In this episode of the Global Medical Device Podcast, host Etienne Nichols welcomes back Dr. Mike Drues to discuss the critical aspects of obtaining Institutional Review Board (IRB) approval and interacting with the FDA for medical device clinical trials. They explore the roles of IRBs, the difference between significant and non-significant risk devices, and share invaluable advice on mitigating risks associated with clinical trials. Whether you're a newcomer or a seasoned professional in the MedTech industry, this episode offers essential insights to ensure your clinical studies are compliant and efficient.

Key Timestamps:

• 00:01:20 – Introduction to Dr. Mike Drues and his accolades.
• 00:05:30 – Explanation of IRBs and their role in clinical trials.
• 00:15:10 – Differences between traditional and commercial IRBs.
• 00:22:40 – Discussion on significant vs. non-significant risk devices.
• 00:32:00 – Importance of pre-submission meetings with the FDA.
• 00:44:15 – Steps to take when an IRB disapproves your clinical trial.
• 01:00:30 – Practical tips for choosing the right IRB for your study.

Quotes:

• "Most 510 devices do not need clinical data. But if you do, even for a non-significant risk device, vetting that with the FDA in advance is wise." – Dr. Mike Drues
• "You don't want to create a problem where none exists, but avoiding FDA consultation can lead to costly surprises later." – Dr. Mike Drues
• "The primary mission of an IRB is to ensure the safety of the patients at that institution." – Dr. Mike Drues

Takeaways:

Key Insights:

1. Understanding IRBs: IRBs are local entities responsible for the ethical oversight of clinical trials, ensuring patient safety and compliance.
2. Risk Classification: The classification of your device as significant or non-significant risk dictates whether FDA approval is needed for your clinical trial.
3. Strategic Pre-Submission: Engaging in a pre-submission meeting with the FDA can prevent costly delays and ensure your clinical trial meets all necessary endpoints.

Practical Tips:

1. IRB Shopping: If faced with an IRB denial, consider alternative institutions or commercial IRBs to avoid delays.
2. Comprehensive Submissions: Prepare thorough submissions for IRBs, including device descriptions, clinical trial protocols, and informed consent forms.
3. Physician Champions: Having a physician advocate at the institution can streamline the approval process and facilitate patient enrollment.

Future Questions:

1. How will the evolving landscape of MedTech regulations impact the approval process for new devices?
2. What role will real-world evidence play in future clinical trials for medical devices?
3. How can smaller companies navigate the complexities of FDA and IRB requirements effectively?

References:

• Etienne Nichols on LinkedIn
• Mike Drues on LinkedIn
• Greenlight Guru can help with Clinical Investigations
• Good Clinical Practices (GCP) regulations for IRBs

MedTech 101:

What is an IRB?

An Institutional Review Board (IRB) is a committee established to review and approve research involving human subjects. The primary purpose of an IRB is to ensure the ethical and safe treatment of participants in clinical trials.

What is an IDE?

An Investigational Device Exemption (IDE) allows a medical device to be used in a clinical study to collect safety and effectiveness data. An IDE must be approved by the FDA for significant risk devices before a clinical study can begin.

Questions for the Audience:

• Poll: Have you ever faced challenges with IRB approvals for your medical device clinical trials? Share your experiences at podcast@greenlight.guru

Feedback:

We'd love your feedback on this episode! Please leave us a review on iTunes and share your suggestions for future topics. Email us at podcast@greenlight.guru

Sponsors:

Greenlight Guru

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Mike Drues: Most 510 devices, in fact, do not need clinical data. But if you are going to need clinical data, even if it's a non significant risk device, as we talked about before, I think you're wise to vet that with the FDA in a pre sub in advance first, even though you're not required to. Some companies take the attitude, well, we don't want to create a problem where none exists. And so they'll say, well, we're not going to, we're not going to tell FDA about that. Well, I say, okay, fine, that's your decision. You don't have to. But here's the risk that you're taking. If you're going to do a clinical trial for your NSR device and you don't tell FDA about it first, and again, you have no obligation to, and you spring it on them for the first time at the point of the submission, then be prepared for them coming back and say, well, what about this other endpoint? You didn't measure this endpoint. We would like to see that. So now you may have to do a whole clinical trial over again in order to collect that information. Kaching, kaching, Kaching. You know, it's, it's, it's a, it's a calculated risk. Some companies might choose to take that risk other companies might not.

Etienne Nichols: Welcome to the global medical Device podcast, where today's brightest minds in the medical device industry go to get their most useful and actionable insider knowledge direct from some of the world's leading medical device experts and companies.

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Etienne Nichols: So I don't always know how or why these things happen, but it's, it's fantastic. And I love to be among the stars. Absolutely.

Mike Drues: Absolutely, absolutely.

