Who Owns Patient Data Security in Trials with Rob Bedford, CEO of Franklyn Health | Ep.65

This episode of the MedDevice Cyber podcast, hosted by Christian Espinosa and Trevor Slattery of Blue Goat Cyber, features a detailed discussion with Rob Bedford, the co-founder and CEO of Franklyn Health, a Contract Research Organization (CRO) specializing in serving the medical technology (MedTech) sector. Rob Bedford shares his journey from being a neuroscientist and working within the NHS to identifying a critical gap in the clinical research market. He explains that his company was founded to address the specific needs of small and medium-sized MedTech companies, which he observed were often deprioritized by larger CROs in favor of more lucrative pharmaceutical clients. This lack of focus often left MedTech innovators feeling unheard and struggling with limited budgets and tight timelines. The core of the conversation revolves around the numerous challenges MedTech startups face on their path to commercialization and how a specialized CRO can assist. Rob highlights that for these smaller companies, efficiency in both cost and speed is paramount due to pressures from investors and limited financial runways. The podcast delves into the complexities of the clinical trial process, clarifying the distinction between pre-clinical (animal) studies and the different phases of clinical (human) studies, such as first-in-human feasibility trials and larger pivotal studies. A significant challenge discussed is patient enrollment, which is often the biggest hurdle in clinical research, requiring a delicate balance of finding patients who are both eligible based on strict criteria and willing to participate in trials for often untested technologies. The discussion also touches on the global nature of regulatory approvals, emphasizing that agencies like the FDA often require clinical data from a representative US patient population, meaning studies conducted solely in other regions may need to be supplemented or repeated. A recurring theme throughout the episode is the critical importance of early and holistic planning. The hosts and guest stress that key aspects like regulatory strategy, clinical trial design, and especially cybersecurity, cannot be afterthoughts. They advocate for a "security by design" approach, where cybersecurity is integrated from the very beginning of the product development lifecycle. The speakers warn that retrofitting security measures late in the process is not only more expensive and time-consuming but can also risk invalidating previous software validation and clinical data, potentially derailing the entire regulatory submission. The conversation also clarifies the distinction between responsibility and accountability, noting that while a manufacturer can delegate the responsibility for tasks like software development or clinical trials to a CRO, the ultimate accountability for the product's safety, efficacy, and security remains with the manufacturer.

CROs will do your Medtech study, but it's not their priority. What must it be like for the small Medtech companies? You know, you've got a very limited budget. Responsible is who's doing it, and accountable is essentially who takes the fall if something goes wrong. I did a bit of market research, and together with a few, a few co-founders, we spoke to CEOs of Medtech companies and they all said the same thing. We are just completely unheard. CROs don't care about us. Accountable if things go well, you're accountable if things go wrong. From a cybersecurity perspective, if a manufacturer delegates somebody else to create their software, and there's a problem with the software, the manufacturer is the one accountable as well. Hi, welcome back to the Med Device Cyber podcast. Today we're going to talk about CROs which are a very important part of the ecosystem for medical device manufacturers and an often misunderstood part of the ecosystem. There's a little bit of confusion if it's a contract research organization or a clinical research organization. So we're going to get to the clarity on that. We'll get to the point on that. Uh, we have a guest here Rob. He is with a CRO, um, relatively new CRO he started. London, or else, I guess Brighton, a little bit south of London. And we have Trevor, our co-host here. He's coming from San Francisco, as usual. You can tell by his background. I'm coming from Tempe, Arizona. I just got back from Korea. Traveled for I don't know how many hours yesterday. Got up at three this morning, so a little bit jet-lagged. So welcome to the show, Rob. Maybe you can introduce yourself and tell us a little about what you do and what's your motivation was for starting your organization. Rob: Yeah, thank you, Christian. It's a pleasure to be here. So for those listening, Christian and I have met a couple of times. Uh, most recently, we, uh, met in Dubai, um, at WHX Dubai. And, um, yeah, he invited me to be a guest of this podcast. So thrilled to be here. I'm the chief executive of Franklyn Health. We are a contract research organization. Um, sometimes called clinical research organization, though I think it's, uh, contract research organization. Christian: Is that, is that the more common term? Because I've heard people use it both ways. Rob: Yeah, I mean it's an all-encompassing term because when you think about a CRO, I always think about organizations that do clinical trials, uh, perhaps regulatory affairs, but it also encompasses other