The Five Biggest Stumbling Blocks Small Device Teams Hit in Study Start-Up and What to Do Next

Hi.

Unmute myself. Good morning, Rob. Afternoon.

Hi, Sean. How are you?

I'm well, how are you?

Yeah, very well. Well, thank you. Good. Where are you based?

Just outside of Philadelphia. Where are you?

Based in the UK, on the south coast of England, a place called Brighton.

Oh, okay. Very nice. I've heard of Brighton. I've never been there.

Yeah, it's lovely.

That's where British people go on vacation.

It is, historically, yes, yes, a holiday destination for British people. I think they tend to, go to Spain now, but, yeah, historically it was, Yeah, holiday destination.

Spain is nice, too. Yeah, there were, when I was in Malaga, there were a lot of British people there.

That's funny, I'd just moved back from Malaga. I lived in Malaga for two and a half years, and I've just moved back to the UK in the past week. So, yeah, lots of British people there as well.

Very nice. Did you enjoy living there?

I did, I did, yes. And I moved at the worst possible time. I moved from the most beautiful time in Malaga, when it's like autumn, when it's… the weather's bearable and not too hot, and I'm now in England, where it's dark and cold and grey and wet. So, yeah, it's been a big shock to the system.

And Laura, tell us where you're based these days.

In Barcelona, yeah. So, not so grey. As the UK. It's quite nice here, and not as warm as in Malaga, so that's, good balance, I would say.

Well… Barcelona is a great city, Malaga's a great city place. And, so, yeah, those… those are both… I like, I like Spain. And those who know me on this call know that I also love Italy, it's my second home. is…

I believe.

I spend… a lot of time in Rome. In southern Italy. So…

That's nice. Do you travel back to Europe, a lot?

Sean. I think I was in Europe 6 times this year. Okay.

Oh, well.

And was, like, not… I don't want to travel anymore this year. I'm tired of traveling.

Yeah.

diarrhea's all.

Huh? I like it, and then I don't like it.

Yeah, I also think the idea of traveling is often more romantic than the actual doing of the traveling. Like, you think, oh, I've got these conferences in all these far-flung places, you think, oh, wow, how exciting. But when you're in the airport and you're eating another airport meal, the reality… doesn't necessarily live up to the, the dream that you had when you booked all these conference tickets and stuff. So, yeah, sometimes good to just be at home for a while.

True.

So… We're gonna get started in a minute. People are still joining, and so I sort of wanted… to, you know, take the time before the call to invite any of the attendees to join. Francesco, if you wanna… Someone's at… Kim Servants is having audio problems. So, anybody that would like to be promoted to panelists, just raise your hand, or, feel free to decline, as well. And, I won. So, I met Laura and Rob very recently. they had seen, I guess, the course that we were doing with Donoa, about, Pre-market.

clinical studies in the EU, and I would encourage anybody that hasn't seen the 5-day email course to take a look at it, because this is one of the new sort of product services that we're developing is this idea of, you know, how do you transform I mean, everybody on this call has essentially the same problem, which is, you know, how do we get more clients? I have this problem, everyone on the call has this problem. How do I get more clients, and how do I get more clients in 2025 and 2026? And the goalpost keeps moving, thanks to AI, thanks to a lot of things that are making…

Expertise seem optional, right?

Hmm.

And, it's really not. And also, when it comes down to people just sort of rolling up their sleeves and doing the work. like contract research organizations, like contract manufacturing organizations, like biocompatibility testing or cybersecurity. You know, these are the kinds of people who are on this call. These are the kinds of people and the products and services that they offer. So one thing that I would invite you guys to think about and to discuss with me offline is we move forward into 2026. Is how do we create a network of partners that feeds each other business, because obviously a manufacturer is not doing the contract research and vice versa, or the human factors testing, or the this, or the that, right? And so we have a lot of specialists on this call, so how do we, bring that together into a meaningful network and create an ecosystem that serves the members? And this is…

you know, something that we've been trying to do in MedTech Leading Voice Exchange, and… been welcoming, new speakers on the Friday call, introducing them, and letting people, ask questions and become familiar. And so, with that in mind, I would like to turn it over to Laura and Rob, and ask them to just tell us who they are. You know, where they come from, and how they arrived at, you know, their newly founded contractor research organization.

Thank you, Sean. Rob, do you want to share your screen, or shall I go ahead? Because obviously, we prepared some slides. We cannot do without slides. I think it's part of the industry in some kind of way.

But I know, Sean, you did say that, this should try and be a more of a discussion-focused, events, so we'll… we'll try and focus more on the discussion than… than rely on the slides, but, yeah, we just put something together just to, have a guide for us. So, yeah, firstly, thank you, Sean, for inviting us. It's a privilege to be here today, and we're excited to be here, and hopefully people will learn something. I hope it's an interactive discussion. We don't want to just be talking for 45 minutes. We want people to ask questions. We also have a lot to learn. But, for now, I'll start with a small introduction. There's our agenda. So, my name is Rob Bedford. I am one of the co-founders of Franklin Health. We're a contract research organization.

specializing in medical technology and diagnostics, clinical research. I lead up the clinical operations, department. My expertise is pretty much clinical operations. I started my career as a neuroscientist working on treatments for inherited forms of blindness, and then almost by accident found myself in the medical device industry. I started my career at the very bottom, so the most exciting part, in some respects, is as a study coordinator, I worked with the patients and the doctors to recruit patients into clinical trials. And then since then, I've worked in industry, leading programs of clinical research for very large manufacturers, such as J&J, Stryker, Smith & Nephew, Kaiogen, so my entire career has been, focused on leading clinical research projects for, large manufacturers.

And so my counterpart, Laura, I met when we were on opposite sides of the sponsor CRO table. She brings to Franklin Health the CRO expertise, so I'll just pause there and let Laura introduce herself.

