Bridging the Gap between Medical Devices and Clinical Data

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 Greenlight Guru Clinical (formerly SMART-TRIAL), about best practices⁠—not shortcuts⁠—to bridge the gap between medical devices and clinical data.

Greenlight Guru Clinical 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 Greenlight Guru Clinical 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:

Greenlight Guru Clinical

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:

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, also 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, do you want to talk about direct.

Just, you know, some of the. Well, maybe we should give a little bit of introduction to what Smart Trial is, just so we can lead into, you know, some of the things we could talk about today.

Adam Steadman: Fantastic. Thank you, Etienne. And good to see you as well, Jon.

So today we so hate doing this kind of thing because I blow it every time because I'm overthinking what I'm doing.

Let's just hope you can cut it. Cut that without a problem.

Jon Speer: We'll be fine.

Etienne Nichols: Yeah, yeah.

Adam Steadman: Hey, Etienne. Hi, Jon.

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 that.

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 in machine data into the database to provide a comprehensive data solution for MedTech manufacturers developing their products.

Okay.

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 and smaller sample sizes. It's easier to do things on paper than it is to automate them. And obviously, as you get bigger sample sizes you do in the pharma studies, the urgency and need to do so is greater.

Technology has 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 configure it so much more easily than.

And now it's got to the point where it really makes sense, you're doing to go electronic versus going paper.

Jon Speer: Yeah, and I, and I think that's compounded by some of the, you know, obviously recent changes in the EU MDR 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 lifecycle 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 now a requirement for post market effectiveness data which is unique because that's not actually required in the US and so for that reason, you know, we put it, you know, 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 sort of relied in market forces in the US to cover that.

So, we're assuming that better product comes in well, the old one will die and not, not be adopted or not, you know, 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 in the market as new products.

Etienne Nichols: So, so you, you kind of talked about a little, 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, are there ways medical devices look at data and maybe ways they should look at data, you know, from a CRO maybe. You have thoughts on that?

Adam Steadman: 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 mid-device manufacturer.

I say four or five because you've got one extra set of data to think about. If your software is a medical device manufacturer, if you're programming software and that's 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. It kind of 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?

It doesn't matter about developing it, do I have one in the first place? That's the first thing to work out.

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, you, your investors and so forth.

So, we haven't even got to a regulatory submission yet or anything like that. Then we've got pricing, we just got to the situation of do we actually have something here?

So, you know, 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 data is required to make sure that you can get your products approved, be it an approval or a clearance in the us, be it a CE marking in Europe, be it, you know, whatever the requirements are in Japan, Korea, China, which give them up.

So that's your regulatory data. And unfortunately, most manufacturers focus on that. They look at that as being pretty much the be all and end all.

It's important, but it's not the most important thing.

Maybe it's the most important thing, but it's valueless on its own. 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 and UK or the French authorities and so forth.

French are very, very sticky on this, where you've got to show an economic benefit to your product. So, you've got to think about these things and how do you bring in that economic benefit data into your, into your data set so that you can get reimbursed.

Having a product in the market not being able to get reimbursed, and then the fourth or fifth, depending on how you look at a set of data, that you really need to be the 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, device manufacturers.

We had one US manufacturer, I wouldn't name who they are for obvious reasons, but they're a large, larger company here and they Had a not particularly good first-generation product and hemisphere well known in the market.

And what they then did is they decided that they're going to increase the product, develop it to a much better capability and release it and use their 510k as a predicate or use the existing machine as a predicate.510(k) pathway.

For that reason, they didn't need to do clinical trials, and they went ahead, and they got their product approved, 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 on the market. And quite frankly, they didn't have a particularly good reputation for that equipment.

So, they came to us and said, can you now start doing clinical trials? And we started doing clinical trials for them. This isn't a former company, and you know, that was 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 the product. And that was just terrible.

There were a few people not very happy in that organization.

And you know, 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 have been millions and millions of dollars different than it is today.