specialist organizations that maybe do testing or manufacturing support. So CRO is kind of a broad term. Um, in the space that we're in, uh, so you're in cybersecurity, I'm in clinical research, uh, contract research organization, CRO typically means supporting the clinical regulatory, um, part of a medical device manufacturer's journey. Christian: Awesome. And I know you, uh, specialize in, like, smaller startups. Is that right? Rob: Yep, that's right. Christian: And what, from a CRO perspective, I mean I could, I could speculate, but I'd like to hear you say, like, what are the differences, like a, a small startup, like what would they need versus a large startup, and why are you specializing in the small ones? Rob: Yeah, it's a great question, and it gets to the heart of our mission and the, the foundations of our company. So, I started my career in academia. Um, I was a, a neuroscientist, um, I was working on treatments for inherited forms of blindness. Um, and that was kind of my first journey into translational research and I loved it. The idea of helping patients, um, helping, uh, fellow man. And I then took a job in the NHS as a clinical trials coordinator. So, I was working with patients to explain what phase three trials were, what a placebo was, a randomized control trial. And it was probably the best job I ever had. And, um, you could see the hope in patients' eyes, and what it really meant to be in a clinical trial because often if you're in a clinical trial you've not got many options available to you. And that's where I've dedicated my career to ever since. So, um, I've always, to answer your question, I'm gonna, I'm taking a long way to answer your question. Um, I've always worked for large manufacturers, so I've worked for large Fortune 500 medical device manufacturers and diagnostics manufacturers. And I've outsourced lots of clinical studies to big CROs, to medium-sized CROs and it's clear, and everyone will agree in the medtech industry, that the focus is on pharma because the budgets are much higher. A phase three oncology trial is orders of magnitude more expensive than medical device trials. And the experience I had was okay. Um, you know, the, the CROs will do your medtech study, but it's not their priority. And I just always had this wonder, this in my mind, what must it be like for the small medtech companies? You know, you've got a very limited budget, you've got investors breathing down your neck, you've got limited runway. And so, I did a bit of market research, um, together with a few co-founders. We spoke to CEOs of medtech companies and they all said the same thing. We are just completely unheard. We are, the CROs don't care about us. And when we do work with the CROs, we're just not a priority because the priority is Medtronic, Boston Scientific. And so we started our organization to only work with this segment of the market. Um, and now I'm going to finally answer your question, Christian. What is the difference? So first is budget. Typically, the small, um, medtech companies, they don't have the budget of the Boston Scientifics of the world. So you need to be very flexible and careful with your regulatory strategy or your clinical strategy because if you're a huge medtech company, you can target ten regions at once and you can have commercial success globally. If you're a small medtech company, you may be thinking, oh, we'll go, we'll go to the US first, we'll get our 510K or PMA done first, get a bit of commercial traction, and then we'll go to EU. So, budget is one, and clinical trials are probably going to be the most expensive capital outlay that you're going to make as a startup company. So, we built our CRO around this, the cost-effective considerations that we have to make. And so we have partners with vendors and and other contributors to the clinical trial process that are more cost-effective. Another thing is speed. So, I mentioned runway. If you're a small medtech company, you've perhaps got three years of runway. And so, every month, you've got a burn rate. You're burning through cash. So, you need to be quick. So, we built our company to be lean. We have a small team. We have lots of consultants we work with. We have a core group of permanent employees, so we can get going very quickly because every month it matters to a small medtech company. Um, and then finally, I would say trust and experience. Everyone in our team has spent their entire careers in medical devices and diagnostics. Um, so you're not going to get someone from a CRO who's done a bit of medtech in the past, but really pharma's their, uh, focus. Everyone, we only work with people who have dedicated their careers to either diagnostics or medical devices. Um, so you get those cost-effective speed, um, and the experience. Christian: And clinical research, is that only on humans, I'm assuming? Rob: Yes, so the word "clinical" in this context refers to human beings. So, um, if you're a medical device manufacturer and you're developing a high-risk device, um, say an endovascular treatment for aortic dissection or something, you're perhaps going to have to do some preclinical work, which would potentially involve animals. So, we don't do that. That's not something that we specialize in. We specialize in the human being. So a clinical study... Christian: That's preclinical, is the animals. Rob: That's preclinical, yeah. Yeah, that's preclinical. Christian: Yeah, I thought it was interesting. I was at MedTech Innovator in