Etienne Nichols: Thank you for bringing that up. Thank you for mentioning that. And again, thank you for being on the podcast IRB Institutional Review board. First of all, maybe we should talk about what is an IRB? Maybe we should start there.

Mike Drues: Yeah. Great question, Eddie. And as always, thank you for the opportunity to have this important discussion with you and your audience today. This is one of the many common questions that I get from my customers as they develop medical devices, especially if clinical data is going to be involved in a clinical trial. For example, they'll ask me, do we need FDA's approval to begin the clinical trial? Do we need IRB's approval to begin a clinical trial? And because this is such a commonly asked question, I thought it would be a good topic of conversation for one of our podcasts. So the short answer to your question of what is an institutional review board or IRB? Simply put, it's the way I like to think of it, Erin. It's a backup. It's a sanity check to the FDA. In other words, mechanistically, an IRB is typically made up of a handful of people, typically about five or six members, both a mix of scientific and medical folks, as well as you have to have at least one non medical folk. Unlike the IRB, sorry, unlike the FDA, that has responsibility across the entire country, the IRB is local. It has responsibility only to that particular hospital or medical school or institution or whatever it is that they're representing. And as a general rule, we'll talk more about this in a moment, but as a general rule, if you're going to do a clinical trial for a new medical device, you have to have the IRBS permission. Some people call it approval, but it's technically, it's really not an approval and the FDA sense of the word, but you have to have their permission. And then sometimes, not always, but sometimes you need to have the FDA's permission to begin the clinical trial as well. We'll come back to that in just a moment, but here's a not so hypothetical question for you. Let's say that you're going to do a clinical trial at, say, three different sites across the country. For the sake of names. How about if we say Harvard and Hopkins and Stanford? All right, so you want to do a clinical trial of your new medical device at these three institutions. How many groups, how many approvals, or how many, you know, oks would you need to get to begin that trial?

Etienne Nichols: Well, based on what you just said, it sounds like you need at least three. One from each one of those institutions.

Mike Drues: Correct. You need to have one of each of those three institutions. So in this case, Harvard, Hopkins, Stanford, you need each one. And by the way, the decisions of the IRB are independent of the FDA. They're also independent of one another. So it's possible, for example, for the. And I'm only using those names because most people have heard of them. But it's possible that Hopkins and Stanford IRbs say, yeah, no problem, go ahead and begin the clinical trial. But Harvard, for whatever reason, may not be comfortable with that. So it is possible, it doesn't happen often, but it is possible that you might get disagreement between the IRBs. That's not necessarily a bad thing. In fact, that's part of the medical safe check and balance system, if you will. And the decisions are also independent of the FDA as well. So it's possible for the IRB to say yes and the FDA to say no, or vice versa. So there's a lot of different possibilities, and I have a few scenarios I can share as we continue, about what to do in these different situations. But does that at least answer the question of what is an IRB?

Etienne Nichols: It does. I am curious, just. Just kind of an offshoot of what you just said. What about the standardization across irbs? Not so much that you get a yes. If Stanford says yes, Harvard will say yes. That's not what I'm talking about. But just a standardized approach, knowing that there may be differences in the interpretation of that standardization. Are there any things like that?

Mike Drues: Yes. The shorter answer is absolutely. That is, we've talked about before, Eddie, and is endemic across all regulation, not just irbs. Technically speaking, IRBs are supposed to be following the GCPs, the good clinical practices. But just like any regulation, that regulation can be interpreted in many, many different ways. So why don't we just to put a. So that we don't have to talk in generalities and platitudes, let's take a specific example. This is an example that I was involved with a few years ago. We had a product. Technically, this was a combination product because it involves stem cell. But it doesn't matter. A couple of the IRBs said yes, no problem. One IRB said no. So in that kind of a scenario, Adian, what do you think the company's choices are to do if one IRB says no, what are. What are their options?

Etienne Nichols: Well, I mean, if there's three, I guess you could proceed with the two. And I'm just thinking of different options. 1 may be well, I'll just take this to another institution and see if I can get another institution to okay it. Or I could alter my test.

