What’s the difference between an LDT and an IVD and what does that have to do with the Theranos case? In this episode, we dig deep into this topic.
Mike Drues, a frequent returning guest to the Global Medical Device podcast is the president of Vascular Sciences. He has a Ph.D. in biomedical engineering and extensive experience with Regulatory Strategy, the FDA, and the history behind most of the regulations.
In today’s episode, Mike Drues and I spoke about the topic of Lab Developed Tests (LDTs), the ongoing Theranos case, and the state of LDTs & IVDs.
Listen to the episode to learn more about Lab Developed Tests and what some examples of them are, what testing and regulations are required for LDTs, and how Theranos was able to market a test without the typical testing rigor.
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Some of the highlights of this episode include:
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Why Lab Developed Tests fit in with medical devices
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What the difference is in LDTs and IVDs
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How LDTs are regulated
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Examples of LDTs
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Why labs develop their own tests
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The risk when it comes to LDTs
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Why non-invasive LDTs can be listed as class 3
Links:
Memorable quotes from Mike Drues:
“A lot of people like to talk about what FDA regulates. I like to talk about what FDA doesn’t regulate.”
“Remember, regulation is about the interpretation of words.”
“There is no difference in terms of the technology between an IVD and an LVT. The difference primarily is who uses it and where it’s developed.”
“If the hospital does one thing, they’re treated one way; if a company does exactly the same thing, they’re treated another way. Something’s not quite kosher about that logic.”
Transcript:
Etienne Nichols: Hey everyone. Welcome back to the Global Medical Device Podcast. My name is Etienne Nichols. I'm the host of today's podcast and with me is Mike Dreus, a common name on the Global Medical Device Podcast.
Glad to have you with us today, Mike. How are you doing?
Mike Drues: I'm well, thank you, Etienne, and nice to speak to you and your audience and Happy New Year. This is the first podcast that we're doing in 2023, so happy new Year to you and everybody listening.
Etienne Nichols: Absolutely. Yeah, it's, it's flying by for me, but I know we're only two weeks in. We'll see how the rest of the month goes.
Today's episode, we wanted to talk about the LDTs or the lab developed tests, kind of like an ongoing saga and whether or not the Theranos loophole should be closed.
Maybe before we get into too many details though, maybe we should talk about, you know, we're the Global Medical Device Podcast. Why would we be talking about laboratory developed tests?
You want to answer that?
Mike Drues: Yeah. Great question. And by the way, thanks as always for the opportunity to have this discussion with you and your and your audience.
Simply put, as we'll discuss in more detail, a laboratory developed test or an LDT is a type of in vitro diagnostic or IVD. And IVDs are regulated by the FDA, specifically by CDRH, the Centers for Devices and Radiological Health, as a regulated medical device.
So, in terms of your question of how does it fit into this particular podcast series, I don't think there's any doubt, or maybe there is, that this is a topic that is of legitimate discussion for a regulatory. Sorry. For a medical device audience.
Etienne Nichols: Well, yeah, it's interesting because when I just look up, I don't know, laboratory developed tests, one of the headliners right now is the Theranos case. And you know, I already mentioned, should we close that loophole?
And I don't know, one of the things when I think about the Theranos case, if you're not familiar with it, there was a, a test developed and it was fraudulently claimed to do so many different things, but it fell under the laboratory developed test rather than the in vitro diagnostic.
Mike Drues: Or did it? That's one of the questions that I'm hoping to dig into.
Etienne Nichols: But anyway, great question. And I want to, I want to, I want to know what your, what your thoughts are on that too. But my other question is, so when we talk about there being a loophole and maybe we'll get to this in a little bit here, the this seems like a worst-case scenario and I wonder is maybe you can give some, some context or history.
Is that what's driving some of this conversation or has this been a conversation for a while?
Mike Drues: I think the short answer to that question, Hedon, is both.