Thank you, Rob. Yeah, so my name is Laura. I kind of started my career in something totally different. I started as a physiotherapist, pediatric physiotherapist. So the first 5 years of my career, I worked as a physiotherapist. gained a lot of experience also, really, on the floor, if I can say it that way, but then also found out quite quickly that the actual practical work of being a physiotherapist wasn't exactly what I was looking for, which I didn't realize during university, because we did have this very scientific approach at that time. So then I kind of found my way into clinical research, and I started off right away

where I am still right now, with medical devices and in vitro diagnostics. So I started my career, really, as a regulatory specialist and also safety specialist. in a very small CRO that was in the end acquired by a bigger fish. So I was acquired with that, and spent some time at a bigger CRO, that was IQVIA at that time, and then I moved to ICOM. I always stayed within Study Startup, so that is really what is my passion. I am fully focused, as I said, on medical devices and IVDs, so this is really, specifically within the EU, a very interesting landscape, so I'm quite happy, actually, Sean, that you invited us, that we have the opportunity to talk specific about study startup.

Because in many ways, it's kind of the important, or one of the most important phases of the study. If things already derail during study startup, that's just not a great start for your study. So yeah, happy, happy to be talking with all of you about this. Again. we have quite some slides, but just feel free to interrupt us at any time. If there's any experience you want to share, any questions that you have, we're so happy to just have a discussion. Yeah, and I hope it will be interesting and helpful for you all. So if you can go to…

rough. Sure.

made proper.

So, yeah, I'll only be brief on this, because really what I want, the purpose of this webinar is for people to learn, and for us to communicate some of our, experience, and also to have the opportunity to learn from others as well, so it's not a sales call or anything. We are a med tech-focused CRO, we don't do pharma or biotech, and we provide end-to-end regulatory and clinical services for both device and diagnostics companies worldwide. We're based in the UK, we have an office in Denmark, and we also have one office in Spain. And one of the unique things about Franklin Health is that we only work with small and mid-sized medtech manufacturers. So there's no, giants that are going to come along, offer a large project, and then we're going to move the team over. We only work with the small to mid-sized manufacturers. And our mission is just to help the innovators generate the clinical evidence they need to launch, grow, and stay ahead.

That's a little bit about us. Okay, so the scope of this webinar is delays during study startup. So we have, a little timeline here that Laura is going to go through with you to think about some of the times when delays can appear during study startup, and then in the following slides, we're going to figure out if we can maybe reduce the scope of those delays, and we have some Solutions and suggestions.

Yeah. In the meantime, Rob, I see a question in the chat. If we work with startup software as medical device… studies as well. Do you want to.

Nope. Of course, yes. To answer your question, yes, we do. We're currently working with a software as a medical device client at the moment to, support their study design. We are in close communication with Scarlett. They're the notified body for Software as a medical device, so, we have an open, communication platform with them, so we can support with study design. clinical trial execution, and then liaising with the notified body. So yes, we, we do have some recent experience with this. Question.

And very relevant, huh?

Yep.

So, what I wanted to talk you guys through with this slide is how important it is to have an efficient study startup phase. Put some numbers in there, not to shock you, but just to make sure that we all know what we're actually talking about. So, study startup phase can take a very, very long time, starting with, of course, the design of the study, which is typically to four months. then it actually can be quite different, for site selection. Obviously, depending on the number of sites. It can take one month, if you only have a few sites, but it can also take 6 months if you have many sites, if it's difficult to actually select, because you have a specific indication, specific requirements, so you can already see that as from the moment of site selection, things can already take quite a long time. And then we have regulatory submissions.

So, ethics submissions, competent authority submissions, IRB submissions in the US, but also contracting, and also these kind of timelines, you will see, oof, it's a wide range, no? It can be 2 months, but it can also be up till 7 months. Contracting can be up till 12 months, and you'll be like, wow. too much, and it definitely is, and that's why we actually have this webinar, because we just want to walk you through the experience that we have in actually being able to reduce those timelines and be able to start up your study efficiently, pull it all a little bit together. I think, Rob, if you click one more.

We also have patient recruitment, of course, which is part of study startup, but of course also, when the study is ongoing. If you can go to the next slide, Rob, I think we will just go ahead with the first one that we want to tackle, which is study design.

Yes, so, when thinking about a study design, so manufacturers of devices and diagnostics, they will have three things in mind. They'll want to design a study that One is, is going to be good for the regulators. So, when you're thinking about a clinical trial design, you have to satisfy the regulatory frameworks and the pathway from which you're getting your device to market. So, you're going to be thinking about your endpoints, your objectives, do they meet the regulatory requirements? Will the study design allow me to perform the analyses? Am I going to have a sufficient patient population? Is it statistically powered? And also, fundamentally, and this is what the notified bodies and FDA look at, does your study demonstrate performance, safety, and clinical benefits, depending on the class, risk profile? So, when you're thinking about your study design, you have to have in mind what the regulators consider as best practice, and one of the ways that you can

give yourself the best chance for success, is looking perhaps at what your competitors do, what's on the literature, how do you demonstrate clinical benefit of device X, and then you can work backwards and design a trial design that allows you to fulfill those objectives. When you're also thinking about study design, you also have to be mindful of the clinical sites, because not only do you have to satisfy the regulators, you have to design a clinical protocol that is going to work in real life. So, you think about the hospitals, the doctors, the surgeons, these are the ones who are going to implement your protocol into practice, and so you have to be mindful of how this is going to work in real life.

So, some important questions, you want to know if the data that you want to capture, is that available during clinical practice? Are the doctors, nurses, surgeons, study coordinators, are they going to have to go out of their way to collect this? How much data do I need to collect to support your endpoint analysis? Is the visit schedule reasonable for both the patient and the site? Is the volume of data to be collected reasonable? Are you asking 10,000 questionnaires, collecting so much data, and in the end, the regulators only care about 10% of it? Are there any red flags for an ethics committee? Are you going to have

15 PET scans in a week. I know that's an exaggeration, but you need to be thinking about possible delays, and so this is the most important one for the purpose of this webinar, is delays from the clinical site perspective. And then also, finally, are there any complex activities? Is there anything that you're wanting to do in your clinical trial which deviates from the norm in such a way that you're going to have issues with the hospital, with ethics committees? And then the final one, this is not necessarily relevant for the, for this webinar, which is delays to Study Startup, but it's something that all manufacturers will be thinking about.