Mike Drues: Yeah, that's, you know, coming from somebody who's sort of a self proclaimed novice about this, I think you know more about it than you're giving yourself credit to. Those are the two options that the company has. You can try to work with the IRB to try to address whatever concerns they have, or at the end of the process, if that particular IRB, for whatever reason, is being difficult, then you can do what we call IRB shopping. In other words, you can shop around. You can say, okay, Harvard, as much as we would like to work with you, you know what? Quite frankly, you're just being too difficult, and it's not worth it. We're going to go down the road to, you know, to Yale or to Cornell or to NYU or something like that. So this is something called IRB shopping. And by the way, by the way, the same thing happens sort of in the, in the regulatory world. It's what I call notified body shopping. You know, in the EU, for example, you're required to work with a notified body, but it doesn't say, nor should it say which one you need to work with. So if you're working with one and for whatever reasons, you're not getting the. The satisfaction that you think you should be getting, there's nothing from preventing you to shopping to a different notified body. So the regulatory logic, the precedent here is the same, but going back to my scenario that I described a moment ago, it turned out that the one institution that was, quite frankly, being obstinate about this, and remember, the key variable here is that the device involves stem cells. One of the requirements of IRBs is that you have to have a non technical member of that. Of that IRB. In other words, not a physician or an engineer or a scientist or something. It has to be a non technical person. Of course, different institutions interpret what non technical means in different ways, but in this particular case, one of the people was a member of the clergy. Well, long story short, there ain't nothing that we're going to say to get this person to agree with a stem cell clinical trial. So the first attempt is to try to work with the IRB, if at all possible, just like work with the FDA, if at all possible, to try to resolve whatever differences that you have to come up with, what the attorneys like to call a meeting of the minds. If in spite of your best attempts, you can't do that, then the other option, as you just pointed out, Edien, is to shop around for somebody else, a different institution. You know, this is what we call IRB shopping. And just to peel back the onion on that a tiny bit further, Adien, there's two types of irbs. There's what I call a traditional IRB, and that's the one that people are most familiar with. That's the one that exists at that particular institution. So, you know, Hopkins will have their own IRB, Stanford will have their own IRB, Harvard will have their own IRB. And by the way, in the case of these very, very large institutions, they usually have multiple irbs. They might have one IRB for cardiovascular products, another IRB for urology products, a third for gastrointestinal, and so on. So that depends on the organization. Those are all the traditional irbs. But then the other option that some institutions will recognize is what we call a commercial IRB. A commercial IRB is basically a Irb for hire, if you will. In other words, instead of using the IRB that happens to come along with, you know, Harvard or Hopkins or whoever it is, you can use a commercial IRB. And again, Eddie, and the precedent, the regulatory precedent for this is the third party review for a 510, where for certain kinds of medical devices, you don't have to have the FDA review your 510, you can hire a separate company. It's what we call a third party reviewer to ostensibly act as a. As a surrogate, if you will, for the FDA. The same principle applies here with a commercial IRB, that the commercial IRB has to be allowed by that particular institution, it has to be recognized by that institution. So it may very well be that once institution will allow you to use a commercial IRB if you want to, whereas another institution will not. That's totally up to them. But in most cases, because you're paying the IRB just like you're paying a notified body, you have a certain expectation of, you know, timely responses to your inquiries and so on and so on. So, like everything regulatory, and there's advantages and disadvantages to both. The purpose of our discussion today is to try to point out what the different options are and some of those advantages and disadvantages. Does that make sense?

Etienne Nichols: Yeah, it makes sense. And I love the illustration with the three p five third party 510K. That makes a lot of sense. One quick question on the advantages. If you have that commercial IRB route, can you potentially cast a wider net with institutions, assuming Stanford, Harvard, and Hopkins? Just use your examples. All except perhaps that commercial IRB is that the case?

Mike Drues: Exactly correct. Once again, kudos to you, because I think you know more about this than you give yourself credit to. One of the suggestions that I make to my customers is if you're going to do a clinical trial in multiple sites, multiple locations, and most of the time, FDA typically likes to see multiple sites. Oftentimes the magic number is three, at least three different clinical sites. But take that number with a big grain of salt anyway. If you can identify one commercial IRB that is recognized by all three of those sites, then you can kill, in this case, three birds. With 1 st, you get the blessings of that commercial IRB, and then that will be transferable to all those different sites. So that is a. If it's possible, it's not always possible to do that, but if it's possible in your particular case, that could be a very significant savings in terms of time and probably money as well.

Etienne Nichols: And I know there's several other questions I want to get to. I want to ask one more follow up question about that. And so, just to kind of use the example with FDA and taking, pursuing my submission, there's the pre sub process. When it comes to IRB, does it make sense to talk to them prior to just submitting your protocol, or there, is there some kind of process similar?

Mike Drues: Yeah. Great question. You're doing what my attorney friends like to say, leading the witness. So thank you for leading me. Terrific question. So here's the thing. A moment ago, I said that almost anytime you're doing a clinical trial, certainly a clinical trial for a new medical device, when it comes to label expansions, that's a little bit different. But if it's a new medical device getting onto the market for the first time, and you need clinical data, you will undoubtedly need permission of the IRB or multiple irbs, depending on the number of institutions. Now the question becomes is, do you need permission of the FDA to begin a clinical trial? Do you want to take a guess at that one, Erin, since you're. Since you seem to be on a.

Etienne Nichols: Roll there, my guess is yes, the guess.

Mike Drues: It's a good guess, but not quite. Let me give you a hint. What is the shortest, most accurate, and most succinct answer to every question in regulatory affairs? There's no exceptions, including this one.