This has been a conversation for quite a while, even before the Theranos fiasco as I like to call it. This has been going on now for probably a couple of decades, this debate about lab developed tests and whether or not they should be regulated by the FDA.
But certainly, as we'll talk about in more detail later, Theranos was one of the things, probably the single event that really brought this whole subject, if you will, to the attention not just of the medical device community, but of the political community and also to the American public. But we can get to the details of Theranosis. We continue our discussion.
Etienne Nichols: Sure. Maybe, maybe what we ought to start with is what is a laboratory developed test? And one of the things that I'm curious about because you already mentioned a little bit about what one is, it falls under the heading of an in vitro diagnostic.
But what's the difference? When does, when does it start falling under even more so on IBD?
Mike Drues: Yeah, great question. So, I think it really, in order to truly understand this before delving into lab developed tests in particular, let's just take a half a step back, Etienne, and talk about in vitro diagnostics or. Yeah, IVDs.
So, what's an in vitro diagnostic? Well, simply put, and I'm paraphrasing from the code of federal regulations, a in vitro diagnostic is a reagent or an instrument or a system that's intended for diagnosis of disease or condition, including a determination of the state of health. And I love phrases like that. Determination of state of health. Why? Because I have no idea what that means.
But simply put, an IVD, as I said, is some sort of an instrument or system.
Usually, it uses a sample from the body of biological fluid or tissue. Could be saliva, could be blood, could be urine, could be lots of different things in order to perform some sort of measurement, maybe making a diagnosis or something like that.
So, because it's intended to mitigate, treat or prevent a disease, injury or condition, it clearly fits the CFR definition of a medical device.
Because as someone in the audience may remember, I did one of my many webinars for Greenlight a year or two ago on what is a regulated medical device. And I went through in some detail the CFR definition of a medical device, which is many, many paragraphs long.
However, the essence of that definition, if you were to boil it down into its simplest form,
is something, anything other than a drug that's intended to prevent, diagnose or treat a disease, injury or condition. And it's that last part, Etienne, that's the most important.
Prevent, diagnose, or treat a disease, injury or condition.
Nobody can dispute the fact that an in vitro diagnostic fits that definition. So medical. So sorry. So IVDs are medical devices as defined by the CFR. As a result, they're subject to FDA regulation.
And I don't want to overgeneralize when it comes to regulation.
We're talking about the regulatory side, that is the pre-market side, showing that the test is safe and effective, but we're also talking about the manufacturing quality side, making sure that the test is reliable and reproducible, and so on and so on.
So maybe to illustrate further, Edin, would it help to share some quick examples of in vitro diagnostics?
Etienne Nichols: Yeah, okay. Yeah, I'd love to hear that.
Mike Drues: Okay. Or I know you are very knowledgeable in this area as well. Do you have any thoughts on what you think is an IVD in terms of an example?
Etienne Nichols: Well, I was thinking more on the other side. What could potentially be a lab, lab developed test, but as far as that, in a second. Yeah, but when I think about in vitro diagnostic, well, Covid tests, for example, I don't have a lot of examples coming to mind just at the moment. But yeah, if you have any in front of you, I'd love to.
Mike Drues: Yeah, I don't mean to put you on the spot, but I do like to sometimes put you on the spot. So just sort of fair warning. So, yeah, COVID test is a perfect example of an IVD,
pregnancy test, HIV tests, blood glucose test, urine test, even cancer tests. These are all examples of in vitro diagnostics. IVDs can be used either in a hospital or a doctor's office,
sometimes in the back of an ambulance or even in a person's home, like a COVID test.
The point is that all of these things are regulated by the FDA. And remember, because they're regulated by the FDA, they're regulated in those two ways. One is on the premarket side in terms of safety and efficacy, but the other is on the manufacturing or quality side in terms of reproducibility and so on.
And both of those things are going to be in important.
When we now talk about lab developed tests, because.
Etienne Nichols: Yeah, go ahead.