Is my device solving a problem for hospitals, for doctors? Will my device provide clinical benefits? Does it provide economic benefit? Does it bring costs down? And also, when I ultimately bring my device to market, is the cost of it going to be in line with hospital budgets? And is that commensurate with improvements in outcomes? So these are the three, factors that you need to consider when building your study design. So the one I'll focus on briefly today is the clinical sites. So this is how, this is the best way to think about it, if you're thinking about hospitals and where your study's actually going to be run. So, you can have the best protocol on paper, and I've seen this many, many times, you have

1,000-word protocol, written by geniuses, it's fantastic, but in real life, it doesn't work, because this study needs to be delivered by human beings who have schedules, they have patients, and probably 90% of their time is spent not on research. So these are busy doctors, busy nurses, so you need to make sure that your protocol is not only great on paper, but is workable, in real life. I can think of an example for a robotics study that I led a couple of years ago. The sponsor wanted to collect lots and lots of, real-time data about this, robotics, this surgical robot, and that meant the patient was going to have to be,

undergo anaesthesia for a little bit longer. So, they got to the very end of the process, and the clinicians said, well, no, we're not going to do that because the number one factor is patient safety, and then they had to go and revise the protocol. So, how can you fix that? My advice would be to engage clinicians and site staff in the development of the protocol as early as possible. So, when you're drafting the protocol. book a call with someone who's going to actually utilize this protocol in real life, and then also the ECRFs as well. If you have ECRFs that are perhaps not standard questionnaires, they're more bespoke questionnaires, go through these with the site as well. Make sure that your protocol is going to be workable in real life.

The second delay that I often see, is where you have activities that deviate a lot from standard clinical practice. What you really want to do is to try and keep your clinical trial as close to standard practice as possible, so that the data collection becomes an extra piece of work, rather than a huge activity that they need to undertake with lots of training. An example I have is I worked on a dementia study. several years ago. And the sponsor wanted to collect some neurophysiology measurements, which involved lots of weird and wonderful equipment and lots of specialists, and they spent ages and ages and ages on the site setup activities, trying to find neurophysiologists at each hospital to collect this one questionnaire that didn't even end up being submitted to the regulator anyway. So, be pragmatic, be simple.

try and reduce the amount of data that you can collect that satisfies those three, considerations I mentioned on the previous slide. And again, engage clinicians and site staff in the development, to see if there are any of these, potential delays. And then the final one is are you going to cause any safety risks or excessive strain to your patients? Are you asking for 5 lumbar punctures when you can only use two? So think about what an ethics committee will think. Think about the human realities of your study, and because these often can lead to delays and pushback from the ethics committee revisions of the protocol. So, for me, these are top three delays.

Sean, I'll just pause there for a moment in case anyone has any questions.

Yeah, I think it would be a good time to ask the audience if they have any actual experience with any of these, you know, study delays, or engaging with the clinicians, or, you know, where the rubber meets the road, I think is a really good. Framing for this is like, yeah, it looks good on paper, and then, you know, you put it in the hands of human beings, and… And it goes sideways the second you do that. You know, our best thinking only gets us so far, and then… reality strikes. So, anybody had any experiences with this that they wanted… Chime in on? That's online? I don't know.

I'm happy to chime in.

Hi, Arlene.

Hi. So, I run the Society of Physician Entrepreneurs. And these are a bunch of folks that are trying to get ideas to patients and engage pretty much everyone on this audience. And just to lend the experience that it's a two-way street in terms of how clinicians work with non-clinicians that they need to help them get an idea to a patient like you folks, and vice versa. How do you engage clinicians at the early startup stage, and when I say clinicians, I mean Pharmacists, nurses, dentists, health professions, any health profession. Now, I'm based in the United States, and I totally understand there's a different culture in other places, but…

Fundamentally, the problem is the same. Which is, how do we connect the dots And how do we do it in an efficient way that is cost-effective For people that really don't have a fundamental understanding Particularly in medical device, software as a medical device, etc, and all the AI risks that are associated with it, so… So I'm interested in your ideas as to how do we close The data doctor gap So that… because we're always saying you need clinicians early in the product development phase. But when it comes to execution, actually making that happen, there's significant barriers, so I'm interested in… how do we do that? How do we close the gaps?

Yeah, good question, Arlen. And, I acknowledge those challenges. I'm assuming you're meaning financial challenges. If you want to engage a clinician early on, they often will expect payment, and they are quite expensive. And then also the patient side as well, they're perhaps less expensive. And I know you mentioned that you were in the US. We're in the UK. One of the requirements for UK submissions, in, for clinical research is that you need to demonstrate that you have involved patients in the design of the clinical study, so you need patient and end-user, involvement. So… typically, sponsors do have key opinion leaders or experts that they work with, and what I would recommend to our sponsors is that they engage those, as part of the design process, just to make sure that, as we've described here, that a protocol is workable in practice. However, if you're a smaller organization, you may not have

10 different key opinion leaders on your email contact list. So then, perhaps organisations such as yours, Arlen, maybe you could tell us a little bit more about what your organization does, and how you could possibly help?

Sure. We're an international… so the Society of Physician Entrepreneurs is something that's been around for now 14 years. We launched it as a, a non-profit, so we're an international, non-profit, open. biomedical and clinical innovation and entrepreneurship ecosystem. In other words, anybody can join, which is why I'm on this call, because I want you folks to be in the game, and… Not that you're not, but this issue of, well, how do we help people find you? I mean, it seems to me that's a straightforward dating service platform. You know, here's what you do, here's how your expertise, etc, etc. It's like a… and then folks in our network can go to that site.

put in a search term, I need medical device regulatory affairs, or AI, whatever, and then put up a list of folks and how to contact you and your information.

