Selling a medical device in the EU? Understanding the importance of clinical data and what's required will be crucial to your success. 

In this episode of the Global Medical Device Podcast, Jon Speer and Etienne Nichols talk to Adam Steadman, Chief Commercial Officer for SMART-TRIAL, about best practices⁠—not shortcuts⁠—to bridge the gap between medical devices and clinical data.

SMART-TRIAL is an Electronic Data Capture (EDC) company that provides software as a service (SaaS). The EDC software generates, collects, and manages data used in clinical studies.

 

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Some highlights of this episode include:

  • EDC is a newer concept or discipline for the medical device industry. Compared to the pharmaceutical space, automation from the clinical trial perspective has been a bit slower because of smaller sample sizes.

  • Post-market surveillance activities are driven by EU MDR. In Europe, medical device companies are now being forced to prove to the world that their device continues to be effective against its peers and new products getting to market.

  • Pre- and post-market data is to get medical devices to market and continue to be adopted, reliable, effective, and not discontinued due to new products.

  • Another type of data that SMART-TRIAL can capture is related to payors. Does your product show an economic benefit to get reimbursed? 

  • It’s difficult to get feedback from those in the field, during tests, and clinical trials. If something’s not working, expect more feedback. If it’s working, you get less.

  • EU MDR has had two significant impacts: the number of notified bodies is still not where it needs to be and it has created rationalization of product SKUs.

  • Decentralization or remote patient care can change data results in clinical trials by using medical devices and technology to work more efficiently. For example, what’s the difference between medical device vs. health/lifestyle product data?

  • Rules are slightly different when developing algorithms and software for medical devices. They’re not written that differently and updated standards are not typically complete overhauls. 


Links:

SMART-TRIAL

Adam Steadman on LinkedIn

ISO 14155:2020

ISO 20916:2019

European Union Medical Device Regulation (EU MDR)

FDA - Medical Device Overview

FDA - 510(k) Process

FDA - Premarket Approval (PMA)

Quality is Free by Philip B. Crosby

Ultimate Guide to Clinical Evaluation of a Medical Device in the EU

True Quality 2022

Greenlight Guru YouTube Channel

MedTech True Quality Stories Podcast

Greenlight Guru

 

Memorable quotes from adam steadman:

“The device industry in terms of automating from a clinical trial perspective has been a little bit slower than the pharma side of things. One of the reasons is we have much smaller sample sizes.”

“Technology has gotten to the point now where we can do it efficiently and inexpensively at the same time.”

“What’s really happening in Europe now is that you’re being forced to prove to the world that your device continues to be effective against its peers and against other products that are coming out on the market as new products.” 

“There’s a good reason for regulation. There’s a good reason why we changed the regulations in Europe. We’ve got to have these standards for everyone’s benefit.”

“When you’re developing algorithms, when you’re developing software for medical devices, the rules are slightly different and they’re not written that differently.”

 

Transcript

Announcer: Welcome to The Global Medical Device Podcast, where today's brightest minds in the medical device industry go to get their most useful and actionable insider knowledge, direct from some of the world's leading medical device experts and companies.

Etienne Nichols: Hey everyone, welcome back to The Global Medical Device Podcast. This is Etienne Nichols, your co- host. And with me today is Jon Speer, host of the show and founder of Greenlight Guru. Today we have with us Adam Steadman, Chief Commercial Officer for Smart- Trial. So we'll talk about what Smart- Trial is and what they do, and get a little bit more into those details, but Adam, maybe we should give a little bit of introduction about what Smart- Trial is just so we can lead into some of the things we could talk about today.

Adam Steadman: Thank you very much for having me on the podcast. So Smart- Trial is an electronic data capture company. We provide software as a service and the EDC software we have is for generating data or collecting data and managing data that you may use in a clinical perspective when you're developing your devices. So we have a range of products within them. We start with very basic EDC services, and then we have ePRO and eCOA, which are basically the ability to bring patient data or to bring machine data into the database, to provide a comprehensive data solution for mid tech manufacturers developing their products.

Jon Speer: And Adam, EDC is not new, per se, but I think it is a newer concept or newer discipline for the med device industry. Can you maybe speak a little bit about that?

Adam Steadman: Sure. I think, like with many things, the device industry in terms of automating from a clinical trial perspective has been a little bit slower than the pharma side of things. One of the reasons is, we have much smaller sample sizes. With smaller sample sizes, it's easier to do things on paper than it is to automate them. And obviously as you get a bigger sample size, as you do in the pharma studies, the urgency and need to do so is. Technology's got to the point now where we can do it efficiently and inexpensively at the same time. And so it does make sense, where previously paper was the only option, because the database would cost too much money, take too much time to set up, too much programming and so forth. Today, you can figure it so much more easily than... And now it's got to the point where it really makes sense, with everything you're doing, to go electronic versus going paper.

Etienne Nichols: Yeah and I think that's compounded by some of the, obviously recent changes in the EUMDR, putting much more emphasis on clinical data and post- market clinical data, and I think just the industry in general seems to be waking up to the need to manage products for the total product life cycle and doing a better job at post- market surveillance types of activities. So yeah, it seems like now is a great time to explore this for a medical device company.