Korea and I was listening to pitches and somebody was saying they have this product that helps with type 2 diabetes and they couldn't go to clinical trials until they had animal studies. And they're like, you can't make a pig have type 2 diabetes. So we have to skip that. And they had this whole weird thing where people wanted them to do animal studies but like, they were saying it's super hard to have, make an animal have type 2 diabetes. And they were trying to skip that and go straight to clinical trials. Is that a, like a challenge you would help somebody with? Rob: No, I think that would be for the manufacturer to solve that problem. So, in, in this case, for an animal study, um, you would want to do it on a species that is as close to humans as possible. So that would be pigs, cows, maybe. And you're right, you can't make pigs have diabetes. Christian: I didn't know you couldn't make a pig have diabetes, but apparently it's like damn near impossible, is what I heard. Rob: Yeah. I mean, you can get as close to diabetes as possible. You can replicate some of the pathology, some of the, um, changes in, uh, blood glucose in the, in the blood and stuff. But with mice it's easier, so you can make genetic changes to mice and, um, create a model of diabetes. But you need to test your device in a species that's closer to human beings. So they would typically want to see, uh, yeah, a pig or something. But, but this is not my area of expertise. Christian: I, I just, I'm just thinking about it because I, I just got back from Korea and it kind of changed my perspective on eating pork. Uh, I went to this old, like how they used to live in Korea and they would show like someone going to the bathroom like outdoors and the pigs like they're elevated, the pigs below them like eating, you know, what came out of, out of them from going to the bathroom. And I'm like, I'm not sure I'm ever gonna eat a pig again after watching this, because apparently pigs will eat anything, but they still can't get type 2 diabetes, which I was just thinking about that when I was looking at that, uh, that display. I was like, oh my goodness, this is, this is not good. No more bacon. Trevor: Reminds me of that scene from Snatch. Never trust a man who owns a pig farm. They'll eat anything. Rob: Um... so animal studies are just one of the first steps to be able to do a clinical study. You of course need lots of other evidence to power your study. You need to do biocompatibility testing. You need to do sterilization. You need to do bench top testing. So, there's a whole host of preclinical work you need to do to be able to get approval for a clinical study. And even then a clinical study, you can't just jump straight into 200 patients. Um, "let's test our new device." You have this phased approach. So in pharma, they have phase one, first-in-human, phase two, phase three. In medical devices, it's slightly different. So, you would initially test out your product in a small number of human beings. And the outcomes that you'd be looking for would tend to be safety, um, is it usable? And this is known as a first-in-human or feasibility study. And so, for the first-in-human feasibility studies, often one of the requisites is animal studies, um, to be able to go into a first-in-human study. And then once the safety signals are good, um, and you've not got lots of adverse events or, God forbid, deaths, um, you would then get the go-ahead to do a pivotal study. And this is the, um, evidence you would generate that would then power your regulatory submissions. So, this would typically be a multi-center, multi-site, because you need to demonstrate the reproducibility of your device. And also depending on where you're wanting to launch your product, you would need data from that patient group. So if you wanted to launch your product in the US, you need to demonstrate your device works with US patients. Um, and that would be much bigger numbers because the outcomes you'd be looking at would be efficacy. So does your technology actually improve the condition for which you're trying to treat or diagnose or manage or maintain? So yeah, animal studies, first-in-human, pivotal study, and then you get regulatory approval. And that's the way it goes. Trevor: I think you brought up something there where you're talking about the different types of studies that, uh, that we need to go through as part of a medical device submission process. And I think coming into any one of these studies, looking at it through a single lens, you can get a little bit lost within your own area of expertise. And so, especially with us, I feel like this happens within cyber security since it's the only thing that we focus on, it's the only area of concern for us. But these medtech innovators and these early-stage companies have so many different things to manage. And so trying to time all of this can be really difficult. And I think one thing that does come up a lot during cyber security that makes it difficult is when we're getting ready for any cyber security testing, any documentation changes, any process changes or to the device that we need to make. There is always this constraint, "Well, we can't make too many changes because this is going to invalidate our clinical data." "We can't make too many changes to the software since we've already gone through our full V&V testing against it and we know that this is a safely validated product at this point." And so, it's a really hard problem. I don't know