Yeah, I agree with you. However, I have to point out to you that you're talking about a two-sided marketplace, which is there's nothing deadlier in marketing than a two-sided marketplace, and that there have been plenty of people that have tried and failed, much better people than I. And so, what I think the point is, is that It's… you're marketing to two completely separate audiences, and you're trying to build a platform. So, in terms of the technology, yes, the technology is very simple. But the marketing challenge is very complex. I don't want to go down that road too far, but other than to say we are trying to create an ecosystem that supports all players in the field, and then to say, you know, let's engage on this

offline, because I don't want to get off track, too far from, today's call, which is really about Study startup. So, not to cut you off, Arlen, because, I appreciate your. Contribution, but that's moving down a branch that we don't have time to get into today. That's all.

That's fair. I'm happy to talk about this offline. I'll put the link on the thing, and I'm happy.

Yeah.

If they saw online.

Me too.

Great, thank you. But it's a great point, Arlen, and I think patients should be involved in study startups, and I think if they are involved, then that will reduce delays. So, yeah, we're happy to, I'd love to chat to you more, after the call. So thank you for that. Okay, we'll now move on to some of the delays caused by site feasibility and selection.

Yeah. Thank you, Rob. So yeah, for site feasibility and selection, as you know, as you can imagine, there is so much variability in between how sites perform and how responsive they are. So that's something that we are dealing with on a daily basis. Now, when thinking about some ways to overcome that. There are quite some things that we can do, luckily. So, for example, if… And that may be a bit obvious, if there are some existing site relationships that you already have. as a sponsor, or that your CRO has, then that is one of the key factors to leverage. Because if you know that sites have been high-performing before, if they have been activated before, that is already a great indication that that relationship can go well, and people already know exactly how they need to collaborate.

Besides that, because I acknowledge not everyone has a huge site network that they can leverage, there's some other things, of course, that we can do. And one of those is to make sure that from our side, the feasibility process runs as structured as possible. really to slim it down to what are the actual key factors that you want to know, and include only the decision-critical items. Make sure that your questions are also not ambiguous, know that it's quite clear what you… what the answer is that you would like to get out of that feasibility questionnaire. And also, if sites are already unresponsive at an early stage, that is an indication for how it will be going

further down in your study, so take that into account as well. Some very important things to ask early on are. local approval requirements, because, you know, in countries, it could be that you have, on national level, you need to get competent authority approval, you need to get ethics approval, but then you get into the weeds of it, and some sites also need their own local approvals, and those can sometimes even be longer to obtain than the actual competent authority and ethics committee approval. So, it happens often that you get, to a point that a site is already selected and only then you find out that there is an additional approval that derails your home timelines, which is why it's so critical to include that into your whole feasibility process. Same thing with contract negotiation timelines, or if there are any kind of templates that the site needs to stick to. Really make sure that you have that information straight, and that you can make decisions based on that.

Of course, at all sites, and Rob and I were talking about it earlier, all sites will be telling you that they have the greatest recruitment potential, that contract timelines are basically from today till tomorrow, so it's really also important to look a little bit beyond that. And to make sure that, one, you request some objective evidence of that amazing recruitment potential, but also that you actually get to know your site. So if you have the possibility to go to the site, to actually talk through things with them, to make sure that they really understand the study, what is required, what is needed in terms of training and facilities, that is really key to make sure that you actually

can go smoothly and select the right sites. Also, could be kind of an idea to select a whole, or at least to run feasibility on a whole. bunch of sites, which will only increase administrative burden for the sites, and also for yourself. So make sure that you are going to reach out to just the right number of sites. Another thing you can do from your own side is to make sure that you reduce the bureaucratic decision layers. Fancy way of saying, like, make sure that if there are any decisions that your CRO can make for you, for example, a CRA can ad hoc already see, like, this is not going to work. Make sure that they also have that decision power, so that not every decision needs to go up to the sponsor, because all these kind of different layers of communication

Lead to delays as well. And value proposition, of course, and make sure that the site really understands what the relevance is for being in the study. Scientific relevance, for example. Access to novel devices can also be financially, you need to be very transparent on what it actually means for them. So all these kind of things are really important to take into account. So how do you do that practically? On the next slide, we just have a few questions that, that can help you.

Yes, so one of our…

printed?

Sure, sure, Laura. Yeah, one of the things that we have to do, one of our challenges when we're running through site feasibility. Is to cut through the noise. Because when we're, prospecting sites, trying to find out which are the best sites, typically a site will tell you, yes, of course I can deliver this study, I have access to a million patients, we've done many, many studies like this before, we have the best equipment, because they all want to win the project, they all want to be paid the large sums of money that you receive for running, a site, so you have to read between the lines, and you have to be able to ask

the more difficult questions. So these top seven questions are very basic questions, which will perform the part of every feasibility questionnaire. So we want to know, have you delivered a study like this before? Do you have access to the right patients and sufficient numbers of patients? Do you have the right equipment, the right facilities? Do you have the right experience? Do you have dedicated study coordinators? Are you running any competing studies? Because often the very biggest sites have got six orthopaedic studies, and they are then competing for the same group of patients. Do you have time to deliver the study? And also, fundamentally, what are your local approvals timelines? Because if you have lots of weird and wonderful local approvals process, this can really derail your first patient in. So, how do you cut through that noise? Visit the site, you should be

doing this as part of site qualification. Don't just rely on the questionnaires on their own. Ask for specific examples when referring to the questions. Run through the protocol synopsis. This is the most important one for me when I'm doing a site qualification and feasibility. Have a brief run-through of the protocol, talk about the endpoints, the objectives, the patient population, the eligibility criteria. you'll find the very best performing sites will have, that's meant to say, lots of questions. They'll have lots of feedback. They'll say, hmm, not sure about this part of the protocol, what about this part? They're the very best and most engaged and most proactive sites, so, it becomes clear the people that just say yes to everything, and the ones that are actually going to deliver your study on time, and they're going to be your best performers.