Adam Steadman: Most definitely. I mean, from our perspective, MDR has been a big driver of it because they not only require post- market safety data, but there's no requirement for post- market effectiveness data, which is unique because that's not actually required in the US either. And so for that reason, we previously had safety reporting mechanisms, well, they're not mechanisms that are going to be reporting the effectiveness of products moving forward. We've relied on market forces in the US to cover that, so we're assuming that if a better product comes in, well, the old one will die and not be adopted or be discontinued from use and so forth. But what's really happening in Europe now is that you're being forced to prove to the world that your device continues to be effective against its peers and against other products that are coming out of market as new product.

Etienne Nichols: So you kind of talked about a few different types of data, so you got your pre- market data, the things to get to market, and then post- market data. Are there ways medical devices look at data, and maybe ways they should look at data, from a CRO? Maybe you have thoughts on that?

Adam Steadman: Yeah, most definitely. I would say this, depending on how you look at things, there's either four or five different main sets of data you should be looking at as a med device manufacturer. I say four or five because you've got one extra set of data to think about if you're a software as a medical device manufacturer, if you're programming software. And really, that's algorithm development. So that's your first type of data. You've got to see that your algorithm development is working and that it's reliable and so forth. That feeds into proof of concept data, but at the end of the day, your first set of data in that situation is, well, do I have a product? And it doesn't matter about developing it. Do I have one in the first place? That's the first thing to work on. Then the next thing is really proving to yourself that you have a marketable product and getting past proof of concept. And it's not just yourself, when I talk about yourself it's you, your investors, and so forth. So we haven't even got to a regular entry submission yet or anything like that, we haven't got the pricing. We just got to the situation of, do we actually have something here? So that's the second set of data, if you like. The third set of data is your regulatory data. You obviously have to have whatever's data is required to make sure that you can get your product approved. Be it an approval or a clearance in the US, be it a C- marking in Europe, be it whatever the requirements are in Japan, Korea, China, whichever market you chose. So that's your regulatory data. And unfortunately, most manufacturers focus on that. They look at that as being the pretty much the be all and end all. It's important, but it's not the most important thing. Well, maybe it is the most important thing, but it's valueless on its own, you've got to have other sets of data with it at the same time. And so the other two major sets of data that people forget about, one is your payer data. Are your payers going to pay you? Now, people in Europe look at this somewhat differently than the States because of the different payment mechanisms. But at the end of the day, if you're in Europe, maybe you're working with NICE in the UK or the French authorities and so forth. French are very, very sticky on this. When you've got to show an economic benefit for your product. So you've got to think about these things and how do you bring in that economic benefit data into your data set so that you can get reimbursed? No good having a product in the market and not being able to get reimbursed. And then the fourth or fifth, depending on how you look at it, set of data, data that's going to get your adoption from your physicians. So if you don't have your physicians saying," Yeah, we like this new product," you're going nowhere. And I'll give you a prime example of how that can miss so badly. We had this a number of times with device manufacturers. We had one US manufacturer, I won't name who they are for obvious reasons, but they're a larger company here. And they had a not particularly good first generation product. Well known in the market, though. And what they then did is, they decided that they were going to improve the product, develop it to a much better capability, and release it and use their 510k as a predicate. Or use their existing machine as a predicate 510k pathway. For that reason, they didn't need to do clinical trials and they went ahead and they got their product to proof. They went ahead and got their product manufactured. They couldn't sell it. The reason they couldn't sell it is there was no clinical data to prove it was any better than the existing equipment that they'd already put in the market. And quite frankly, they didn't have a particularly good reputation for that equipment. So they came to us, can you now start doing clinical trials? And we started doing clinical trials for them, this is a former company, and that the method to get the data. But the thing is, they were several years late in the market, after they got their product cleared, to be able to actually sell their product. And that was just terrible. There were a few people not very happy in that organization. And had they thought the process through and thought about the needs for data right up front, when they should have been thinking about it, they wouldn't have had that. Their financial position would've been millions and millions dollars different than it is today.

Jon Speer: So you mentioned four, maybe five types of data there. Then is Smart- Trial able to capture all of that? Or how does that work? And do you assist in identifying those types of data that need to be captured?

Adam Steadman: Absolutely. We can collect any type of data that I've mentioned here. And data comes in different forms. A lot of it is your ECRF, which is your case report forms, where people take a computerized form and they complete the data on the form and they submit it that way. And that's what a clinical site typically fills in. We then have ePRO data, so your patient reported outcomes, and that kind of data is basically surveys and questionnaires. You ask a patient, how are they feeling? Do they feel better than they felt yesterday? Is the medication giving them any side effects and all these sort of things that you can only get the feedback from the patient. And then we've got what we call eCOA, clinical outcomes assessment data, and that's anything from a blood pressure monitor to an ECG machine, to some kind of wearable. So all of that kind of data can be pulled in. What we don't provide is, we don't provide the consulting service around that. That's where you need your clinical consultancies, your CROs, your experts to provide that sort of sort. But we provide them the tools that they can use to come up with those decision points and figure out what data they're going to collect, how they're going to collect, and where they're going to collect it.