if this is something that you see a lot where manufacturers need to make some changes, but they're, they're kind of in these handcuffs in a certain way where they can't once they have that data. Rob: Yeah, exactly. And we do see this, particularly with medical devices that have both hardware and software components. Um, so for example, say you've got a continuous monitoring patch that monitors some kind of biomarker in the blood, it's linked to a piece of software. You need to be able to evaluate whether this works, whether it's detecting the biomarker with any degree of efficiency. You need to test that out. And there's maybe an algorithm also associated with the software as well and you need to tweak the algorithm. And so, companies who are developing these products are really hesitant to go forward with their clinical study because exactly as you say, Trevor, once you start that study, you can't then go back and make changes. And so, they can often spend many, many months and too many months and years refining the algorithm and making sure it works. And, and it's difficult because I mentioned the burn rate of these companies in, um, every month they're spending cash on salaries. And so, it's very difficult. They have to be very quick in the beginning. And unfortunately, cybersecurity, we have conversations about cybersecurity with our clients, it's not their, you know, they're top of their priority list. They're thinking, you know, animal studies, clinical studies, biocompatibility, and then maybe they think about cybersecurity when actually we try and encourage them to think about this at the very beginning because, um, it's much... I guess you can tell me, but I imagine it's much easier to bake in good cybersecurity from the beginning rather than at the end, retroactively tweak, um, a device or hardware or software, um, to be secure. Is that the message that you tell your clients? Trevor: I saw Christian and I both giggle a little bit when you said that. 100% yes. And I think this is a big thing that we've been trying to spread some awareness around is designing these products with security in mind is really going to remove 95% of the problems that you would face later. When we're getting to this point, and it happens all too commonly, and it's a really difficult situation where we find vulnerabilities, which I can maybe count on one hand the amount of times we haven't found anything. We always are going to find something. Perfect security is nearly impossible. And so when we find vulnerabilities that are going to require changes to the product, these changes, it can be really difficult to do that if you can't make any significant changes to the hardware or the software. I can give one example that came up recently, which was a really creative solution that I've seen. We go through this test, we identify uncontrolled risk in the system, and this has to be remediated before, in our opinion, the FDA would be accepting of it. We meet with the client and we're saying, "Hey, what can we do about this?" You know, "These are the different software changes, we can change the hardware." And they go, "It's too late, we've already validated all of this, we can't make any changes to this." I go, "Okay, well we'll figure this out, I'll be back in the morning." I come back and they filled the, it was a unsealed access port, they filled it with epoxy and they said, "Can you get in now?" And I went, "You know, I can't. Good job. You did a good one there." But there are times where we have fundamental design flaws in the product, where we can't just epoxy bad encryption shut. We have to make significant overhauls to the product that are going to require new software validation, could lead to new clinical results if we're making significant changes to the way the product is operating. It can cause this situation where it feels like you're falling into quicksand. It just, you won't be able to get out of it, no matter how much you're trying to pull out, without needing to start all the way over. And so what we recommend is just starting early, really understanding what are the risks that could happen. The second you have the idea for the product, before you start designing any hardware, before you ever touch any code, what are the things that could go wrong and how can we mitigate it by design as opposed to the bolt-on approach where we try to retrofit security into an already existing device that is generally going to require some pretty significant overhauls. This is especially prevalent when you're getting ready for your submission in two or three months and this is when you decide to cover your cybersecurity as opposed to pushing it out to the early stages of the product. Christian: Why is there such a a challenge with this? I, I, I'm hoping that we're raising that awareness, actionable awareness. I mean you can know something but not take action on it. I guess from an innovator perspective, you got stability, biocombatibility, clinical research, preclinical, you got all these things to consider, and it's like cybersecurity is not on that list. And hopefully it's getting on that list today, but I feel like in 80% of the cases it's still not on that list until the regulatory affairs person says, right before the submission, what did you do about cybersecurity? They're like, "oh, we didn't know we had to do anything about cybersecurity." But they knew they had to do something about bio compatibility. So how do we close that gap? I feel