Etienne Nichols: So does Smart Trial, is it able, 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: So absolutely, we can collect data, any type of data that I've mentioned.

And data comes in different forms.

A lot of it is your basic EDC, which is your, or sorry, 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 they feel, do they feel better than they felt yesterday, is the medication giving them any side effects, and all these sorts 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 a, you know, some kind of a 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 that's where you need your clinical consultancies, your CROs, your experts to provide that sort of support.

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.

Jon Speer: I think, you know, as you described that, I mean it does at least in my head seem like there are certain device types that where this type of 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 to sort of this new world?

Adam Steadman: Well, I think that's an interesting question. There’re a few different ways of looking at it.

One thing is that many of the products that traditionally were very mechanical, you talked to Carthages 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 the operating room software and things like that is helping guide the treatment. And so, so there's a little bit of that.

There's also a lost my train of thought then I put myself off completely overthinking the subject.

Jon Speer: Well, I mean, but let's use a different example. I mean I know there's been some movement in like orthopedics, but you know, 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 you know, how does one track performance of an orthopedic type of implant, you know, a more mechanical type of 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 affectedness 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 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 reuse it. So, you might have human factors test where you take 10 or 20 devices, 10 or 20 pairs of physicians, you have them clean the equipment, for instance, and 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 in human factors test like that? Absolutely. You could use the same functionality in our software. When you're looking at post market clinical follow up data, it's a little bit of a different situation.

You've got two reasons for that. One is you may know who your customers are, you may know, 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 distributed base, particularly in Europe when you've got, you know, 20 odd languages that you're dealing with and therefore you don't have your own stuff 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 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, in the industry where you can take a QR code, put it in with the leaflet, in with the instructions for use with the product, when it goes to the site, 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 a 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 go and work out of another hospital if I want to change this for somebody else.

You never know, you know, but you, 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 CE mark.

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

Adam Steadman: Yeah, they are. I mean, it's always relative. You know, when you're looking at positions, their time is busy. I mean, it's hard to get feedback. The good thing that you do know about them is, you know, 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're going to get feedback. If it's working well, you may get less feedback.

And you know, that's, that's just a human nature kind of problem that you've got to deal with.

Jon Speer: Yeah, for sure, for sure.

And I think it's interesting too. I mean, you talked about sort of the European model. You know, obviously there's, you know, 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 I know historically there haven't been a lot of controls or oversight on distributors. And I know with EU MDR, 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 fallout is, you know, we look at two things that have been impacted significantly by the MDR are that one is the number of notified bodies is still nowhere near where it needs to be.

There’re still only two or three notified bodies that can do, plus three implantable active implantable 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 across SKUs.

I was talking to one large manufacturer a couple of years ago and they had 144,000 SKUs in their inventory. Now that's not 144,000 different products. Products to be clear, that was about 2,000 products with different packages, different sizes, different labeling, 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 guarantee is that there's a lot of products coming up the market.

A lot of the sort of historical products may be marginal in certain territories. They'll take it out. It doesn't justify the cost of making or meet the MDR regulations.

So, it'd be interesting to actually see we're eight months in, nine months in. I think Covid has kind of bent everything out of shape in terms of stats.

So, making a comparison the last eight months versus the eight months prior wouldn't be sensible.

But it'll be interesting to see in the next couple of years how that has impacted manufacturers for sure.

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

Adam Steadman: I think, I think it's a combination of, it's not part of the MDR.

So yeah, responsibilities on the manufacturer to demonstrate it. But that is more to the local national bodies like NICE in 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, in the operating theater by an average of 42 minutes or you can reduce hospital stays by three days.

Well, that's 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 know, you've got to have written several articles, you've got to have done randomized clinical trials. There’re all sorts of requirements to think about there. If you actually want to really maximize your ability to sell your products and get paid for them.

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

Etienne Nichols: When I was, when the pandemic first hit, I was, I worked with a company trying to remember the exact company. Guess that doesn't matter.

They were trying to do an in-home study where with you they couldn't go there. Themselves, like maybe they would have, you know, previously they were thinking about sending a webcam or so forth.