Jon Speer: I think, as you described that, I mean it does, at least in my head, seem like there are certain device types that, capturing this type of data is more natural than others. I mean, my upbringing in the med device world, a lot of catheter- based technologies, purely mechanical type products with no electronics and that sort of thing. And how does a company that maybe has products like that, that don't seem to really align with data capture, especially from a benefit perspective or from a performance perspective in the field. How are they adapting this new world?

Adam Steadman: Well, I think that's an interesting question. There's a few different ways of looking at it. One thing is that many of the products traditionally were very mechanical. You talk of catheters and so forth, it's surprising how much software and how much computer support those devices have now. A lot of it will be the imaging that's tracking what's going on, but then also, operating room software and things like that that's helping guide the treatment and so forth. So there's a little bit of that. There's also a... Lost my train of thought there, I put myself off completely. Overthinking the subject.

Jon Speer: Well, I mean, let's use a different example. I know there's been some movement in orthopedics, but there again, this is an implanted product. It's predominantly mechanical in nature. I know there's been some chatter over the years about putting some sort of sensors and things on surfaces or embedded in those materials. But how does one track performance of an orthopedic type of implant? A more mechanical type product.

Adam Steadman: So you've got two sites, then. You've got the clinical trial itself and then you've got ongoing data collection, and as we discussed earlier in the discussion, the requirement for post- market effectiveness data has now been brought in. Which wasn't previously there and isn't strongly demanded in the US. So when you're looking at the clinical trial, you don't really have much of an option other than to collect site data from the site, being the operating theater or the surgeon, whatever it happens to be. The PI, if you like, in the investigation. And that's CRF captured data, pretty much all the time. What you can do is you can factor in things like human factors type studies, and that may be down to, you're using a device in a surgical situation. You need to know that you can actually sterilize the device and re-use it. So you might have a human factors test where you take 10 or 20 devices, 10 or 20 pairs of physicians, you have them clean the equipment, for instance. Then you do testing on the equipment afterwards to make sure that it has been fully sanitized. So that's one of the types of tests you can do. And a human factors test like that, absolutely, you could use the same functionality in our software. And when you're looking at post- market clinical follow up data, it's a little bit of a different situation and you've got two reasons for that. One is, you may know who your customers are. You may have a very direct way of approaching them, but what very often happens is, you don't have a direct way of approaching. You're working through a distributor base, particularly in Europe, where you've got 20- odd languages that you're dealing with, and therefore you don't have your own style because it doesn't make economic sense to have somebody who can speak every single European language. So what you tend to do, as a manufacturer, is you go to a set of distributors. When you start getting to the distributors like that, it's very hard to get close to the patient or close to the physician who's using equipment. So what we have is a solution that we call Cases, and I think it's fairly unique in the industry, where you can take a QR code, put it in with the instructions for use with the product when it goes to the patient or the clinical site, I should say. And then when they open up the package, they can do the surgery, whatever the procedure happens to be. And then they can scan the QR code with their cell phone and they can provide feedback. And the feedback may be," This thing worked beautifully, I've never had one work so well in my life." Or it could be," You know what? This thing, I'm not using this brand again. I'm going to and work out of another hospital if the won't change this for something else." You never know, but you can drive that kind of result. You can collect that data, you can report that data into your CEOs, and you can fulfill the requirements that the notified bodies have for you to maintain and continue with your C marking.

Jon Speer: That's kind of clever. I mean, those customers that have implemented that type of solution, what has the feedback been? I mean, are they getting good participation from the field, as far as people providing that sort of feedback?

Adam Steadman: Yeah, they are. I mean, it's always relative. When you're looking at physicians, their time is busy. I mean, it's hard to get feedback. The good thing that you do know about them is, it's kind of that eight to one principle of, you do something bad, you'll hear eight complaints. You do something good, you hear one compliment. It's kind of the same principle. If something's not working in the field, you are going to get the feedback. If it's working well, you may get less feedback. And that's just a human nature kind of problem that you've got to deal with.

Etienne Nichols: Yeah, for sure.

Jon Speer: And I think it's interesting, too, I mean you talked about the European model, obviously it happens to some extent here in the United States too, but the reliance or the dependence on distributors. I mean, that's a much bigger thing in the EU marketplace than it is in the US for many of the reasons that you stated. And then historically, there haven't been a lot of controls or oversight on distributors. And I know with the EUMDR obviously they expanded the definition of economic operators and the expectations and criteria for adhering to the regulations. I'm curious too, have we seen a fallout? It's a little off topic, but have we seen a fallout of the number of distributors in the European marketplace because of the new requirements in the EU?

Adam Steadman: I haven't. I haven't specifically. I don't think I've been that close enough to the commercial side of many of these things. But what's interesting when you talk about pullout is, we look at two things that have been impacted significantly by the MDR on that. One is the number of notified bodies. There's still any two or three notified bodies that can do plus three active implant devices, which is terrible. I mean, it really limits things. And then the other thing to think about is, MDR has created a lot of rationalization of the process they use. I was talking to one large manufacturer a couple of years ago, and they had 144,000 SKUs in their imagery. Now that's not 144, 000 different products, to be clear. That was about 2000 products with different packages, different sizes, different country, languages and all this sort of thing, making it. But they figured they were going to probably cut that down to 50 or 60,000 SKUs. What that guarantees is that there's a lot of product gone off the market. A lot of the historical products that may be marginal in certain territories, they'll take it out. It doesn't justify the cost of making or meeting the MDR regulations. So it'd be interesting to actually see. We're eight months in, nine months in, I think COVID has bent everything out of shape in terms of stats. So making a comparison in the last eight months versus the eight months prior wouldn't be sensible. But it will be interesting to see in the next couple years how that has impacted manufacturers.