Well, when you talk about those things, I mean, I'm almost, my mind goes back to the beginning when you were saying, when we were talking a little bit about Theranos.
And I said, well, that was, that wasn't an IVD. And you said or is it.
And everything that you gave a lot of the things that were claimed previously by maybe Theranos or other companies who may be an LDT, they, you know, to do it very similar to what you're saying, whether it's the glucose, the, the blood testing, HIV and so forth.
So, what is your opinion on, in that, in that situation then?
Mike Drues: Well, before I give you my opinion, let's, let's talk about what an LDT is and how does it differentiate from an IVD? So, we just spend a couple of minutes talking about an IVD.
What is an LDT? An LDT is a, is a subset of IVDs.
That, and the biggest difference, certainly from a regulatory perspective, is that LDTs are not regulated by the FDA, at least not right now.
My question to you, Etienne, and before I continue on, is why do you think LDTs historically, and this goes back a couple of decades now, but why do you think historically LDTs have not been regulated by the FDA?
Etienne Nichols: Well, my understanding is right now they're regulated under CLIA, the Clinical Laboratory, trying to remember the, what is that acronym? Clinical Laboratory Improvement Amendment Certification.
So, and I believe that that happened in 1988.
So, they were a laboratory that developed a test.
And the idea is similar to how a physician is able to use a device under that certification. The, the test that was developed didn't need to be submitted to the FDA because of that reason.
It was in a location that was, you know, specific and a single device that was probably simpler than maybe a manufacturer might be putting together.
Mike Drues: I think you're going in the right direction, Arian. Let me give you a hint and then I'll ask you the same question again.
So, the philosophical intent, if you will, of an LDT is something that's developed in one particular laboratory or clinic or hospital for use only in that laboratory or clinic or hospital.
So, this is the key difference between an LDT and an IVT. It's something that's intended to be used in a. Sorry, it's intended, it's developed in a single place, a single lab, a hospital or clinic, or something intended to be used only in that place and not sent to other places or sold to other places or so on.
So, with that big hint, there's actually a very simple regulatory explanation as to why FDA does not regulate, at least in the past, up until now anyway, LDTs.
Etienne Nichols: Well, I would assume it would be because the risk is much lower.
Mike Drues: Good guess, but no. And incidentally, I love it when people guess, and they guess wrong.
Etienne Nichols: Yeah.
Mike Drues: In fact, as we'll talk about, in some cases, the risk can be just as high or even higher. The simple. I'll give you one more hint.
Etienne Nichols: Okay.
Mike Drues: And you know, a lot of people like to talk about what FDA regulates. What I like to talk about is what FDA does not regulate. And that's the, that is the answer to the question I'm asking you right now.
What does the FDA not regulate?
Etienne Nichols: Consumer or. No, that's not.
Mike Drues: Well, I didn't mean to other product.
Etienne Nichols: Categories, things that are regulated in other ways.
Mike Drues: So, here's the short answer.
Etienne Nichols: I got to get it.
Mike Drues: No, no, no, that's okay. As my attorney friends like to say, let me lead the witness. FDA does not regulate the practice of medicine.
And this is a very, very important point. FDA doesn't regulate the practice of medicine. That is, FDA cannot tell physicians what to do. The only thing they can do is tell us, many industry what to do.
And so, when a hospital develops a test in their own lab for use in their own lab,
one could easily argue, and this is the argument that has been made for decades, that that is the practice of medicine.
Just like pharmaceutical compounding, just like reprocessing of reusable medical devices, just like in many cases, 3D printing, these are all technologies that FDA has not regulated in the past. Why? Because it's the practice of medicine.
I'm not saying I agree or I disagree. I'm just simply providing the justification, the rationale for why LDTs have not been historically regulated. Because when you look at the examples of LDTs, they're exactly the same examples as the ones that I just mentioned for IVDs.