Have you seen or have you seen the data or, or the, the results of that? Like maybe human factors you mentioned be different because maybe the studies would have been performed one way previously, but now things have changed.

Now we're performing them maybe a different way.

Adam Steadman: Impact things like that. But I don't think it'll be a long term because essentially the question there's. You'll hear one of the buzzwords in the industry at the moment, decentralized clinical trials, probably the biggest buzzword and then sort of following close on the, on the heels of that is DTP direct patient.

And really what they're talking about there is let's make it easier for the patient. You know, we'll go to them, they don't have to come to us. Well, that's great.

If you're sending FedEx to your home with drug supply, doing a clinical trial on that basis and then you have a telehealth meeting, 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 with 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, so if you've got one, um, done, you've got to come into the, 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 you know, at the end of the day we can a lot of technologies that are sensible to use because they just, 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 e-consent, e-consent wasn't very well accepted or common prior to the pandemic and a lot of people think of e-consent as being a remote consenting procedure.

A lot of people don't think that's real because, you know, you don't want so many checking for saying, yeah, they consent to without understanding it. The whole idea is you're supposed to sit with the physician, talk with them, understand it.

This physician's supposed to explain it to you. And based on your understanding, you then make an informed decision. That's the whole concept of consent.

So, there's been a lot of resistance to E consent. Well, I don't want somebody just clicking the I agree, or I accept box as you do when you are downloading software on your computer, entering 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 have had, but you click a button, having scanned your QR code on your phone or, for instance, then you've electronically recorded consent. And 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 pandemic. Sadly, not many, but some of the things, you know, we're thinking smarter about how we're doing things these days.

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

Jon Speer: I was gonna say, I think there's quite a few things that have come out of it, I think, to your point, you know, working more efficiently, a little bit more intelligently, I think. I think that's key. I mean, because I think, you know, a lot of products I got so. Or a lot of companies got so sort of, I guess complacent is probably a good word in. In a way of doing business, that it was almost just, you know, like those products that needed clinical studies, for example. I mean, I think there's. There was a sort of an accepted methodology and approach.

And I. I think a lot of times that maybe there. We should have been thinking a little bit more critically about how to do that. And I think, you know, going through the pandemic has forced a lot of companies to think a little bit differently.

I like the idea that Atiya mentioned. You know, some of these companies may 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, you know, it's, we're, we're in an era where so many products like that we use in our everyday lives. I mean like 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, you know, 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 you know, somebody's got to make sense of all this, you know.

Adam Steadman: Yeah, I mean 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 beta and what's just health and lifestyle date.

And you know, I was at CES a short while ago and looked at a couple of the devices they had there. I had an SpO2 meter measure me and it said I had a 92% SpO2.

Well, I should have been in an ambulance on the way to the hospital if that was true. And then equally their blood pressure monitor, their risk-based blood pressure monitor said my blood pressure was 165 over 125.

Likewise, I would have been an ambulance on the way to the hospital. In fact, I'd probably be the125 diastole. Gotta probably be dead to be honest.

So yeah, it's kind of scary when you, when you think that products like that because they're being sold as informative healthcare, you know, lifestyle products instead of true medical devices.

You know we really, there's a good reason for regulation.

There's a good reason why we brought, we changed the regulations in Europe because we've got to have these standards for.

Etienne Nichols: Everyone’s benefit and that makes a lot of sense. I'm not going to talk about the wearable I'm wearing now, so, but I will. So, I do want to ask you, you kind of talked about some different ways to collect data. Do you have any, you know, 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, best practices. Let's talk about wearables in general here and, and where you post.

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 that's in the same kind of 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, how you measure and how you compare devices. I'll give you an example. If you take an 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 and you do it using a teaching but simultaneously and all the rest.

Well, if you're driver developing an algorithm, you don't have to follow the ISO standard to develop the algorithm. You need the ISO standard to balance.

