Engaging and compliant. Solution. And then I just left the next slide and answer some Q&A. OK. Thank. Thank you so much Paul for this and it's very encouraging on one hand to see what is all possible. Again audience was very interested in all several questions. I know that we maybe don't have so much time, but let's still go for a few questions, very concrete form that they asked here, they indicated you talked about a lot personalized. Patient support, which was absolutely very interesting to see, but do you have also any feedback of patients maybe from your studies what they liked or not liked? It's interesting. Was not compliant on its own that. The digital label is a is a key game changer on that device for patients to have access to it, to engage with it and feel confident about it. They seem to with studies that have run for greater than six months in elderly patients in Asia, we we've seen the greater than 80% intake compliance and they mainly atone that to the fact that they had the access. To the label that was so much more in easy to interact with than a printed label on the product. OK. Thanks. Thanks a lot. And maybe one other because this I also find the very interesting question and with systems and devices be integrated and anything that you can share with whether it has also an impact on the quality of the data from the studies that were performed. Yeah, so there's there are a number of examples that really go to this. So obviously you're digitalizing your electronically verifying. A lot of the chain of custody, chain of identity, the reconciliation of drug at the end is a lot easier, especially with smart packages. We've also seen that a number of let's call it dispensing or assignment issues where a site goes to give a patient a kit, but then actually would have recorded it and RSM is correct, but because the patient has scanned that pack, it's found to be the wrong kit because of they pulled the wrong one off the shelf we've seen. Studies where the global studies where RSM has controlled the study but the apps and the scanning have caught 10 errors of kit selection compared to what the RTSM said in a month. Very, very interesting. Thanks. And we have now come to the end of our session. So let's maybe move to the next slide and also let me summarize some of the key takeaways. So let's move to the next slide. First of all, there are many internal and external engagement stakeholders involved and we would really highly recommend engage all stakeholders early and along the way. The second core item which was also highlighted by Matt. Do not underestimate the change management aspect and Evan also say take a stepwise approach start small and big and where he use as a very nice example one that he's ready to use started demo kit for small packages and we're honestly people can easily get familiar and experience and what or now exactly. The benefits of smart packages and so on and how to use it also all the speakers on one hand that says it's not an all size of 1 size fits all approach can differ depending on the compound indication, the study face, patient populations and so on that one smart medication management tool can be more appropriate fascists another one and that's where Paul also went into the flexible mitigation processes which site can for example modify. Treatment, if the medication needs to be sent directly to the patient, OK, it can be done like that etcetera and really or that endpoint there. We really believe also smart medication package or tools can be a game changer and we hope that you are ready to join us in this journey. So if we go to the next slide because we're really at the end of the session, we want to have a big thank you to Matt Yuan and both for sharing their. Experience and also to the audience honestly for all their questions. In case we could not answer all your questions during the session, feel free to contact us or send us an e-mail and about the session where you still have questions about. As already mentioned, the recorded version will be shared with you after this session and on behalf of TCS and all speakers, I really would like to thank you for joining and honestly, good luck for making honestly the impossible possible feel smart technologies and partnership, Thank you very much.