In other words, oftentimes the technology is exactly the same, the labeling is exactly the same. It's just a matter of who develops the test, whether it's a company or a lab, and where is that test used. And by the way, Etienne, and although this debate has been going on now for years, decades, I find it interesting that nobody seems to have pointed out that we call these things laboratory developed tests, or we do not call them company developed tests.
I guarantee decades ago, in the very early days of LDTs, if these were developed by companies, not individual laboratories, without a doubt they would have always been regulated by the FDA for all the reasons that we've already discussed, not the least of which is it clearly fits the CFR definition of a medical device.
So, these are laboratory developed tests, not company developed tests. Does that help?
Etienne Nichols: That does make sense.
So, when, when you talk about it that way, it makes it, it makes sense.
When I think about what the difference is in an LDT and an IVD, it does make, it does help in that regard, for sure. The thing that maybe it, it muddies the water a little bit more in this specific case.
If I think of Theranos, because that is a company, but, but it's also a single company's laboratory. Is that, is that how that worked?
Mike Drues: Kind of depends on how you define laboratory. It also depends on how you define hospital. You know, when the Theranos case happened several years ago, I was one of several people that were invited to, to come into FDA to chime in on this.
And one of the questions that I raised, somewhat rhetorically, but also very seriously, is how do you define a, a single laboratory?
You know, the example that I use was the Mayo Clinic. The Mayo Clinic is a very large hospital. They have multiple buildings.
So, if they develop a LDT in one building of their hospital, are they allowed to use it in the building across the street that's also part of their hospital?
The Mayo Clinic also has facilities in different states, not just in Minnesota, but in Arizona, and I think in Florida and maybe some other places as well.
So, if the Mayo Clinic develops an LDT in, say, in Minnesota, are they allowed to use it in a mail facility in Arizona or in Florida or somewhere else? You know, this illustrates one of the many recurring themes that we've talked about a lot in the podcast over the years, and that is regulation is about two things.
One, it's about the interpretation of words, and second, it's our ability to defend our interpretation.
We can interpret the words in many different ways. What does a single lab mean? Does it mean, you know, just one hospital? As long as it has the same name, it doesn't matter how many facilities they have or where they're located.
Or do we interpret it in a different way? Clearly, Theranos had a, let's just say a fairly aggressive or maybe even loose interpretation of the concept of an LDT.
Etienne Nichols: So, when you talk about the definition of a hospital or what is what constitutes a laboratory, my mind thinks, okay, well, they are regulated by CLIA or regulated by CLIA, governed by CMS.
However, you look at that, surely there's a definition out there.
I don't know what it is at the moment. I don't know if you're familiar with that. I mean, has that not been defined.
Mike Drues: Even by CLIA definition? Of what a laboratory?
Not a specific definition. And even if there is, you know, I work with a lot of companies. They, they, they pay me to interpret words in lots of different ways.
So quite frankly, and this might sound a little brash to some of, in our audience, but I'm going to be hon, I don't care. You give me any definition that you want, I will interpret it in the way that, you know will be, will make sense for the company. Or alternatively, if I'm working on the side of the FDA, I will interpret that same definition, you know, on behalf of the FDA.
So, remember, regulation is about the interpretation of words. But more importantly, Edian, you're exactly right. I don't want to give our audience the impression that LDTs are not regulated at all because that would clearly be factually incorrect.
They are regulated to a certain extent. They are regulated under the CLIA regulation. And CLIA, among other things, is interested in things like accuracy and precision and sensitivity and specificity.
But these are all things that if you took a traditional IVD to the FDA, they would be interested in exactly the same thing.
So, one of the things that bothers me about this whole debate and the reason why and when we didn't talk about the, the, the political influences here, but the reason why we're talking about this at the beginning of 2023, the new year is because just last month in December when Congress was debating the, the, the, the budget for FDA for The fiscal year 2023, one of the things that was personally what was, was specifically not passed was the Valid Act.
And the Valid act is verifying accurate leading edge IVCT development.