Jon Speer: For sure. You also mentioned the criteria of measuring the economic benefit. And obviously every device has probably a variety of different methodologies and techniques to demonstrate that. But has the EU defined certain thresholds or expected behaviors or criteria around the expected benefit? Has that been defined or is that up to the manufacturer to define that?

Adam Steadman: I think it's a combination of, it's not part of the MDR, so, yeah, responsibility is on the manufacturer to demonstrate it. But that is more to the local national bodies, like NICE in the UK, that are making those evaluations. So they're looking at it from an economic perspective saying," Is this better?" I mean, you may have seen them, as I have, I've seen so many investor presentations where they say," Well, we can reduce time in the operating theater by an average of 42 minutes." Or,"We can reduce hospital stays by three days." Well, that's a great thing to say. You've got to prove it, nobody's just going to accept that. You've got to prove it, you've got to have it in peer reviewed documentation, you've got to have written several articles, you've got to have done randomized clinical trials. There's all sorts of requirements to think about if you actually want really maximize your ability to sell your products and get paid for them.

Jon Speer: Yeah, that's good food for thought.

Etienne Nichols: When the pandemic first hit, I worked with a company, I'm trying to remember the exact company. Guess that doesn't matter. They were trying to do an in- home study with... They couldn't go there themselves, like maybe they would've previously. They were thinking about sending a webcam or so forth. Have you seen the data or the results of that, maybe human factors as you mentioned, be different because maybe the studies would've been performed one way previously, but now things have changed. Now we're performing them maybe a different way?

Adam Steadman: Things like that, but I don't think it'll be a long term because essentially, the question is... We'll hear one of the buzzwords in the industry at the moment is decentralized clinical trials. Probably the biggest buzzword. And then following close on the heels of that is DTP, direct to patient. And really what they're talking about there is, let's make it easier for the patient. We'll go to them, they don't have to come to us well. Well, that's great if you are sending FedEx to your home with drug supply, doing a clinical trial along that basis, and then you have a telehealth meeting and you say," How are you feeling? Were you sick? Did you have any after effects?" The doctor can talk to the patient on a telehealth basis. You can't really do that with devices, particularly where they're implantable. At the end of the day, when we do device studies, most of what we do with the device study is a one and done. It's a, go into the hospital, the clinic, the ambulatory surgical center, you get the device implanted, whatever it happens to be. And you'll have maybe a couple of follow- ups, but it's one and done. Generally. The drug world's very different. So if you've got one and done, you've got to come into the site anyhow. So what we can do is we can start looking at way more efficient ways of helping patients, where we can do things like follow up visits in those clinical trials remotely. So the follow- up visits could be remote instead of having to come into the site to have your blood pressure taken, weigh yourself, check that your height hasn't changed. They always seem to check that, I have no idea why because most of us don't shrink too much in six months. But at the end of the day, we can a lot of technologies that are sensible to use because they're more efficient, but that doesn't necessarily mean we can change the way we do some of these things. And a prime example of that is eConsent, eConsent wasn't very well accepted or common prior to the pandemic, and a lot of people think of eConsent as being a remote consented procedure. And a lot of people don't think that's real because you don't want somebody just to click a check box saying yeah, they consent, without understanding. The whole idea is, you're supposed to sit with a physician, talk with them, understand it. Physician's supposed to explain it to you, and based on your understanding, you then make an informed decision. That's the whole concept, you can see. So there's been a lot of resistance to eConsent. Well, I don't want somebody just clicking I agree or I accept box as you do when downloading software on your computer or opening your bank account or something like that. But the point is, if your physician is sitting opposite you and you have that same discussion that you would've had, but you click a button, having scanned your QR code on your phone or something, for instance, then you've electronically recorded consent. That's just joining the modern world. We now have something that we can remotely monitor, we don't have to go to the site and check consent, we can remotely monitor that. We can check that 100% of the patients in the study are consented. So just doing things like that. They're driven by the pandemic, they're not necessarily needed to take people at home, but it's just a better technology. A better way of doing things in the future. And I think that's, it's sad to say this, there are some good things that came out of the pandemic. Sadly, not many, but some of the things, we're thinking smarter about how we're doing things these days.

Etienne Nichols: Yeah, that makes sense. Go ahead, Jon.

Jon Speer: I was going to say, I think there's quite a few things that have come out of... I think, to your point, working more efficiently, a little bit more intelligent. I think that's key. Because I think a lot of companies got so, I guess complacent's probably a good word, in a way of doing business. It was almost just, like those products that needed clinical studies, for example, I mean, I think there was an accepted methodology and approach. And I think a lot of times that maybe we should have been thinking a little bit more critically about how to do that. And I think going through the pandemic has forced a lot of companies to think a little bit differently. I like the idea that Etienne mentioned, some of these companies maybe thought, hey, maybe we need to send a webcam with this so we can make sure that this is being used properly. But I think we're in an era where so many products that we use in our everyday lives. I mean, I don't have any on my wrist, but a lot of people are wearing things on their wrists that are telling them things about their sleep and their heart rate and all these sorts of things. I mean, the lines are very blurry and fuzzy between what is and is not a medical device. And there's data being collected everywhere, but somebody's got to make sense of all this.