like that gap is still there for the majority of innovators. Trevor: Cybersecurity's kind of the new kid on the block. It used to be biocompatibility that was the problem. Everyone got stuck on, and now I think cybersecurity is just, it's the newest problem, it's something that we're still getting used to. But yeah, Rob, I'd be curious to hear kind of your view on this since you get a little bit more of a holistic view of the end-to-end process. Rob: Yeah, I'm going to be a bit doom and gloom here. So, I work in the world of clinical research and we are governed by this harmonized set of guidelines called Good Clinical Practice. Um, GCP, and this is essentially do no harm and respect the patient, respect their data, and respect their their ethics. And unfortunately, this is built on lots of terrible things that have been done in the past with experimentation on human beings. Started with World War II, other terrible things. And then because of these horrible things that have happened, frameworks have been put in place, the Declaration of Helsinki, to protect the well-being and safety of patients. But unfortunately, these things have to happen first for some groups to say, okay, we need to make sure that this doesn't happen again. And so, as you were speaking there, I was thinking about cybersecurity and it's, you know, not a new field, but, um, it's newer than, for example, biocompatibility. You said the new kid on the block. And I'm just wondering if lots of terrible cybersecurity things have to go wrong before people start really paying attention. Because when things do go wrong, that is when people start paying attention. I'm sure you're both aware of, uh, Stryker and they had an incident recently. I bet cybersecurity is going to notch its way up people's priority list. And so, there are, in cases where things have happened and there have been cybersecurity, uh, failures. But I think for the most part, devices are safe and they are protected. But I wonder if the more things that happen, the more cybersecurity incidents that happen, it will come up the priority list a little bit. Christian: It sounds like you're saying we haven't met the threshold of things going bad enough for people to care about cybersecurity. And we we being cyber security people know that there are lots of vulnerable devices and it's just a matter of time. But I guess from an evidence perspective, people need to see a lot more bad things happen effectively. Trevor: I think it's kind of funny. So right now, the RSA conference is happening in San Francisco, as one of the biggest cybersecurity conferences in the world. I've gone to some of these events and some of the after parties and hearing what people are saying, people on the forefront of different parts of cybersecurity outside of the medical space. And it really does seem like the cybersecurity industry is trying to ring the alarm bells in every capacity. Hey, we're, the train's going off the cliff right now. You know, the AI controls are getting out of completely out of hand. There's nothing we can do about that unless we really start clamping this down. The application of how we're using all of these new technologies, in healthcare, finance, legal data, is really, really going out of control. And so I think the cybersecurity community is really seeing this as an immediate crisis and something where we are going to start seeing these problems come up. I know they've been happening more and more recently. You brought up the recent breach against Stryker, which is another huge attack. Obviously, you know, a casino compared to the health care environment, a little bit of a different scope and a little bit of a different shock factor there. But even recently within the UK, there was an attack against blood centers where there was complete denial of availability for any treatment to patients due to these blood centers getting ransomwared. And they were able to associate deaths due to patients not being able to receive treatment due to the lack of resources within their IT environment. So I think we're seeing more and more of these coming up, but it's not to the scale or to the magnitude that maybe the industry is expecting it to be, and so they're still not treating it as critical enough of a problem. Although, we are seeing this evidence stack up that this is something really real and something that we really need to put on the front of everyone's mind. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you're, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically the expenses you would see would be travel costs, maybe a meal, out-of-pocket costs. The exception is in pharmaceutical industry Phase 1 clinical trials where, you know, you have these Phase 1 units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically, they recruit healthy volunteers to find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta, and it's a very rare event. And so the FDA... ...make exceptions for this. They know that these events are rare, enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you, um, were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But, yeah, frequently studies fail, manufacturers fail because enrollment fails, and enrollment does not get hit on time, the study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q-sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cybersecurity. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q-sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: It's probably so. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to MedTech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you wanted to expand your indication for use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Uh, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical trials because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail. Manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you've mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cyber security. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: That's probably true. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to Medtech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you want to expand your indication of use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks of associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail, manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you've mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cyber security. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: It's probably true. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to Medtech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you want to expand your indication of use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks of associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail, manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you've mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cyber security. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: It's probably true. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to Medtech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you want to expand your indication of use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks of associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail, manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you've mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cyber security. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: It's probably true. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to Medtech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you want to expand your indication of use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks of associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail, manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you've mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cyber security. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: It's probably true. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to Medtech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you want to expand your indication of use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks of associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail, manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you've mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cyber security. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: It's probably true. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to Medtech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you want to expand your indication of use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks of associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail, manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you've mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cyber security. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: It's probably true. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to Medtech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you want to expand your indication of use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks of associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail, manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Trevor: Will some of the regulatory authorities give you some leeway? I know you've mentioned like the FDA would require 50% of participants to be from a US patient sample size. If we have a really rare condition like this but maybe we're able to collect more data from I don't know, Indonesia. Would they adjust that ratio so that you can at least have a broader sample set without necessarily hitting that exact patient population? Rob: Possibly. The FDA have this wonderful communication structure called the Q-submission process, the pre-sub. And it's just, it's brilliant. I wish we had this here in Europe. We have something similar, but it's not quite the same. So, if you had a concern about enrollment and sample size and you thought that you were not going to be able to have sufficient data to support your regulatory claim, you could ask for feedback from the FDA. And you could say, "hey, we, you know, we've got some patients in Indonesia that we can potentially recruit from". And I would get their feedback in advance. And I find the FDA extremely reasonable, extremely reasonable. And so I would get this information upfront. And also, if you can make a good justification why patients from Indonesia are representative of the patient population that you want to treat, then they would understand and they would, they would say yes. It's whether you can legitimately make that justification, physiology and the pathology and the, the makeup of the patient is the same in the Indonesian part of the world. If you can make that justification, then, then you'll be fine. I suspect you probably wouldn't be able to do that. Um, but it's, uh, it'd be an option. Trevor: Yeah, I think