Etienne Nichols: Well, it depends.

Mike Drues: It depends.

Etienne Nichols: I want to throw a caveat. So this is. I actually tried to find something, but I couldn't quite figure out exactly where I was pulling this information from. So maybe you can just tell me, hey, you're off. Or maybe you're right. You know, you tell me. For a while there, historically, my understanding was IRBs were accepting maybe too much, because maybe had a university hospital that benefited from some of these clinical trials and clinical investigations, and the FDA doing things that maybe the FDA wouldn't necessarily approve of. So a lot of IRBs are now looking at that and say, we'd like you to have that approved by the FDA first. So there's a little bit of a political backlash. I don't know if that's something that I'm just making up or if I.

Mike Drues: No, I don't think you're making it up. I would. I would spin it in just a slightly different way. Look, there's no question there's a potential conflict of interest here. Absolutely no question whatsoever. Because any institution, even the most reputable medical schools in the United States, they are making money off of doing clinical trials. It's what we call the non direct fees, and those can be very, very substantial. So for somebody to say that there's no financial incentive for an institution to want to do a clinical trial, I think it's a bit naive, to put it politely. But I wouldn't go so far as to say that, of course there are exceptions, but as a general rule, most IRBs remember their primary mission. They're really their only mission in life, is to ensure the safety of the patients at that particular institution. I would like to think that no IRB would allow the potential for their institution to make money to come over to trump a possible safety risk when it comes to biocompatibility or electrical safety or something like that. But, of course, as we both know, Eddie, and there are occasionally some, you know, some bad actors in this industry, and that's why we have regulation, and that's why we have the FDA. But coming back to the original question, whether or not we need FDA permission to begin a clinical trial has to do with the risk of the device. And I've done podcasts with Greenlight before about the different systems for risk. Just as a recap, for example, we have here in the United States three different independent, but also interdependent systems that we handle risk with. One is the classification system. Class one, class two, class three. That system is what most people are familiar with. There's a second classification, second risk based, well, for the lack of a better term classification system, it's what we call a significant risk versus a non significant risk device. And that's the one that's applicable here. But the third system for risk is the medical device software classification system. These are three different independent but also interdependent ways that we handle risk here in the United States. And while on one hand, as you and your audience probably know Ed in, I'm a subject matter expert for FDA in several different areas, one of them being risky. So this is a topic that I do know a fair amount about. On one hand, risk is a very complicated topic, much more complicated than a lot of people think. But on the other hand, maybe we go out of our way to make it even more complicated than it needs to be because we've got these three different systems for risk. Anyway, that's enough of the tangent. We can put a link to that particular podcast, SR versus NSR devices in the podcast notes if people are interested, the reason why it's applicable here is because if your device is a significant risk device or an SR device, then you are required to get an IDE or an investigational device exemption prior to beginning your clinical trial. If your device, on the other hand, is a non significant risk device or NSR device, you're what we call IDE exemption. And in that case, there's no obligation for you to go to FDA to begin your clinical trial first. You still have to go to the IRBs. You always have to go to the irBs, but not to the FDA. But even though that's the regulatory requirement, Ed, in my advice to companies, and I do a lot of NSR devices, obviously, but even for companies that have an NSR device, and by the way, the determination of whether or not your device is significant risk or non significant risk, that is up to the company. That is not up to the FDA, that is not up to the IRB, that is not up to anybody else. That's up to the company. Is that putting the Fox in charge of the henhouse? Absolutely. No question about it. But that's exactly what the regulation says. So even in the case where you have a non significant risk device, I almost always recommend taking it to the FDA first, usually in the form of a pre sub. Want to guess as to why I recommend doing that, even though it's not required? Why would a company take an NSR device to the FDA, usually as part of a pre sub, when it's not required?

Etienne Nichols: Well, personally, I would not want them to up class that to a significant risk and then potentially invalidate whatever clinical investigation I'm performing.

Mike Drues: Very good. So that's one of the two reasons why I make that recommendation. In other words, sort of a sanity check. Say, okay, mister, and misses FDA reviewers here's our device. This is what it does, this is how it works, and so on, for all of the following reasons. It is a non significant risk device. And then FDA will say, great, you know, that sounds logical to us. Or they'll say, hold on a second here. We don't quite see it that way. And that's when the poker game begins. So, reason number one that I recommend bringing NSR devices to the FDA. I don't bring it just as a standalone NSR question, but I usually embed it in an existing presub is to make sure that FDA sees it also as a non significant risk device. Because if they don't see it as a non significant risk and you submit your 510 or de novo or whatever it is later on, now you're in a whole bunch of problems and you haven't even started talking about your device yet. That problem doesn't happen an awful lot, but it does happen from time to time. The second reason why I make the recommendation to take an NSR device to the FDA, even when it's not required, is to avoid a very common problem. Where a company does a clinical trial, they get approval of all the IRBs and everything else. They submit their 510 or the de novo or whatever it is. FDA says, this looks great, but we want this additional information. And now maybe they want some additional clinical endpoints or something like that, or a higher power of the trial or something like that. So now the company has to go back and in some cases, to do a clinical trial all over again to collect that addition of information. You don't need an MD or a PhD or an RAC after your name to appreciate kaching, kaching, kaching. It's a very easy problem to mitigate, if not totally avoid, by taking it to the FDA first. But one last thing, and I'll be happy to let you chime in with questions, because you're asking some great questions. Remember my regulatory mantra when it comes to communicating with the FDA, and that is, oh, my gosh.