Basically, this would have given FDA the statutory authority to regulate LDTs like all other IVDs, even though it had bipartisan support and even though there was debate, although maybe not enough debate, and even though even Advamed the industry association advocated for passing valid, it did not go through.
And so, the reason why I bring that up is because that would, that could have cleared up a lot of this mess.
But right now, they are regulated by CLIA. But let's put it this way, CLIA regulation is not as robust as FDA regulation. I'm trying to be kind and also to be simple here.
And then the other thing that I am coming back to my original point, Etienne, in the biggest opposition to the VALID act came from people representing these hospitals and these clinics, they argued that this would be too burdensome if they were to require getting a 510(k) or De Novo or a PMA on all of these LDTs.
Well, philosophically speaking, the regulatory burden, in other words, what's necessary to show that the, the device, the test is safe and effective and reliable and reproducible and so on. It's exactly the same whether it's regulated by the FDA or not.
In fact, here's a rhetorical question, Etienne, and, and feel free to, to, to agree or, or to, to disagree, but the safety and efficacy and the, and the, the, the reproducibility and the reliability, all for in vitro diagnostic or for an LDT?
Do you think that that's going to matter if it's being developed by a company or by a hospital?
Etienne Nichols: Really? It shouldn't? Absolutely not.
Mike Drues: Yeah, absolutely not. I mean, safety and efficacy of any medical device is determined by you know, hundreds and hundreds of different things. But one thing that I will guarantee that it's not determined by is who develops it or, you know, whether it's used in a single facility or multiple facilities.
Absolutely. Regrettably, in many ways, I think the whole focus of this discussion in this debate has been on the wrong, the wrong part of the problem.
Etienne Nichols: And that's true. And when I think about the political side and the reason, I asked you earlier about the Theranos case is that what is driving this? The question in my mind when I just doing a little bit of research about all this is if this has been a sufficient means for regulating LDTs, and then we have a worst-case situation that happens driving a regulation, could it, could it be too burdensome?
That is kind of one of the questions in my mind. Well, but at the same time, if this is a loophole that a company can use to mass produce a test, then it makes total sense. Then if the regulation is good enough, something should change.
Either the LD should be regulated or if that's good enough, an IBD should be allowed to be regulated in the same way that an LDT is. That, that is just the opinion I have.
And I suppose you have, you, you add color as to which way it should go. But yeah, I do lean towards more of the, the regulation of the IBD.
Mike Drues: Well, I, I, I like, you know how you characterize the LDT as a loophole. I would remind you that many people to this day characterize the 510(k) also as a loophole on the law.
But we won't go on that engine, at least not right now.
Yeah, it's I'm sorry, I forget if there was a, if there was a question there somewhere.
Etienne Nichols: No, no, not a question per se. I suppose if I were to.
To ask a question, if, if we rewind the clock before Theranos, we already asked the question why, why would labs develop their own?
Or did we ask the question why? Why do we develop. Why would a lab develop their own?
Mike Drues: Yeah, I don't think we actually asked that. So, so let's go back because I really want to dig into LDTs. We talked about what they are. Let's talk about some examples and let's also talk about why they're developed by laboratories.
So, you remember the examples I gave you of IVDs a few minutes ago?
Recall those examples because they're going to sound very familiar to what I tell you. Now for LDTs, examples of LDTs include things like chemistry tests for detecting glucose in the blood or some other kind of a protein in the blood that's tested on some kind of a body fluid.
A fluid, sorry, a flu test, a drug test using mass spectroscopy, for example. These are all exactly the same, or at least very, very similar, substantially equivalent, if you will, to FDA regulated in vitro diagnostics.
So, it's really that who develops it and where it's intended to be used is the key differentiator. As a biomedical engineer, and as you know, and many of our audience know,
my background is in biomedical engineering and that's what my PhD is in. There is no difference in terms of the technology between an IVD and LDT. The difference primarily is who uses it and where it's developed, and so on and so on.