Adam Steadman: Yeah, I think that's an area that also needs a lot of improvement. There is a, to your point, a very blurry line between what's medical data and what's just health and lifestyle data. And I was at CES a short while ago, looked at a couple of the devices they had there, and I had Sp02 meter measure me and it said I had a 92 as an Sp02. I should have been in an ambulance on the way to the hospital if that was true. And then they're equally... Their blood pressure monitor, their wrist- based blood pressure monitor said my blood pressure was 165 over 125. Likewise, I would've been in an ambulance on the way to the hospital. In fact, probably at 125, at best I'd probably be dead, to be honest. So yeah, it's kind of scary when you think that products like that, because they've being sold as informative healthcare lifestyle products instead of true medical devices. There's a good reason for regulation. There's a good reason why we changed the regulations in Europe, because we've got to have these standards for everyone's benefit.

Etienne Nichols: And that makes a lot of sense. I'm not going to talk about the wearable I'm wearing now. So I do want to ask you, you talked about some different ways to collect data. Do you have any maybe best practices for manufacturers? And I'd also, maybe we can make this a two- part question, if you could maybe deal with software as a medical device separately. If it is separate. Any thoughts there?

Adam Steadman: Sure. Best practices. Well, let's talk about wearables in general here. And we often talk about wearables, but wearables include a couple of things that aren't wearable, like scales to weigh yourself on. You can't really wear that, but we'll assume that's in the same area. So the first thing is, when you're running algorithm development trials, you should loosen up on sticking to the accepted norms for traditional device development. And what I mean by that is, certain areas in the device world, you've got ISO standards, which drive how you measure and how you compare devices. I'll give you an example, if you take a ambulatory blood pressure monitoring device, there's a standard ISO procedure... Or any blood pressure monitoring device for that matter, a standard procedure that says you do this procedure 30 times over and you do it with three observers, using simultaneously and all the rest of it. Well, if you're developing an algorithm, you don't have to follow the ISO standard to develop the algorithm. You need the ISO standard to validate the product. And we've now seen this, where big companies have tried to apply that same ISO standard complexity and depth of what they're doing to massive populations. Trying to get 10, 000 patients into overnight stays to see if your watch works is not a very efficient way of developing an algorithm. And I've seen that. So I think the first thing is, just remember when you're developing algorithms, when you're developing software for medical devices, the rules are slightly different. And they're not written that differently, unfortunately. So it's not blatantly obvious when you go look at the IMDF suggestions or regulations. If you look at the FDA regulations, if you look at the MDR, it's not clear in any of those how you should do that. And the ISO standards themselves, there's very few ISO standards that are written with today's technology in mind. And just an example of that, when you think about technology and how quickly it changes, think of the development scope that's had. And half of the regulations we work off of are older than that. So when you look at standards, even if they've been updated, very often they're not complete overhauls, they're tweaks and changes and so forth. And sometimes we need to look at things, particularly when you're looking at software development, algorithm development, you've got to look at it and say," Am I being realistic? Am I really, truly doing what I need to, to obtain the data that I need, to get the assurance I need?" And the first thing is, take the data, make sure your algorithm is square, then do a confirmatory test on your algorithm, to make sure you're in line with where you need to be, and then do your regulatory, pivotal trial. I've seen companies trying to skip steps. And that's not good. Trying to use your algorithm development data for a pivotal trial, trying to combine them as one, that's not a very good plan. And fortunately, a lot of that stuff is 510k, so you're not getting that. But then having said fortunately, if you're not developing it the right way, it's not fortunate for a patient. So the regulations may allow you to do it, but the best practice is what you should always follow. The patient safety's got to be the number one consideration every step of the way, for every single device, every single person developing one.

Etienne Nichols: Just going back to what you were saying... Sorry, Jon.

Jon Speer: No, go ahead.

Etienne Nichols: The feasibility data and your regulatory data, you also are still going to need that adoption data, like you were saying, if you really want your product to be adopted. Go ahead, Jon.

Jon Speer: I just want to go back to remind folks, I mean, what you were speaking about with respect to of standards and algorithm development. I just want to emphasize that because standards don't necessarily represent state of the art thinking because of the time, effort, and energy, and resources and committees and all those sorts of things that standards have to go through in order to get published. They were represent a moment in time of what is acceptable or potentially expected. But if you have a product that is a variant or differs from the scope of some of these standards, heed what Adam is saying, use those as maybe for some guiding principles. But not in an absolute sort of way, in a vacuum. And I think the other thing that a lot of folks listening may be thinking is, well, I need the regulators to tell me what I need to do. And if you feel that way, because you have a device where a standard doesn't necessarily fit, be careful what you ask for. Because if you ask the regulators to tell you what thou shalt do, they will. And it's likely to be a pretty extreme version of what you were thinking. Because again, keep in mind, the role of the regulator is to ensure the product that gets onto marketplace is as safe as it could possibly be. So in order to demonstrate that, if you ask the question open- endedly, you may not like the answer. You may be told," Oh yeah, you need to do a 50, 000 patient randomized, blah, blah, blah, double arm, double blind study," or whatever the case may be. So my advice to you is, come to the regulator. We have this opportunity in the United States through a pre- submission, come to them with your plan. Lead the conversation, don't just blindly ask and hope that the regulators tell you what you need to do. So just think a little bit critically about that.