we've seen, we've seen similar back and forth with the FDA, um, even within cyber security for using the Q sub process. And so when you mentioned that, I went yeah, we've, we've seen that a time or two. A little bit of a different approach for sure within cyber security. Often times what we see is when we're helping our clients with that, they want to prepare this in the Q sub, they ask, you know, "hey can you prepare the plan?" And so we present the strategy to the FDA and they say, "yep, looks good. Make sure you're covering these points." But, it's a fantastic opportunity to collect early feedback. And we encourage all of our clients to go through it wherever possible with any questions they have, even outside of our specific wheelhouse. Christian: It's probably true. It is a benefit though, because if you do cyber security, just like if you approach the CRO sooner than later, you can get your product to market faster and more cost-effective than trying to change things at the very end as we've discussed. I am curious because when I was in Korea listening to Medtech innovators, there was all Korean companies and they were talking about moving their products to the United States at some point. So what you're saying, Rob, I think I heard you say this. I guess it's dependent on the product and the type of treatment, but the clinical trials would need to be redone based on a different demographic in the United States versus the demographic in Korea. Is that more common than not? Rob: The FDA would typically expect to see at least 50% of a dataset to be from US patients. So, you can have a global clinical study, and this is what we advise our clients to do. If you have the budget, is get all the data in one go. Have a multi-center study that has sites in the Netherlands, in Belgium, in the UK, but also has five sites in the US. So your dataset is then comprised of 50% enrollment from US patients, 50% enrollment from EU patients. You've then got the evidence you need for both regulatory submissions. You're right, Christian, that if you're a Korean company, you've validated your product, your technology in a Korean patient population, even more so than European, you will probably then have to re-validate in a US patient population because there are meaningful differences between Asian populations, American population, and to some degree, European patient population. So, we, we do see this frequently. Companies have to do an additional study in the US because FDA want to see technologies that they're going to approve have been tested on, on US patients. So yeah, that is common. Christian: How specific do we get? Because the demographics in, let's say, certain parts of Alabama are going to be different than certain parts of California versus certain parts of like New York. You know, a clinical research perspective, clinical study perspective. So does that matter at that level or can it just be US-based? Rob: Another good question. So, most clinical studies do collect information on race, ethnicity, sex, gender. So you do understand the type of patient that you're testing your technology in. Now, in a perfect world, you would want to demonstrate that your technology works on all different types of human beings. So all different races, all different ethnicities. But unfortunately, you have to do a clinical study that's within your small budget. So, you have to think about who is the target user for this. And if you're developing a technology that is specifically for Caucasians or specifically for Asians, you would need to demonstrate evidence for that group. If you want to expand your indication of use to include different patients, you would then have to do another study. So, typically, what manufacturers do is they recognize where do I want to launch this product, what patients do I want to treat, and then they go after those. Then, if they want to expand, they'll do another clinical study and enroll different types of patients. But this, this touches on another big thing in the clinical research industry now, which is that there's not enough diversity in clinical trials, because as I've said, companies want to target US, it's the biggest market. US is primarily comprised of white Caucasians. And so all the data is based on white Caucasians, and so there are other groups of society that, there's no data to support the use of the this device. So we're trying, we're as CRO, um, and as a clinical research professional, we're always pushing for greater diversity in clinical trials. It's just that that often collides with budget. Christian: And how do typically the patients get selected for these clinical trials? Is it a volunteer basis? Like some, they sign up for lists, like, or the manufacturer reaches out? Like how, how's that typically work? Rob: So, I think you have highlighted the greatest challenge in clinical research, which is enrollment. How do you find patients who are not only eligible for your trial, but willing to participate? Maybe they're willing to have, be treated with some technology which is untested and is not the standard of care. So, we could have an entire series of podcasts just on enrollment. So, I, I'll, I'll try and be brief. When you do a clinical study, you first start with your indication for use. What patient population am I going to treat? What is the method of treatment? What are the outcomes? And then you'll build your eligibility criteria around that because you don't want any confounding factors