Etienne Nichols: Hell, don't ask.

Mike Drues: Thank you. Hell, don't ask. Lead, don't follow. So please don't go into the FDA and say, do I need to do a clinical trial? Because, I mean, what do you think they're going to say? Of course you need to do? 10 million people or something like that. You say, we're not doing a clinical trial, and here are the reasons why. Or we are doing a clinical trial. This is what it's going to look like. This is the design. This is the inclusion and exclusion criteria. These are the endpoints, the power, the number of sites, and so on and so on. And FDA will come back and say, yeah, that sounds great. We look forward to seeing your results in a few months. Or they'll say, hold on a second here, we don't quite see it that way. And that's when the poker game begins. So, very long winded response to your question, Etienne, if you even remember what your original question was. But, but good question.

Etienne Nichols: So kind of, you answered the question. That was fantastic. I appreciate that. Do you know when do we need FDA permission for a clinical trial? Maybe on the flip side, what about IRB approval? When do I need IRB approval to begin a clinical investigation for my device?

Mike Drues: Great question. So the easy part of the answer is, and I alluded to this earlier, if you're working on a brand spanking new device, a device that is not on the market here in the United States, it might be on the market in other places in the world, but not here in the United States, and you need to do a clinical trial. Absolutely. You're going to need IRB approval, as we talked about earlier, and you're going to need IRB approval at each and every one of those institutions that you're going to be doing your clinical trial at. Whether or not you need FDA approval to do the clinical trial, that's going to be contingent on whether it's significant risk or non significant risk. As we just talked about a moment ago. That's the easy part. That's the black and white part, the harder part, and this is where we get into the gray areas. And my favorite areas to play in are the gray areas, because it's not, you know, yes or no, it's not binary. There's, there's matter of interpretation is, let's say, Eddie, and for the sake of discussion, you have a device on the market already for one particular indication. You, through your post market surveillance, you start to learn of people using this device for another indication. Technically, that would be considered off label use. But you and your companies decide, you know what, that's a pretty good use of our device as well. For whatever reasons, it wasn't part of our original 510K or our original de novo or original PMA, but we think it would be a good idea to add that because then we can advertise for that particular, what used to be an off label use. And so let's do a clinical trial to collect the data. We could do real world evidence as well, but let's just focus on the RCT the randomized clinical trial, would we need a IRB approval for a device that's already on the market to do a clinical trial for an indication that is not currently on the FDA cleared or approved label? That's clearly in the gray area. The regulation does not say one way or the other. In that particular case, I revert to institutional policy. Remember you asked earlier, Etienne, about the regulation that the IRBs follow? They all follow the GCPs, but like all regulation, they can be interpreted in different ways. I know I won't name specific institutions, but off the top of my head, I can give you a laundry list of institutions that as a matter of institutional policy for their institution. If you want to do a label expansion, and this is true for drugs as well as medical devices, if you want to do a label expansion, if you want to add a new indication, they will still require an IRB approval. On the other hand, there are some, probably not a lot, but there are some institutions that are a little more liberal, if you will, and they basically say, well, once the product is approved by the FDA for something, people can use it for whatever they want. And so if you want to do a clinical trial, you know, on this other thing, then, you know, go ahead and do it. You don't need our particular permission. My advice to companies, though, is to find out once you've identified which institutions you're going to do your clinical trials at. And that's a topic of a different discussion. But once you identify those, find out what their policy is for label expansions and doing a clinical trial of off label use. But still, I think that it's probably, even though it might not be against the regulation not to get the IRB approval for an off label clinical trial, I still think it's the right thing to do. It might not violate the letter of the law, but it would certainly violate the spirit of the law. And one other thing that I would just point out before we start to wrap this up, Edion is in those situations where your device is a non significant risk device and you are what we call IDE exempt, and you do not have to go to the FDA prior to your clinical trial, I think it's a good idea to, but you're not required to. In that event, keep in mind that the only thing. How do I want to say this? The only thing standing behind the, standing between the patient and the safety of your device is the IRB. There is no FDA in this particular case, keep in mind, and I personally think this is a weakness into gcps and the good clinical practices, IRBs, because they exist at institutions like hospitals and medical schools and so on, they're for the most part, clinical people and scientific people, not necessarily engineering people. So when it comes to issues like biocompatibility or electrical safety, these are things that are kind of assumed by most clinical people. But an engineer, a good biomedical engineer, I'm sure, I hope, would never make such an assumption. Right. And so because you're not dealing with the FDA in this case, you're only dealing with the IRB. The review of the IRB is critical to the safety of the patient. We're not even talking about the efficacy, the device. We're talking about, you know, basic safety. Like you, you plug something into the wall and you don't get electrocute. You know, I mean, that's, you know, that's basic engineering. But you would like to think that that doesn't happen, but sometimes it does. So when you're only dealing with the IRB, I think there should be a greater burden on the company to really make sure that it's safe because there is no FDA oversight in that particular case. Does that make sense?