Adam Steadman: 100%. Couldn't agree more. And unfortunately, we have seen examples of people doing the wrong thing there. And then, to your point, once you ask the FDA something, and they tell you've got to do it, it's very, very hard to turn around on that. And one of the big changes with the regulations in Europe, which is aligned to that, is prior to the MDR, the notified body could be your consultant. So that consultant would tell you what you needed to do and you relied on that, to some degree. And then, of course, you would go to them and you'd have them verify things. And you can understand where the conflict of interest comes in there. They're telling you how to do it, and then you've met all their requirements, but they're not happy with it. Well, they can't say we're not happy with it, they've got to say," Well, you didn't do what we told you to do." So there's a real conflict there, which is now very clear in the new regulations you can't have. So you don't even have that opportunity now, unfortunately in Europe, to go and ask the notified body how to do it. You can say," This is my plan, do you agree with my plan?" And they'll say yes or no, but they can't guide you or advise you and so forth. So very much changing times, no doubt about it.

Etienne Nichols: I love what you said, Jon, about that. Made me think of, at one point in my career, I heard somebody... I think they were quoting Phil Crosby, the author of Quality is Free, they said," Quality is conformance to the standard," but in certain situations, we should probably go a little further and build quality in ourselves. We kind of cut off a little bit, Adam, we talked a little bit about the software. Did you have best practices in general or did we cover that? I mean, are we good?

Adam Steadman: Yeah, I focus very much on software as medical devices there, but best practices in general, I think number one best practice that companies should not forget about is, make sure you follow ISO 14155- 2020. That is the GCP standard for medical devices. And then if you are a diagnostic manufacturer it's ISO 20916- 2019. And do not use the GCP for drug, ICH- GCP, unless you're using a combination product, and then you should make sure you apply to both. And quite frankly, as they've developed these standards, they have got a lot closer to each other. A few years back ISO 14155-2011 was quite different from ICH- GCP. But that comes with so many things that are so essential when you are doing clinical trials. And that really does need to be followed. So I think that's an invaluable requirement, if you like. But having said that, you must know how many times people don't... Prime example, you need consent to do any kind of medical trial with people. The number of times we see small companies have just started, they got a new product and you say," Well, how do you know it's going to work?" Well, I've already used it and this person, this person, this person, my auntie. Well, you're not allowed to use it on your auntie or yourself or any other human subject without going through the proper procedures and following the proper compliance and so forth. And it's easy to be tempted to not follow those standards, but you need to. And then the other is, just make sure you meet all of the regulatory requirements. Don't slip past and do your clinical trial and hope to get away with not having the insurance you need and things like that. You have a lot of regulatory rules, make sure that you've understood them, that you've followed them, and that you've complied. And unfortunately, particularly in the software world, as your organization knows from developing software, you've got to have a trail going right back to day one, showing how you got to where you have today. All these basic quality requirements you've got. You get an FDA biomed audit, the biomedical monitoring audit, which you have to have if you have a PMA submission, they're going to look at files like that. They're going to look at your design files and so forth and make sure that you've done what you have to do from day one. So best practice, don't take shortcuts. They bite you where you don't need to be bitten later. Always. It's just not worth taking shortcuts.

Jon Speer: Yeah, I just felt a little triggered and I'll explain why, but before I explain that, Adam, can you... I know these are second nature, back of the hand, easy for you to remember. But you rattled those ISO standard numbers off really quickly. Can you maybe mention those again? And Etienne, it's probably good if you mention those in the notes that go in the show note. Or that accompany of the show.

Adam Steadman: Sure. So the good clinical practice, and I'll read it from the cover because I have the books right in front of me here, sitting on my desk. I didn't know what the number was, by the way. I didn't have to prove. But the actual title is Clinical Investigation of Medical Devices for Human subjects, good clinical practice. That's ISO 14155 and that came out in 2020. And then you also have pretty much the same thing, I can't find it here because I've got all my other standards in the way, and my MDR documents and so forth. ISO 20916- 2019, In Vitro Diagnostic Medical Devices, clinical performance studies using specimens from human subjects. Good study.

Jon Speer: Okay. That's great, thank you for mentioning that. And now the part that I got a little triggered about. So tell us with a short story, and I don't know if this is still commonplace, I suspect that it probably is, unfortunately. But a lot of startups, especially on this quest for first in human studies or first in human use of their product. And the particular issue that comes to mind, there was a company, they were basically pursuing first in human studies somewhere where the regulatory environment is much more lax than, say, the Europe or United States. And they were doing this before they had really defined the product and before they had defined the requirements and before they had done a risk assessment and all these sorts of things. And I think the primary motivation for them was, first in human represented an important milestone that meant that they could potentially obtain additional investment to keep their company growing and going and that sort of thing. But there's so many holes in that approach. To your point, if you want to do that, great. Just don't take it as a shortcut, make sure that you're following expected best practices and good design philosophy, good design control, good risk management and that sort of thing. But sadly, I see way too many companies trying to cut that corner, just jump to the end. Jump to the human use of their product.