in there. You want it to be a perfectly controlled experiment. So you want to treat patients with the disease or the condition, and patients that don't have any other related disease or conditions that would muddy the waters and, and would give you false results, for example. So you have to have a list of eligibility criteria. Are they over the age of 18? Do they have this condition? Do they not have other conditions that would impact the data? Are they willing to participate? And then it's the responsibility of the sites to find those patients. So, when I say sites, I typically mean hospitals or it could be a clinic, a family practice. Typically, you would work with a hospital that sees lots of the patient group that you want to test your device in. And then there would be research staff at that clinic or that hospital who will then go and find those patients. So, they'll look at surgery lists, if you've got a surgical device, they'll be looking at surgery lists. They'll then approach the patient and say, "Hey, we've got a clinical trial, we think you're eligible. Here's an information sheet, it lists all the risks of associated with participating, perhaps some of the benefits. Um, are you interested? Go away, speak to your family. Let us know if you're interested." and then you sign the consent form and that's written consent. Sometimes enrollment is even more challenging and you actually actively have to go out and find these patients. And so, there are other ways you can do this. You can use promotional materials, you can have adverts, you can use social media. All of these have to be approved by an ethics committee. You can't just advertise for clinical trials on Facebook without it being approved by an, an ethics committee. So, yeah, no one's really cracked this big question of how to enroll into clinical trials because patients are willing to do research, but finding patients that meet the long list of eligibility criteria is tough. And so, I started my career at the hospitals, working with patients, and what I find is patients want to participate, they really want to altruistically give up their time to participate in research. It's just that the criteria to be able to participate are so strict that finding someone that meets all these criteria can be quite a challenge. Christian: Is it common to incentivize the patients, like monetarily? Rob: Depends what part of the world you're in. Um, so for example, here in the UK, you, you're not able to do that. You're only able to pay travel expenses. And typically, it's, it's not common. It's very uncommon to do this because you want to ensure that the patient's justification and reasoning for joining the clinical trial is because they want to participate in research, not because they want to make money because you, you don't want to ever incentivize someone from a financial point of view to participate in a clinical trial. So typically, the expenses you would see would be travel costs, maybe a meal, out of pocket costs. The exception is in pharmaceutical industry, phase one clinical trials, where, you know, you have these phase one units, it's a brand new, uh, drug, it's not been tested on human beings before. Typically they recruit healthy volunteers to, um, find out what the right dose is. And this can be quite an unpleasant experience because they just keep increasing the dose until you vomit or something. Now, those are financially incentivized. I wouldn't recommend anyone listening to this podcast to go and do that because it's quite, it can be quite an unpleasant experience. Um, but you are compensated fairly for the adversity of the experience. Christian: So, it sounds like from an enrollment perspective, that's the biggest challenge. Finding people that meet the criteria. And is it such a big challenge where certain manufacturers and innovators simply cannot run clinical studies because they can't get enough people to enroll? Rob: Yes. There are some conditions which are so rare that enrollment is almost prohibitively difficult. We were speaking with, um, an organization recently who are working on a treatment for aortic dissection, which is an acute tear in the aorta. And it's a very rare event. And so the FDA... make exceptions for this. They know that these events are rare. Enrollment is going to be extremely difficult, so they allow the sample size to be slightly lower. So, I, you wouldn't start a clinical study unless you were confident that you were able to enroll. And if it is a super rare event, super rare condition, then unfortunately, you just need more sites. You need to spend more money on having more opportunities to enroll. But yeah, frequently studies fail, manufacturers fail because enrollment fails and enrollment does not get hit on time. The study has to close and lots of technologies are ultimately not brought to market because enrollment is not successful. Christian: Awesome. Well, thanks again for joining us. I'm Rob, all the way from the UK from Brighton, I believe you said, right? Rob: Correct, yeah. Christian: Is it sunny there ever? Rob: Today, it's pretty nice. Yeah. I mean, typically, we're a gray island, but, um, for today, it's quite blue skies. It's lovely. Christian: Awesome. It's good to, when the sun comes out in, uh, the UK. Cool. Well, thanks again for joining us. And thanks everyone for tuning in to the Med Device Cyber Podcast. We hope to see you on the next one and we hope you found this one valuable. Rob: Thank you very much.