So yeah, good, thorough feasibility can save huge delays, in the long run.

This is Dan. Just wanted, along what you're discussing here, I think that those are great questions, but obviously, I think you pinpointed quite correctly that some of these questions, they will definitely say yes, even if they don't have it. But obviously, I think that When it comes to clinical studies, it's all about, also, documentation generation, and that documentation has to be reliable, has to be trustworthy, so… so whatever means of data and documentation generation capabilities they have, whether it's electronic and or… you know, paper. It is, to me, important to sort of keep track of that. The experience with applicable regulations, a lot of these clinical site studies, they may not have really experienced understanding exactly what it means to do the clinical study.

And to me, the third one is, what's the workload they have? Because if they're… if they're a site that are just willing to take studies, the workload may be so overwhelming that they may just, have you know, one clinical study competing against another, and then, in the end, they're gonna give you average work. Just talks for… from my site.

I… my experience, too, is what… depending where it is, the paperwork is overwhelming for a lot of them. When they go in and see the actual… what it takes to run a study, and the… they are overwhelmed with the amount of paperwork.

Hmm.

And they think it's ridiculous. They're like, are you.

as soon as we.

I have to fill out all this paperwork.

So… Hmm.

Having somebody go in there and hold their hands is key.

And to your point, Carrie, data integrity is as vital when you're running a clinical study as it is when you're running a commercial production operation.

Jack, you have to have… They do have to have the clinical trial folders.

Absolutely. And have the D.

Keep. You know. And you have to have the surgeons, you know, make sure they're… filling out the paperwork, because a lot of times you go in there, the doctors don't want to fill that out for you. They think it's ridiculous. And so you have to have somebody holding their hands as well as the assistants and… Informed consents are very important.

Totally right, absolutely right.

It is, yes, and I've worked with many sites who are small, perhaps it's one of their first ever clinical studies, and it can go one of two ways. So, often the sites that have not worked with clinical trials before, they're so engaged, they want to do everything right, they think, oh, I need to get this right. But also, they can be completely overwhelmed and think, oh my goodness, all this paperwork, I'm drowning in paperwork, and it's… it's new to them. The idea of GCP, the idea of an investigator site file, a regulatory binder, is new to them, and they think… and so with newer sites, I would say setting the expectations early is really important, because when you go to Duke University or Stanford, you know they've got thousands of research coordinators who've done this many, many times. You don't need to train them.

But if you go to a small family clinical practice, they may actually deliver the study fantastically, but they'll probably need more of a learning curve. They'll probably need more guidance, as you go along, so… Yeah, exactly, exactly. And I would always recommend… With a smile. Smile, yeah. Exactly, and they can sometimes be fantastic, and I would always recommend to sponsors, having a mix of large sites and small sites. So, if you have old dukes, you'll never get your study started, because the contracting will just take years and years. But if you have really small sites. you know, there's some risk there. So, yeah, fantastic points. Thank you, Daniel and Carrie. Appreciate that.

I can see, Andrea, you have your, hand up.

And, so… With the feasibility question is, so… I can recommend get in contact with the sites. I had A lot of studies. Where we sent out the feasibility questionnaire, and later on, we had difficulties, because they mentioned numbers, they could not even get into the study, they did not really read, they just wanted to participate. So this is something, get in contact, really ask. If they have all this, Patients available if they really think they can get these patients in. And so this is very important, and then also…

Usually, the feasibility, and later on, you send them a synopsis or the protocol after you have a CDA, And, then you need to make sure that they really understand. For example, if there's… For a comparison, so controlled study with standard practice. Usually, standard practice, but to have it comparable to the new or device under investigation, you… they need to… have a different practice, or maybe they are not allowed to use A special disinfectant or something like this.

It needs to be clear, so this is something… sometimes you can get into trouble when they already start. They agreed to everything, and after that, they start complaining that it is not per standard routine. And then they don't want to do it, and you cannot involve these patients anymore, you need to exclude those, because they just do not want to cope with the protocol, right? So this is something, a feasibility… a question is sent quickly.

Yep.

But, and they complete it quickly, but it's really neat, so always a little bit more time, and if… So, if it is a small new CRO like yours. I think what you can always do is, Let the people know, the sponsors know, that you have more time. For smaller projects, that you can also, you know, that you can, work more hand-in-hand. With the side. get direct, so it depends on what you… want to… what studies you want to do, you know? But… so… and if you go to other countries as well, so just collaborate with other small CROs in that country, or overseas, or something. So this is something that's very good, but…

Thank you, Andrea.

Yeah, she brings up an interesting point about working with small CROs, and I've heard this a lot. You know, one point that I would like to drive home is that when, companies go to work with the larger CROs, they're often, deprioritized. So, particularly for small to medium-sized, medical device companies seeking out the smaller CROs is probably a best practice.

Yup.

Laura.

I mean.

Want to continue?