Etienne Nichols: It does make sense. And you alluded to it at the beginning, too, when you talked about risk management and how risk is one of the primary. You know, I was, I was actually just looking at, before our conversation, 45 CFR part 46, which talks about requirements for institutional review boards, and I noticed that risk is mentioned 51 times. And so it's just really interesting. So I imagine someone listening to this might have the question, what information do I need to provide for the IRB for review? How long does the whole process take? You mentioned the difference between commercial and traditional. Maybe that timeline being different, but what about those? What can people expect?

Mike Drues: So, great question. In terms of timeline, unfortunately, I can't give you or I don't know of any national IRB statistics. If somebody does know, please share them with me. But I imagine they're going to vary all over the place, because irbs vary all over a place. But here's one of the questions that I always recommend to my customers to ask. When they're shopping around for individual institutions to do a clinical trial, ask them about the mechanics of their IRB. For example, who makes up their IRB? How often do they meet? Some IRBs will meet once a month. Some will meet once a quarter. Some will meet more frequently or less frequently than that. So if, for example, you're dealing with an IRB that only meets once every, every quarter, that's once every 90 days. If you, just, dumb luck, happen to submit your paperwork the day after their last meeting, you're going to be waiting for three months before they even look at it. So those are legitimate questions to ask. And then finally ask them for their particular institution. What is the average response time for coming up with a decision as to, yeah, this is approved to begin your clinical trial, or no, it's not. And ideally that would be the icing on the cake. The flour on the icing on the cake would be, especially if you're dealing with a large institution that, you know, has multiple irbs for different clinical specialties. If you're dealing with a cardiology product, for example, try to get statistics or information specific to cardiology. You're not probably interested so much in urology or ob gyn or some, you know, you're interested in cardiology, or if you're working in neurology, asking them, you know, for, for the review statistics for the neurology irbs so that you can do that apples to apples comparison. So that's the timeline piece in terms of the content. I have a template that I give to my customers when we're preparing, you know, to submit to an IRB. To an IRB. It's very similar to a lot of the information that you're going to submit to a, to the FDA. For example, you have to have your device description, what your device does, how it works, its mechanism of action and so on. You need to have, because the IRB is interested primarily in the clinical trial, you need to have your clinical trial protocol, what you're going to do to the, to the patients, what you're going to be measuring, how much, if any, you're going to follow up and so on. And by the way, you also have to usually include all of the collateral information that's going to come up, that's going to be exposed to the patient, for example, the informed consent form that usually has to be part of your IRB package, any kind of direct to patient or direct DTP advertising information. Sometimes the IRB might request that. So all that kind of information, probably the most important piece of information for the IRB, though, especially if it's a non significant risk device, is your non significant risk device justification. In other words, here's my device. This is what it does, this is how it works. For all of the following reasons, we have designated this as a non significant risk device. And here are all the reasons why I have had it happened and actually just before the holidays, it happened very recently. Where we have a device. In my opinion, it's a very, very legitimate, non significant risk device. But the IRB is wanting some confirmation from FDA that FDA also sees this as a non significant rise device, non significant risk device. The problem is there is no official document where that FDA will give you that will say, this is an NSR device because they'll give you an ide if it's an SR device. But there is no, like a non ide, you know, if it's not. And so we had to go back to the IRB and say, look, there's no regulatory requirement for us to give you a document from the FDA. Oh, by the way, we took it to the FDA as a pre sub, and we can share with you our meeting notes where everybody seemed to agree that this is NSR. We can show you the other irbs that we're dealing with where they never asked such a question for, you know, proof that this is NSR. So again, because everybody is following the same rules, but they're not necessarily following or interpreting the rules the same way. You get different interpretations. And in that case, you can do whatever you can, Eddie, and to try to come up with a medium of the mind so that you could proceed and do your study there as planned. But at the end of the day, if they're saying that, hey, we need this piece of paper, and you can't get this piece of paper, you say, you know what, institution x, we would love to work with you, but quite frankly, you're being too difficult. We're going to go down the road and work with institution. Why that is IRB shopping.