In terms of why labs develop these tests, this is another thing that I think it's important for our audience to understand. There's basically two most common scenarios of why a lab or a hospital would develop their own test.
The most common scenario is it's a new test. In other words, they develop or use a new LDT because there's an equivalent commercial test is not currently available.
This happens a lot in the detection of rarer genetic diseases like Huntington's disease and so on. These are diseases that only affect a very, very small number of people.
And so, it's probably not worth it for a traditional for profit medical device company to develop a test to do this. There's just not enough money in it for them.
So, the hospital tries to fill that unfit, unmet need by developing the test themselves. You know, what do they say? Necessity is the mother of invention.
Etienne Nichols: That's right.
Mike Drues: The other reason why labs often develop these tests is if they want to take an existing IVD and modify it in some way to do something else, to do something a little different.
And interestingly enough, in that particular scenario, Etienne, when a hospital modifies an existing IVD, let's say you have an IVD on a market from a medical device company, it has a 510(k).
Now the hospital, for whatever reasons, they want to make a modification to that IVD. Now, actually, technically, FDA considers that IVD no longer to be an IVD and now it becomes an LDT.
Any guess as to why?
Give you a big hint? It's the same answer before the practice of medicine. Bingo. So good. So you're learning the practice of medicine, just like in pharmaceutical compounding. For example, if your doctor says, take 10 milligrams of this particular drug and a 10-milligram pill is not available, but you have a 20-milligram pill and you cut it in half, you're modifying that pill. And therefore, that's the practice of medicine FDA has not nothing to do with.
But how about this not so hypothetical scenario?
How about a hospital chooses to take a IVD that has a 510(k), they make a modification to it, the manufacturer of the original IVD finds out about it, and let's just say they have some concerns as to whether this modification is kosher or not.
Does that company now have a obligation to go to the hospital and say, hey, we have been made aware that you're using our test. Thank you for using it. But, oh, by the way, you've modified the test, and we're not sure if that test is now still safe and effective. I hope Etienne and you don't have to have a JD after your name from Harvard Law or Hopkins or somewhere else to appreciate, you know, ka ching, ka ching, ka ching.
There could be some very interesting product liability ramifications here.
And as our audience knows, I spend some of my time, you know, acting as an expert witness in medical device product liability cases. So, I'm giving you, you know, a hypothetical but maybe not so hypothetical scenario.
Etienne Nichols: So, from an obligation, when you use that word, obligation, from a regulatory standpoint, they might not be obligated, but what you're saying is from a business standpoint, they should be concerned potential, or.
Mike Drues: Or maybe I'm naive, but let's just say from an ethical perspective.
Etienne Nichols: Well, I was going to bring that up too, but.
Right, absolutely.
The other thing, I thought you were going to go a different direction with that because I started thinking about ad promo and the Companies who might be thinking, oh, we have an additional indication for use, for example, rather than, you know, resubmit or look at this again, just suggest, start suggesting to other companies. Obviously, that is a litigation waiting to happen, but that could be a temptation.
Mike Drues: Interesting idea. And I'm sure that there are companies that would probably like that option. If I was, you know, consulting for one of those companies, I would say, I would quote Elmer Fudd in, in the Bugs Bunny cartoon. And that is be very, very careful because you've, as you alluded to a moment ago, you could be going down a potentially tortuous and dangerous path. I think it probably could be navigated safely and effectively,
but you really need to do it very, very carefully.
Etienne Nichols: Yeah.
So almost three things you need to think about. We talked about the regulatory business, but absolutely the ethical. I would a hundred percent agree with that.
The risk is interesting when it comes to LDTs.
And I don't know if we have time to go into that or if we should have a second episode with your thoughts as far as how that applies.
Mike Drues: Well, since you opened the door, let's start and then we'll see how it goes. Part of the justification in the past for LDTs not being regulated by the FDA. And again, I'm not saying I agree or I disagree. I'm just simply trying to present all of the different arguments, kind of to steal the metaphor from Fox News to present a fair and balanced approach.