Sure. My favorite topic. So, regulatory and ethics submissions. If you can go to the next slide, Rob, there are a few things that we can do to make sure that we go through this whole regulatory approval process as smoothly as possible, as fast as possible. the first thing I would want to touch base on, and it may sound like Of course, no, but in the real practice, it's not, is that the whole team is actually aligned on the design of the study. on the risk that is involved in the study, on the classification of the device, the marketing status of the device. If you can put that in a memo that can be distributed to everyone, honestly, I recommend it because it happens so often that a wrong submission pathway has been chosen. You can imagine you go into the validation stage, it takes, what, two weeks, a month maybe, and then in the end.

an authority or an AC tells you that you misclassified, and you need to resubmit and do it all over again, because the requirements are also different depending on the regulatory pathway that you're choosing. So you just don't want to end up there, and that is why it's important to just spend a little bit more time in the beginning to make sure that the teams are aligned. And… and make sure that all that understanding is, or that everyone is at the same page. The other thing is related to, validation, so the validation of the package. So, most of the authorities, NECs. usually as well, they first do a validation check, so just to see if all of the documents are there, if it's compliant with the regulation that you're working on, whether that's EUMDR, EUIVDR, or the regulation of any specific country. It's just a quick win, I would say, because there is a lot of guidance available, a lot of competent authorities, like, for example, the MHRA in the UK, they actually have a checklist

That tells you exactly what you need to submit. Of course, in EUMDR and EUIVDR, there is also other NXS that tell you exactly what it is that you need. It has been quite some time, quite some years after MDR and IVDR came out, that it was Unclear. Maybe sometimes it is still unclear what it actually is that you need to submit, but I feel like authorities have been catching up quite a bit, so do the research, make sure that your packages are valid, so you can move through that phase quite quickly. Another item would be related to versioning. So there… you will, of course, or if you have a multi-country study.

you will have different submission processes in the different countries. It could be in some countries that you, in the EU, for example, need to submit to a competent authority and an ethics committee at the same time. and then the ethics committee gives you feedback on the protocol, for example, and that is being upversioned to a new version, then that needs to go into the package of the competent authority at some point as well. So you can already see that these versions, and if that's just one country, that these versions can sometimes lead to quite some mix-up quickly. Could also be that, for example, an update requested by one authority in a country

is actually also quite relevant for the other countries, in which way you will also need to make sure that those versions are aligned. So, it can get complicated quite quickly, so have a good system in place to make sure that the right versions are submitted everywhere, that the same version in the end is approved. In all the countries that it needs to be approved in. So that is, maybe a small tip, but it just avoids a lot of headache in study startup, but you can only imagine also further down the line, of the study that avoids a lot of problems. the biggest, issue, if you can call it that way, is that even though, for example, in the EU, which is my favorite example.

there are regulations on EU level, like the EU MVR, EUIVR, there's still so many differences in between the actual countries. So that's why it's important that you partner maybe with a CRO that has that exact specific knowledge, as we were already talking about. Partnering with small CROs that have the local presence, that know exactly what needs to be done in which country is so important, because even though it's regulated on EU level, which kind of competent authority submissions need to be done. In every country, it looks totally different, because it can be that submissions are parallel tracked, can be that, for example, local approvals are still required, as we already mentioned, but also some countries, for example, want you to first obtain Ethics Committee approval.

10 competent authority approval, can do it in parallel, can do it combined, so you just need to be actually sure about what kind of pathway, you will need to go down to. And also for your sites, it's really important, because the burden on the sites can sometimes be very high. I think, Sean, you were mentioning something in the chat about Germany. Germany is the perfect example, as well, of how complicated it can sometimes get. You need a lot of, for example, certifications that testify that the investigators actually have experience with medical devices, and with the actual regulation, or with IVDs and actual regulation, you can need to obtain, for example, a lot of signature pages, not only from the principal investigator, but also from other investigators, like everyone almost involved in the study. So it can get complicated quite quickly, which, again, why it's important to just make sure that you have that expertise, and if you don't have it as a sponsor, that you partner with someone

That, that has that. I feel like time is going quickly, so I will not be going into too much detail, just A lot of differences in between countries.

In the US, for example.

announcements, if I may. easy and quick way of doing studies. Just want to tell you as well that even in the US, there are also quite some differences in between sites, that, for example, some sites can accept central IRB review, others will need to involve their own local IRB, or need to issue other reliance agreement to go to the central IRB, and then there is a whole bunch of, local approvals that you can also… may need to obtain per site. So, on paper, can… can go fast. Like, a central IRB review could be, like, just one month, even maybe two weeks, but then again, there's still so many other factors to take into account also in the US, so…

Depends, on what you're actually looking for.

Just a quick announcement, next week, on that Thursday, we're doing an MOV webinar. With Agriteam, and with Rich Holboro from BSI, and another speaker, whose name I can't remember at the moment, Clinical Data Transferability Strategies for Leveraging Cross-Regional Evidence. Somewhat related to this. Anyway, that's my announcement. Sorry for the marketing interruption.

Quick commercial.

That's perfectly fine. Thank you. And then the EU? So, most of you are probably familiar with it, if you can, yeah, click through. So, in the EU, we have, of course, I mentioned it several times, EUMDR, EUIVDR, the combatant Authority approvals are regulated, per those regulations, you can find exactly what needs to be submitted. All looks quite easy and straightforward. In practice, a little bit different, because there's still so many country differences, even for competent authorities. again, also for ethics committees, because it's not… the only thing that is described in the UMDR IPDR is that you mostly will need to obtain an ethics committee approval, but how that really looks like is then still quite different. Some countries have central ethics committees, some have locals, so yeah, that is… that is something that you need to take into account.

And then the site-specific approvals, as we already mentioned several times. So that means that, if you can go to the next slide, Rob. that we still see a lot of, oh, it's not on this slide. Can you just go one forward, and I'll just go to that one first, and then back? I mean, two… two slides further, so not this one, but the one after. Yep, thank you. So here, for example, I just, you know, took a sample of a few countries to just let you know what it really looks like, even though the regulation is the same. So, for example, Belgium, if you have a pre-market study, but I'm just focusing on that for the purpose of this presentation, if you have a pre-market study, you can actually just submit to the competent authority, and you will get one nice consolidated opinion from ethics committee and competent authority, which is great. Also, the competent authority is very approachable for questions.