Etienne Nichols: Right. And I know we talked about a little bit, I might ask you a little bit more, but I just think that's interesting how the SR versus NSR, there seems to be a FDA sensitivity versus specificity when it comes to determining that. Any other, any other piece of advice when it comes to choosing that IRB? I mean, obviously, if you're going to an institution, you may be locked in with that institution, if that's your goal. Any other thoughts or advice for companies shopping for an IRB?

Mike Drues: Yeah, well, I guess it depends on the company specifically. What I mean is, what's more important to you, the institution name or the IRB in some cases, especially if you're dealing with a brand spanking and new technology, let's be honest, if you're a me too 510k or even, there's a lot of me too pmas, even though they're class three, they're still pmas. We have dozens and dozens of bare metal coronary stents. They're all basically the same. Yeah, they have slightly different designs in terms of the wires, or it's a wire versus a hypotube or something like that. But at the end of the day, you know, a bare metal coronary stent is a bare metal coronary stent. So what is more important, the name recognition of having, like, a really well known medical school, you know, an Ivy League school or something like that. And by the way, I teach in an Ivy League school. It's. I'm not sure if Ivy League still means what, what it used to mean, but that's a topic for a different discussion or if it's better, if it's more important for you to work with an IRB that's going to be timely in their responses. Responses that's going to be willing to work with you, you know, to be helpful, as opposed to just being a barrier to say, no, you cannot do this. And instead, you know, they have a more positive attitude, like, well, if you. We think it would be more appropriate if you do it this way instead of that way or something like that. Exactly like working with a notified body. Exactly like working with the FDA. You want somebody that you can work as together with as a part of your team. You shouldn't view the IRB, nor should you view the FDA as an obstacle, you know, somebody to just, you know, a barrier to just get over in order to get your product onto the market. Maybe that's a little naive, maybe that only happens in the universe of unicorns and rainbows, but that's what I try to do. Am I successful all the time? No, not quite all the time. But I'm successful more often than not. As long as it's based on valid engineering and biology, the regulation, we can work that out. But the medicine and the biology and the engineering, that has to be sound, first and foremost. If not, you're a snake oil salesman. It's as simple as that.

Etienne Nichols: I keep going back, but I know this isn't a topic about risk management, but I keep thinking about, well, what are some of the mistakes, you know, in communicating companies could make in the evaluation of communication of that risk to IRB? You know, just similar to that we talk about with FDA. But do you have any thoughts? I know with the FDA, for example, maybe one of the things that's beneficial with the submission is a cover letter and actually spelling that out so that they can have that in the back of their mind as they go through your submission, is there something similar with an IRB or any other last piece of advice? What?

Mike Drues: Well, I like to put. It's a great question, Eddie, and thank you for bringing it up. I like to tell a story. Obviously, this should be nonfiction, right? But. But still a story where you have an introduction, you know, a body, a series of main points, and then a conclusion. I remember many years ago, to improve my. My presentation skills, I was in a group called Toastmasters, and they had this expression, tell them what you're going to tell them. Tell them, and then tell them what you just told them. This is a practice that I use in my written communication as well. So whether I'm putting together a pre sub for the FDA or a package, you know, for an IRB, I'm going to tell a story. I'm going to say, you know, here, start out with, here's my device. This is why I've developed it, and this is how it works, and this is what it's going to do. And this is how it kind of compares to other things out there. We're not talking about, like a 300 page PhD dissertation, but, you know, a few paragraphs is sort of a background. And then, pardon me, the purpose of this document is to provide the information necessary such that, you know, that you believe that this is safe and appropriate to use in a clinical trial at your institution. And then you go into all of the different parts that you need to go into. And at the end of the day, you reiterate, you know, we, you know, in this document, we presented the following information. One thing that I tell a lot of my customers when it comes to the FDA, but it also applies to irbs as well. We should not be so naive as to think that every FDA reviewer or every IRB member will read every page of your document cover to cover. It's just, yeah, maybe in the rainbow, in the universe of rainbows and unicorns, perhaps, but not in the real world. That just ain't going to happen. But usually most people will read the beginning, the introduction, and then the ending, the summary and the conclusion, and they might read a few parts in between. So this is the reason why sometimes, Mike, you're saying, well, you're repeating the same information. Well, a certain degree of reputation is okay. One of my frustrations with a lot of regulatory submissions, though, is they're so long, thousands or maybe tens of thousands pages long. Why? Because the same information is being repeated over and over and over. I swear, these people, some people must be getting paid by the page rather than by the hour or something. I don't know. But a certain amount of repetition is okay. Too much repetition. No, no, no. That's not what I'm advocating here. Just like they used to teach in elementary school. I'm not sure if they still do, you know, write it like a story. You have an introduction, you have a series of main points, you have a conclusion, and then hopefully that'll be enough to do the job. If it's not just like a submission to the FDA, they might come back to you with some questions and you can respond either via writing or having a meeting. It depends on the policies of that institution. I try to avoid going back and forth with a lot of reports and a lot of emails for all the obvious reasons. Once we make the original submission, if there are questions, I usually ask to have a meeting to discuss it, to make sure that everybody is on the same page, because I've seen it happen many times where a company will answer the question that they think is being asked, when in fact they're answering a totally different question. And so obviously, not only is that just a waste of time, but now you're introducing the possibility of creating new problems where no problems existed before. So for all those obvious reasons, I think looking for an IRB that's willing to work with you is good advice.