So, we talked earlier about the primary justification why LDTs are not regulated because they're the practice of medicine.
Another justification is that many of these have in the past have been low risk kinds of products.
And that is a gross simplification, to say the least for a whole bunch.
As you know, I happen to be a subject matter expert for FDA in several different areas, one of them being risk.
I see even outside of the LDT realm, I see a lot of people making the assumption that if a product is non-invasive and IVDs and LDTs are by definition non-invasive, if a product is non-invasive, it's by definition low risk.
And that's absolutely not the case. At least not necessarily.
Many non-invasive devices are in fact low risk, but some of them are not. Can you think of an example of a type of device that never comes in contact with the patient and yet is a very, very high risk?
Even a Class III device like an MRI machine?
Etienne Nichols: Possibly.
Mike Drues: Good guess, but no, those are actually Class III devices.
There are several examples, but some of them are in vitro diagnostics. For example, a IVD that's intended to diagnose cancer, that IVD is not coming in contact with the patient.
In some cases, it's not even being used in the same room or even in the same building as the patient.
And yet an IVD for cancer, almost without exception, these are almost always regulated as Class III PMA devices.
And there's a particular form of risk, a particular type of risk that makes it a Class III as opposed to a Class II or lower. Can you guess what that is?
Etienne Nichols: I was thinking of a question, so can you say that one more time?
Mike Drues: Yeah. Why? When it comes to. I said a moment ago that IVDs for cancer are typically regulated by the FDA as Class III PMA devices.
Etienne Nichols: Right.
Mike Drues: But they never come in contact with the patient. They're never, they're not. They're probably not even used in the same room or as I said, sometimes in the same building as the patient.
So, most people, when they think of risk, they think, well, gee, how can something that's, that's never comes in contact with you, never touches you. How can that be a high-risk Class III device?
Etienne Nichols: Well, it influences everything that comes after it.
It could potentially influence your care if you're, if you're. I don't know, I'm just thinking of, like, what type of cancer it is. Let's suppose it's breast cancer. That could result in a mastectomy or something like that.
That would be potentially devastating depending on what the results are of that, of that test.
Mike Drues: Yeah, you're definitely going in the right direction at the end. So, kudos to you for being willing to get up to the plate and let me help you along just, just a little bit.
So, if you know, and our audience may remember that one of my most popular webinars that I did for Greenlight a few years ago is my three-bucket approach to risk, which has now become an adopted risk standard for the FDA, although they refuse to give me credit for it. But that's a topic of a different discussion.
Just to recap. Bucket number one is what I call the probability of direct harm.
And this is the most obvious form of risk that most people think of. This is the only form of risk that's addressed in the design controls.
That risk for an IVT or an LDT is zero because it doesn't come in contact with you.
Bucket number two is the probability of harm of not using the device. And this is a PMA requirement. It's not a 510(k) or de novo requirement. In other words, what alternatives are there available alternative devices, alternative drugs, alternative surgical procedures, relating that risk to LDTs. I said one of the reason why hospitals develop an LDT in the first place is because probably there's not another test out there that's commercially available.
So, the probability of harm of not using is significant because there's not an alternative.
But it's really bucket number three. That explains the question, why are these non-invasive IVDs, Class III PMAs. It's the probability of harm of providing the wrong information.
In other words, false positives and false negatives, telling the patient that they have cancer, when in fact they do not. That would be a false positive or the worst-case scenario.
And this is exactly the reason why It's a Class III PMA device, is telling the patient they do not have cancer, when in fact they really do.
And that is the single reason why these kinds of tests, whether it's an LD, sorry, whether it's an IVD or possibly even an LDT, can in fact be very high-risk devices, in spite of the fact that they never come in contact with the patient.
These are all. This is the beginning of the discussion of risk when it comes to LDT, but there's some other aspects of it as well. If we want to do this in our next discussion, maybe this is a good time to do that.