And scenes 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, they're not. It's not blatantly obvious when you go and look at the IDRF suggestions or, you know, 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 the iPhone was, only think of the development scope that's had and half of the regulations we work off 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 thing is, 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 in that and that's not good.

You know, trying to use your algorithm development data for a pivotal trial, you know, trying to combine them as one, that's not a very good plan. And you know, fortunately a lot of that stuff is 510k, so you're not getting that much scrutiny. But then having said fortunately, if you're not developing it the right way, it's not fortunate for a patient, so the regulation may allow you to do it. The best practice is what you should always follow. Patient safety's gotta 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're saying or. Oh, sorry, Jon, the, the feasibility data and the, you know, 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 said we were speaking about with respect to 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 represent a moment in time of what is acceptable and potentially expected. But if you have a product that is a variant or differs from the scope of some of these standards, you know, heed what Adam is saying, you know, use those as maybe some, for some guiding principles, but, but not in, in an absolute sort of way, you know, in a vacuum.

And I think, you know, the other thing that, that a lot of folks listening may be thinking is, well, I need the regulators to tell me what I need to do.

And my…

If you feel that way because you have a device that, 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, you know, if you ask the question open endedly, you may not like the answer, you may be told, oh yeah, you need to do you know, 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. You know, we have this opportunity in the United States through, you know, like 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. Fortunately, 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 you've got to do it, it's very, very hard to turn around on that.

And you know, one of the big changes with the regulations in Europe, which is kind of aligned to that, is prior to the MDR, the notified body could be your consultant.

So, they consult you, tell you what you needed to do, and you kind of 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 did 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. It 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, well, we should probably go a little further, build quality in ourselves.

I didn't want to, you know, we kind of cut you off a little bit. Adam, did you have. We talked a little bit about the software. Did you have best practices kind of in general or.

Or did we cover that? I mean, you know, are we good or.

Adam Steadman: So, yeah, I focus very much on the, on software as a medical device there. But best practices in general, I think number one best practice that companies should not forget about is make sure you follow ISO 1415-52020.

That's critical. That is the GCP standard for medical devices. And then if you're a diagnostic manufacturer, it's ISO2916 2019 and do not use the GCP for drug ich GCP, unless you're using combination product, 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. You know, a few years back, ISO 14155, 2011 was quite different from ICH GCP, but that covers so many things that are so essential when you're doing clinical trials and that really does need to be followed. So, I think that's, that's a, that's an inviolable requirement, if you like.

But having said that, you must know how many times people don't, you know, prime example, you need consent to do any kind of medical trial on people. The number of times we see small companies have just started, they got a new product and 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 finance and so forth.

And you know, it's easy to be tempted to not follow those standards, but you need to.

And then the other thing is just make sure you meet all of the regulatory, don't slip past and do your clinical trial and hope to get away with not having the insurance 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.

You know, unfortunately, particularly in the software world, it's your organization knows you're developing software, you've got to have a trail going right back today one showing how you got to where you have today.

You know, all these basic quality requirements you've got. You get an FDA BIMO audit, the biomedical monitoring audit, which you have to have. If you have a PMA submission, they're going to look at file, so they're going to look at your design files and so forth and make sure that you've done what you had 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 just not worth taking shortcuts.

Jon Speer: Yeah, that I just felt a little triggered and I'll explain that why. But before I explain that, Adam, can you. I know these are second nature, back of the hand, you know, easy for you to remember, but you rattled those ISO standard numbers off really quickly.

Can you maybe mention those again? And at the end it's probably good if we can mention those in the notes that go in the show note or that accompany the show.

Adam Steadman: So, the good clinical practice for.

I'll read it from the COVID because I had 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. There's ISO 14155 and that came out.

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 this 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 are on this quest for first in human studies or first in human use of their product.

And you know, the particular issue that comes to mind, there was a company they were basically pursuing first in Human Studies, you know, somewhere where there's. 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, 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 was 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 I just. There’re so many holes in that approach to your point. You know, if you want to do that, great. Just don't take it as a shortcut. Make sure that you're following, you know, 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.