There may be some local approvals that are needed, depending on the site, but in general, in Belgium, it's quite straightforward. In France, for example, it's then different, no? It is a parallel review, so you need to submit a separate package to ethics committee, separate package to Competent Authority. In France, there are also some other bodies that are involved, like, for example, for data protection, you have the KNIL, For contracting, if you're not using the standard contract, on national level, the Contraunique, you have Knom, which is another body that is involved and needs to provide an approval.

Germany, then, again, favorite country, you need to do a sequential submission. So first, ethics committee, then competent authority. Also, local ECs are involved there. As I already mentioned briefly, extensive requirements for the investigators. You need a national coordinating investigator, so… This whole purpose is not to tell you, all the specific… all the specific countries, but my bottom line is just… make sure that you… that you know the specifics of the specific countries, because there is quite some difference. In the Netherlands, for example, they only have a validation, so only the… of the competent authorities, so the CCMO will only look at whether all the documents are actually there, but then the actual review is being done by an ethics committee, and per site, you have a very specific suitability process, and you need to obtain Board of Directors approval.

sometimes also technical device review. Yeah, again, quite, quite some differences in between the different countries. If you can go back one slide, Hope. Yeah, luckily, there is some alignment, ongoing in the EU, from the European Commission, so I have seen some initiatives, for example, this pilot coordinated Competent Authority Assessment for Clinical Investigations and performance studies. I recently noticed that the deadline to be entering into this project has been extended, so it's now until the 30th of April, and it's really meant to, as it says no, to coordinate the competent authority approval process. So it could be both for medical device studies, as for in vitro diagnostic studies. It's a pilot project, so it doesn't mean that you do not still need to get an approval of each country, but I'm happy to see that there are steps into

the right direction, I would say, to actually get to some more alignment. Another example is a combined project, which also has… it's specifically, for combined studies, but they also have this kind of all-in-one procedure pilot project, which is specifically for studies, both with the EU CTR involved and the EU IVDR, or MDR. So that call is currently closed at this point, so you can no longer participate in the pilot, but also a very exciting project, and I'm happy to see that at least there is some Or some initiatives, for alignment in the EU. That was all on regulatory and ethics committees. I don't know if anyone has any question there.

show the, coordinated assessment program. Again, you know, I've heard talk about this thing. Happening, but some countries won't lead, they'll only follow, and it is…

Yep.

Is it an added layer, or is it helpful? And when is it going to be real?

very valid questions and things that we obviously are all asking ourselves and don't know at this point. I've been on a webinar, actually, someone was asking, with the European Commission, someone was asking the exact same question. they're very political, no, so it is a pilot. There is no, actually, information about how this will actually be rolled out, and when this will be rolled out. Of course, we need to give them some grace, this is not an easy exercise, but yes, at this point, it's something that Remains to be seen if it actually, within the pilot project, helps, to reduce your timelines, because as you can see, it would be…

one, it's for multinational studies, but as you say, Sean, not all countries are participating, or at least not as a reviewing member state. So it could be that you then are going to participate into this project. It takes two… up to maybe five months to actually get that approval. But you still need to submit on a national level as well. Of course, it will be accelerated, because you will already have an approval from the coordinated assessment, but that step, you still need to do that. You still also need to obtain ethics committee approval. So we'll see how it goes. I guess it's a step in a good direction, and we'll see what the actual outcome will be.

Daniel brings up one of my favorite questions, which is, where does human factors fit into all this?

Human factors is something that all manufacturers should be considering, both when they're designing their clinical trial, and also when they're doing all of their clinical evaluation plan. authoring and preparations. So, whilst not all clinical trials involve some kind of human factors, it is something that manufacturers should be thinking about. My expertise would be to, get some consultation on this, so speak to some experts who have expertise in human factors, because human factors is only becoming a bigger and bigger part of the evidence package required for both submissions to FDA and submissions to notified bodies. So, while not always necessary part of the clinical evidence, human factors is now frequently being required in clinical trial design as well.

to make sure that your device is usable, is it intuitive? Is it simple to use involving the end user and also families of the user, etc. So, yeah, my advice would be to, to work with a consultancy who have expertise in human factors, and perhaps can help you with some volunteer studies, and so you can generate the early clinical, sorry, the early human factor evidence. That can go alongside your clinical evidence.

Beautiful, thank you.

The reason why I asked the question is because If you have a medical device where the patient interaction with it is going to be higher than what the doctor interaction is going to be the clinician. There are different aspects of human factors involved, so you have… you have to keep that in mind. And that's why I was just thinking, but obviously, because human factors do have an impact on the outcome of that clinical study.

Exactly, and if… if you can collect data which demonstrate that human factors has been taken into consideration as part of your clinical study, then that's fantastic. That's more bang for your buck. I'm thinking particularly about wearables, products, where you may have an app. you may have a device, and you can have a perfectly run clinical trial where you generate the outcomes that you need to satisfy the regulators, but patients find the device really hard to use, and it's clunky, and it's not intuitive. If you can capture that data within the confines of your clinical investigation, then brilliant. That's something that you should do, and we're seeing human factors as a bigger and bigger part of the

The never-ending list of problems device manufacturers have. So, yeah, manufacturers should be thinking about human factors from day one.

Perhaps we should do a session soon on human factors. Okay, the.

Nikhil, you have a question. Comment.

Yeah, hi. So, this is Nikhil. Nice to see you, Rob, again. So this is largely around the ethics, you know, so there is a large shift towards a move for real-world evidence data collection in EU and in the UK. What do ethics and authorities think about this? Do the studies need to be designed as robustly as other clinical trials? Are the processes more simpler? What's your take or experience designing these surveys?