Etienne Nichols: Yeah, that's, that's, I think that's great. We can do that. I was just going to add one on because when I was looking at the Theranos case, that, that actually is one of the things that's going on with the class action lawsuit on behalf of Arizona patients.
There was a false negative for, and one of the people who experienced that actually had a heart attack with a heart attack within a month of getting his results, according to the complaint. So, it's not a hypothetical, to use your words. Absolutely.
One of the other things that I was just gonna circle back and reemphasize on the risk associated with LDTs is the example you used of a hospital using an IVD and altering it, and now it's an LDT, whatever the risk was for that IBD, now it's an LDT. If we assume LDTs are low risk, or that's part of the definition, then that kind of backfires a little bit when you think about going upstream.
Mike Drues: Actually, that's a very good point, Etienne, and thank you for reminding me of that. That's something that I should have mentioned just to remind everybody.
So, if a hospital modifies an IVD under a 510(k), it now becomes an LDT.
But think about it this way.
If the company who has the device on the market, if they want to modify it, they will either have to notify the FDA of that modification in the form of a special 510(k) or a pre sub supplement, or if they choose not to notify the FDA, they can do that.
But they're still supposed to do what we call a letter to file. This is all under the general umbrella of change management, something that I've, you know, spend a lot of time talking about in these, in these podcasts and these webinars. But here's the irony.
If the, if the hospital makes a modification to the device, which used to be an IVD as a 510(k), do they need to notify anybody? Absolutely not. They don't even have to notify the FDA that they're doing an LDT. Why? Because it's the practice of medicine.
I think at the very least that's ironic, maybe even hypocritical, to have that sort of a differentiation. If the hospital does one thing, they're treated one way. If a company does exactly the same thing, they're treated a different way.
Something not quite kosher about that, that, that logic.
Etienne Nichols: Well, we'll plan to have another episode to dive into a few other questions as far as what we can do about this and some best practices, perhaps tips for people, for people who find themselves in the middle when the earthquake parts, finally, when this valid act finally is passed.
So, we'll see.
Mike Drues: And by the way, I think just very, very quickly, when will the valid act pass? I think the answer is very, very simple.
If and when another Theranos tragedy occurs, unfortunately, that's when this is going to happen, because regrettably, and this is not unique to this situation, most of the time,
regulation is created retrospectively, not or reactively, not proactively. In other words, something really bad happens.
Now let's create some regulation to prevent it. I think it's very unfortunate that there has been such a delay, not just, you know, in this last congressional budget that was passed, but for years and years.
And imagine, you know, the explanations. These people who are making these decisions are going to have to try to, you know, spin on the television when something. I hope it doesn't happen, but the laws of probability say that sooner or later it probably will.
I'm working with companies right now in the LVD space who are very, very tempted to put their products onto the market as LDTs.
And I'm really trying to hold them back. And they keep saying to me Mike, we can put it on. It's like a wellness device. We can put it on, put it on the market.
You know, today we don't need anything from. From FDA or whatever. That's a hard argument to push back on.
So, if and when there's another the Theranos like situation. And in our next discussion, I want to be able to dig into how Theranos specifically is related to the LDT situation, because I think there's some interesting twists and turns in that part of the puzzle as well.
Does it take another tragedy, you know, to. To get people to. To wake up? Sometimes it does.
Etienne Nichols: One person told me that sometimes regulations can be boring, but the things that led to that regulation are usually very interesting.
Mike Drues: So that'd be well said. I don't think that was me. I wish I could take credit, but I don't think I can.
Etienne Nichols: I'll look it up so I can make sure I do give credit. But we'll. We'll include links to some of these resources and to these acts so that you can read a little bit more about them.
And I'm looking forward to the next conversation. Mike, thank you so much for taking the time out and having this conversation with us today.
Mike Drues: You're welcome. Thank you.
Etienne Nichols: All right, we'll see you all next time. 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.
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