Adam Steadman: Yeah. So there's two sides to that, I think. On one side of it, I've seen companies going to South America and so forth, and they'll tell you honestly," Well, the reason we're going there is if something goes wrong, it's not going to get reported in the press. We're not going to be associated with it." That's the absolute worst reason to do it in another country, as far as I'm concerned. And to be honest, companies that do that and risk things too far and make it obvious what they've done, they will get nailed by the foreign authorities. And there have been cases of that happening. But what I would hate to say is that people shouldn't go to other countries. A lot of the countries in Latin America, you could go to a country, you could go to Columbia, you could go to Peru, you can go to Argentina or Brazil. I mean, Brazil's got probably the strongest regulator there, but they all have good regulatory infrastructure. But I think what's more important is you've got a phenomenal depth of doctors there, who have real, sound, scientific expertise. And if you think about it, say you're trying to develop a new heart valve. Well, it's not like there aren't many heart valves out there already, there's at least four or five major manufacturers of heart valves. There's a good tale of startups in that space as well. Well, the problem is, to get a physician who's an expert to take on your product as an investigational product is not easy. You can't go to any major clinic in the US and expect them to do that because they have good products that work from major manufacturers that have been through years of clinical trials. So you're not going to get them to switch and go to something experimental. So how do you get that? You've got to go to a very competent doctor in a location that's underserved, so they don't have these preexisting supply chains of devices that are competing with yours, so that you are adding benefit to the local community because you're providing something that they can't get there already. And you're not competing against somebody who's only reason to be in a clinical study is because he wants to have his name first on the paper. They write about it and he's got all the politics that go on with his organization. So, there's different ways to look at these things, and unfortunately, as I said at the beginning, there can be bad reasons to go into these countries. But on the other hand, there's really good, practical, sensible reasons for doing it. That's why I said the number one thing to follow is ISO 14155. It's all in there. If you're following ISO 14155, you could do it anywhere in the world and not be concerned.

Jon Speer: I know on the clinical side of things, I mean, this has been evolving pretty much throughout my entire career. But sometimes it seems as though a regulatory body in one geography is not all that accepting of clinical data that is gathered in a completely different geography. Have we made progress on this in the industry in the past decade or so?

Adam Steadman: In some respect, yes, and in some respects, no. I think there is a... I mean it used to be considered the FDA would only accept US data. Well, the FDA has always said that's not the case. And I think it's only been more recently that we've seen more examples of foreign data being used to a higher degree. The FDA's requirement is that it needs to be tested in a comparable population, with a comparable standard of care, and that's what people forget. It's the standard of care that's different. If you're treating a patient differently in every other respect isn't going to operate in the same way. So I think there's legitimate reasons for saying no, we can't use data. One of the examples that the FDA quotes, that they had there for instance, was that a left ventricular assist device, which is basically a heart pump that came from Korea, had been tested in the Korean population and they wanted to use it in the States and they wanted to use the data from that. And the FDA said, no. Why? Well, the average weight of a Korean may be 120 pounds and for an American it's 220 pounds. There's a lot more pressure on their system. Can the heart pump do the same work when you look at average weights of that nature and so forth. So there is good reason for that. I think what's changed though, now, is we used to have a situation where it made sense to go to Europe and do your studies first. Or at least go to Europe, get your C- marking, and then come to the US and do your studies in the US later and take time. That whole dynamic has now changed. And what's actually happened with that dynamic is that, very often now, you may as well do your study in the US because in the US you're going to get an expectation of having US study data. There is nothing in the European regulations that requires that your data comes out of Europe. So you can use your US study data to meet the needs and requirements of your MDR and your C- marking, which, it doesn't work the other way around. And what's interesting is, I haven't seen a lot of commentary, I haven't seen a lot of comments about the impact that's going to have on the industry. But if you think about that, over time, if five years ago or so, we were planning to launch products in Europe and then come to the States later, but now we're doing it the other way around. First of all, it means that those products aren't getting into Europe as early as they used to be. So they're not quite on the forefront as where that had been, which isn't necessarily a bad thing, because they're on the forefront with relatively untested products. And maybe that's done Europe a big favor in that respect. But if you now shift a lot of that primary clinical work to the US, done in Europe, what is the impact that could be on the research institutions in Europe? Does that mean your research hospitals are going to get less and less studies going there? Less and less innovation going there? How is that going to impact Europe as a whole? And that's one of the questions I haven't seen asked anywhere. That's downside of the MDR that I haven't heard anyone talking about.

Jon Speer: That's very interesting, because I hadn't thought about it from that lens, but there's a lot of research institutions that, that's what they do. They're cutting edge, their mission, their reason for existence is to investigate cutting edge technologies and products to improve healthcare. And if that's not coming through their system anymore, then yeah, it's a great question. Unfortunately with, not at least as we know it here today, and not a so positive outcome or outlook anyway.