Yeah, I mean, I wouldn't rely on a regulator or a notified body, accepting a lower level of clinical investigation with the promise to do real-world evidence, unless you had that pre-agreed already. So, sometimes you can have an interaction with a notified body, or indeed FDA, and you can agree to these real-world evidence, post-market follow-up. But I would make sure that your clinical trial design is well-structured and meets all of the requirements, regardless of your real-world evidence. However, to your point, Nikhil, I think the regulators are becoming more acceptive of real-world evidence studies, and it's more intuitive. A clinical trial is a very prescriptive experiment with clearly defined boundaries and

parameters, and it's kind of artificial. It's not how a device is going to be used in the real world. So I think the regulators and the ethics committees are, becoming more supportive of showing the benefit and safety and performance of your device with, real-world evidence, studies, because that's actually how it's been used in real life. So I think we're moving towards a real-world evidence post-market, demonstration of how, effective, safe, and performance of your device, but I think it's a shift rather than You know, thinking that, oh, I'll just do real-world evidence, I'll have a much smaller scale clinical trial, fewer patients. So yeah, great question.

Sean, we can maybe do a session on real-world evidence as well. Real-world evidence in silico testing, human factors, there are a lot of components that go into this, but what I would like to ask is, where does AI fit into all this, and how can AI, facilitate study design protocols, what… What does the CRO of 2028 look like?

Gosh, we have 3 minutes, Sean. How do I answer that in 3 minutes? Because we do have other points that I think we're perhaps not going to get to now. So…

We'll put that on hold.

Okay, okay, because I could speak for a really long time about AI, and there's lots of very good use cases of AI, there's also examples of not-so-good use cases of AI, so, yeah, maybe we could do a session on AI, but… I'm somewhere in the middle, I think. I'm somewhere in the middle. I think it can help, and it can support, but so long as it's a human being who's making a decision at the end of the day, then that's the most important thing. I'm not talking about software as a medical device, I'm talking about the use of AI.

kind of.

trial design, writing protocols, etc. It can be a useful tool, but I've seen… we would never do this at Franklin Health, but I've seen examples of other CROs who've run protocols through ChatGPT and asked for suggested edits to endpoints and objectives and stuff, and so I think one of the biggest considerations is intellectual property, because once you put something through a large language model, it's essentially into the public domain, and that's one of the biggest problems is where you're giving away companies' intellectual property and confidentiality. So yeah, Sean, you've got me started now. I could go on for hours and hours and hours.

Okay, well, I'm gonna, I'm gonna stop you, and I'm gonna say, let's have an interview about that separately, and I will be more than happy to interview you on that subject. In the last two minutes, we had a question from Luke, and the question was, how do we go about assessing a small CRO, and whether or not The… how do you… how do you pick… You know? Obviously, it's very easy to go to one of the top 3.

Right.

So, how do you assess a small CRO? What questions should we be asking you?

Great question. So I would ask for your recent therapeutic area of expertise. Have you delivered studies like this? I would ask for the geographies in which you work. Are you experts in EU? Do you have experts in, US FDA as well? I would want to know what team are going to be working on the project, how many studies that you have, because with the larger CROs, they're able to operate at scale, and they're able to bring in teams very, very quickly, so capacity might not be as important. I find that smaller companies have better experiences with smaller CROs, because there's that flexibility there, the accountability.

And you can often ensure that the project team that are on the bid defense call are going to be the project team that actually deliver the study, and that is certainly not going to be the case for larger CROs. So… essentially, all the very basic questions, such as, have you done these studies before? Do you have expertise? I would ask them if they utilize any technology, essentially, pretty much the simplest questions. You can tell once you…

May I interfere? It was my question.

Okay.

If you're a startup, you don't do know nothing about contact research, so…

Hmm?

If I ask you a question, have you done this before, you say yes. How am I ever to evaluate that answer? You have to show… you have to show some evidence. You show them, this is a company like yours, and we did the research this way.

Exactly, yeah, so we would… we would be able to show you case studies of similar projects that we'd led, what was… what was the problem, what was the sponsor that we worked with, what did we do, and then what was the outcome. So we can show you examples of devices that we've brought to market, protocols that we've written, and examples of case studies as well. So, yeah, you should always ask a CRO to demonstrate their expertise and That would be part of the bid defense process. So… And the small CRO, small manufacturer relationship is very different, because often as a small manufacturer, you don't really know anything about clinical research, you don't know about all of the things that we've talked through today, so you really need someone who can lead you through the whole process. So you do have to have a

possibly a larger element of trust there. With larger CROs, they have entire departments, dedicated to study startup, regulatory, so, you do need the more, kind of hand-holding, really, and that's the part that excites me the most, is getting to work with the most innovative segment of the market, the people that are new, they may be engineers, scientists, they're looking for guidance to how to bring their device to market, and that's what I really love, so… Yeah, good question. Put me on the spot. Thank you.

On that note, we have to wrap up, but what I would like to say is, reach out to. Laura and Rob, connect with them on LinkedIn, and Luke, to your question, I would say it's like selecting an engineer, it's like selecting a manufacturer, it's like selecting a marketing agency. And really, you have to trust your instincts, and you have to form a connection with them, and you have to understand if you're just being handed You know, a template for an answer, or you're being given advice that's individualized to you, and I think that, you, you can… you can smell the difference. And

That… that would be my advice on working… working with any expert, in our… in our field. Do we have any final questions, before we sign off? And so, you know. I assume you're open to partnerships. We're looking to expand our partnership platform in 2026, and to create opportunities for people looking for CROs, people looking for human factors, people looking for engineers, people looking for regulatory consultants, and try to find a way that every single company doesn't have to create a partnership program, but can participate in the MLVX partnership program, and automatically be connected with, you know, 50 or 100 Different, you know.

potential or more, you know? So, yeah, anyway, that's it from me. For this week. And, well…

then I would just like to thank you all very much. Most of all, you, Sean, for giving us this opportunity to speak with you all, to meet you all. It would be great to connect via LinkedIn. We have some more stumbling blocks that we would love to talk to you about if you're interested. And, yeah, thank you so much for being here.

grade. Yeah, thank you.

Thank you.

Thank you, Sean. Thank you, everyone, for your time. I'll see you next week. Thank you.

Cheerio.