The human use of their product.

Adam Steadman: Yeah.

So, there's two sides to that, I think. On, on one side of it, I've seen companies going to South America and so forth and, 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, we're not going to be associated with it. That's the absolute worst reason to do in another country as far as I'm concerned. And to be honest, companies that do that and, and really 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 Colombia, you could go to Peru, you can go to Argentina or Brazil.

And 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 are 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 of 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 pre-existing supply chains of devices that are competing with yours so that you are adding benefits to the local community because you're providing something that can't get there already.

And you're not competing against somebody whose 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 to go on with his organization.

So, you know, there's different ways to look at these things. And unfortunately, there's this, as I said at the beginning, there can be bad reasons for going to these countries, but on the other hand is really good, practical, sensible reasons for doing it.

Just 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 is kind of a.

It's been evolving pretty much throughout my entire career. But sometimes it seems as though a regulatory body in. In one geography is not all that accepting of clinical data that 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 respects, yes. In some respects, no.

I think there is a.

I mean, it used to be. It used to be considered that the FDA would only accept U.S. data.

Well, the FDA's 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, is it 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 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 the FDA, said no.

Why? Well, the average weight of a Korean may be 120 pounds and of Americans 220 pounds. There's a lot more pressure on that system.

And can the hotel 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 kind of changed, though now is we used to have a situation where it made sense to go to Europe and do your studies first and then 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 CE mark, but it doesn't work the other way around.

What's kind of 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, if five years ago or so we were planning to do, 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, as where they have 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, what's being 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 the downside of the MDR that I haven't heard anyone talking about.

Jon Speer: That's very interesting. I mean, because it, I hadn't thought about it from that lens, but you know, there's a lot of research institutions that, that's what they do. They're cutting edge, they're, they're, 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, 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 the patients.

Jon Speer: So yeah, and then not to mention all specialists, where are they going to practice, you know, if their facility is, is not on the cutting edge with, you know, particular technology in a particular area of expertise of theirs.

I mean, where there's going to be a migration of folks, right? You know, 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.

Adam Steadman: But.

Jon Speer: 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. 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 have been the end?

Jon Speer: Yeah, I mean, 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, not to say trivialize or minimalize 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, in clinical research and studies being happening in Europe, then it's probably not Covid in 2022, so.

Adam Steadman: Exactly. Exactly.

Etienne Nichols: I don't have any follow up questions. Jon.

Adam, did you want to, did you have anything you wanted to close out with or how we can find you?

Any last pieces of advice?

Adam Steadman: No, you got me thinking.

No, I think just to sort of recap on a couple of the main points.

Don't forget your data, get the importance of your data.

Number of times I've seen investor decks with claims made 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 in depth 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 shoestring their operations along to get to the next series of funding or whatever it is.

If you can go and ask for $10 million 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 spike your face and so my advice to people is think very carefully about what you're going 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're 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 compliance is required. Particularly if you're going PMA route. Because if you're going PMA route, you've got a BIMO audit coming.

If you've got a BIMO 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 kind of piggyback on what Adam's sharing. I mean, I, I think, you know, if you've been a listener to the Global Medical Device Podcast for any period of time, you've, you've pro.

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, you know, 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.

You're defining as well.

And 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, you know, certainly, you know, 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 smarttrial.com, if I recall. Right.

Adam Steadman: That is great news.

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 been listening, we'll include a few of these things in our show notes. So the standards 1415-520-916 hopefully got them right. But the show notes will be correct with links, so you'll have those also.

Yeah, like Jon mentioned, if you're interested more in hearing about SmartDash trial or Smart Trial, it's the Smart Dash 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.

Etienne Nichols: Bye. Thanks for tuning in to the Global Medical Device Podcast. If you found value in today's conversation, please take a moment to rate, review and subscribe on your favorite podcast platform.

If you've got thoughts or questions, we'd love to hear from you. Email us at podcast@greenlight.guru.

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