Adam Steadman: Indeed. And I think one of the other things to remember is a lot of hospitals supplement the services they provide, that are funded at state level, with research dollars. Which help them to provide a little bit better standard of service to their patients.

Jon Speer: Yeah, and then not to mention specialists, where are they going to practice? If their facility is not on the cutting edge with a particular technology, in a particular area of expertise of theirs, I mean, there's going to be a migration of folks. Either you're going to lose specialists in the EU and they're going to move to the US or... There's just a lot of other side effects. It's really going to be interesting. I mean, hopefully we don't have to see the negative sides of things like this, but it is, to your point, it's a question that I haven't heard asked either. Definitely not answered and I don't think a lot of people are asking this question.

Adam Steadman: Yeah, I'd be surprised if there weren't institutions in Europe already feeling it. And the thing is, COVID is going to mask a lot of things. At the moment, you're not doing clinical work in many places in Europe because of COVID. Well, is it really because of COVID? If COVID wasn't there, what would've been the impact?

Jon Speer: Yeah. I would say probably in 2020, and most of 2021, COVID was the easy, obvious excuse as to why. But at this point in 2022, I mean... And not to trivialize or minimal lives, what's still happening with COVID, but a lot of sectors of the med device industry are pretty much back to normal, in a manner of speaking. Or at least on that path. So yeah, if there's still a decline in clinical research and studies happening in Europe, then it's probably not COVID in 2022.

Adam Steadman: Exactly. Exactly.

Etienne Nichols: I don't have any follow questions, Jon. Adam, did you have anything you wanted to close out with or how we can find you? Any last pieces of advice?

Adam Steadman: Now you got me thinking. I think, just to recap on a couple of the main points, don't forget your data. Don't forget the importance of your data. Number of times I've seen with claims made on them that, you look at the claim and you think, you can't make that claim unless you've done the investigation. Be it an early payer assessment, be it more indepth clinicals, but have you thought of it all and have you done it efficiently? And that's what we see more often than not, people try to shoe string their operations along to get to the next series of funding, or whatever it is. If you can go and ask for 10 million dollars versus 15, you might choose 10 because you might say," Well, if I do 10, I'm diluting it less, I'm keeping more of the company." But at the end of the day, if it's going to then take you two more years to get your product on the market, because you took a shortcut and didn't do the additional bit of trial work you should have done at the time, you're really cutting off your nose to spite your face. And so my advice to people is, think very carefully about what you've got to do. Make sure you think about all your data streams and where you're going to get that data from. Be careful with your consultants, because I've seen consultants advising things that make no sense. And that doesn't mean there's bad consultants, there's a lot of really, really good consultants. Just make sure that you are confident with your consultants. If you have any doubts, get a second opinion, spend a little bit more money on getting that second opinion. But make sure you're getting the right data. Get the right data, manage the data properly, collect it properly, collect it with all the standards and the compliances required. Particularly if you're going PMA route, because if you're going PMA route, you've got a biomed audit coming. If you've got a biomed audit, they're looking at everything. Or at least they can look at everything. So just don't take shortcuts, do it properly, follow the standards, and do good science and develop good products.

Jon Speer: Yeah. To piggyback on what Adam's sharing, I mean, I think if you've been a listener to The Global Medical Device Podcast for any period of time, you probably have heard us talk about quality strategy and regulatory strategy. To me, clinical strategy, it's probably always been important but I think it's, in this day and age of the medical device industry, it's more important than it ever has been. And probably as important as other business strategies that you're defining as well. In an ideal world, your regulatory quality, clinical, and overall business strategy, they need to be harmonious with one another too. But the rules have changed, the expectations have changed and will continue to evolve. I mean, there's going to continue to be more emphasis put on device manufacturers to constantly show and demonstrate that their products work. And that they're effective. And that they're safe. And, as Adam has shared today, one of the only ways to be able to do that is to be continually collecting data on the performance of your products. So figure that out and start to incorporate that, get ahead of it, lean into it. And certainly, Smart- Trial is a company that has built a platform to help you with that. So I would encourage you to go visit their website. I believe, Adam, it's smart- trial.com, if I recall, right?

Adam Steadman: That is correct, yes.

Jon Speer: Yeah. So they've built a SaaS platform to help you with many of your EDC needs in the med device space. So yeah, go check it out, smart- trial. com. So, Etienne, probably a good place to put a wrapper on things today.

Etienne Nichols: Yeah, sure. Those of you who have been listening, we'll include a few of these things in our show notes. So the standards 14155, 20916, hopefully got them right, but the show notes will be correct with links so you'll have those. Like Jon mentioned, if you're interested more in hearing about Smart- Trial, or Smart- Trial, it's the Smart- Trial, we'll put that link in the notes as well so you'll be able to find that. You've been listening to The Global Medical Device Podcast, it was a great conversation, I really appreciate it. Thank you, Adam, for a great conversation. Stimulating a lot of thought and giving a lot of great, great pointers and things that we need to be thinking about and doing. For those of you who have been listening, this is powered by greenlight. guru, the only medical device success platform specifically designed for medical devices. If you're interested in learning more about that software and how it can help you get to market faster, more efficiently, and to build safe and effective products, go to www.greenlight.guru. Thanks and we'll see you next time.

Adam Steadman: Very cool, thank you everybody.


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