Etienne Nichols: I love that. I love the advice about storytelling that's really applicable across pretty much every. You know, I had a professor in college who would tell us about Chekhov. I couldn't even tell you who Chekhov is at the moment. He. But I can remember the phrase where he said, if you put a gun on the wall in act one, it better get fired in act two. Yeah. Don't just repeat yourself for no reason. I have a lot of takeaways today. I personally didn't know about the traditional versus commercial IRB. I really appreciate the three P 510K example. And to differentiate those two as well as the SR versus NSR, we'll put links to those in the show notes. But, yeah, this is a really good conversation. I appreciate it.

Mike Drues: Oh, I'm glad, as always, to have this opportunity to share this information with you and your audience. Regrettably, I see so many companies making, in some cases, the largest medical device companies on earth that have like hundreds and hundreds of regulatory folks on their team, you know, and they make some of the most basic, you know, the most elementary level, elementary school level mistakes. It's just, you know, so I'm happy to share the information and, you know, rather than you know, reiterating everything that we just talked about, I think the couple most important messages that people should come away with is, number one, if you're going to need clinical data for your medical device, and remember, not all devices do. Most 510 devices, in fact, do not need clinical data. But if you are going to need clinical data, even if it's a non significant risk device, as we talked about before, I think you're wise to vet that with the FDA in a pre sub in advance first, even though you're not required to. Some companies take the attitude, well, we don't want to create a problem where none exists. And so they'll say, well, we're not going to act. You know, we're not going to tell FDA about that. Well, I say, okay, fine, that's your decision. You don't have to. But here's the risk that you're taking. If you're going to do a clinical trial for your NSR device and you don't tell FDA about it first, and again, you have no obligation to, and you spring it on them the first time at the point of the submission, then be prepared for them coming back and say, well, you know, what about this end, this other endpoint? You didn't measure this endpoint. We would like to see that. So now you may have to do a whole clinical trial over again in order to collect that information. Kaching, kaching, kaching. You know, it's a calculated risk. Some companies might choose to take that risk, other companies might not. The other thing that I think that people should be aware of is when you're dealing with institutional review boards or irBs, keep in mind the word there is institution. Some of these institutions are very large, very bureaucratic, very political. I gave you the example of the stem cell product that I was involved with a few years ago. So don't underestimate the time and effort that it might take you to get this through that particular institution. And one of the things I always like to recommend to companies is if you can have a physician champion within that institution, somebody that's, you know, on staff, you know, in the, in the medical school at that particular institution, for example, who's a big fan of your device, your technology, if they can help, I don't want to say grease the wheels, but if they can help, you know, move things along, so to speak, kind of like fiber, if you will, you know, through, through the, through the balls of the institutions, that will, that will help a lot because some of the bureaucracy, it's just, it's just boggles the mind.

Etienne Nichols: That was actually the one of the things that came to mind when you were talking about label expansion and determining what institution to go to. I would think an institution that is using your device for that off label use, that seems like it. Well, depending on the liberality of the IRB, I suppose, you know, those could be two different things, but it seems like that could be at least a good starting point.

Mike Drues: Yeah. And here's an interesting statistic, more in the general clinical trial area as opposed to specifically with irbs. But the single biggest reason, the most common reasons why clinical trials either don't finish on time or in some cases don't finish at all is because of lack of patient enrollment or lack of patient recruitment. So in that label expansion example that you just alluded to Etienne.

Etienne Nichols: Yeah.

Mike Drues: It makes perfect sense to go to an institution or at least include one of your institutions, somebody that has, that is already using a lot of your devices so that maybe patient enrollment is not as big of a challenge.

Etienne Nichols: Yeah, yeah, great point.

Mike Drues: If you work with an institution that's never used and is not familiar with your device, then recruitment obviously can be a little more of a challenge.

Etienne Nichols: Well, this is really good. Thank you so much, Mike. I appreciate you being on the podcast. Those you've been listening. You've been listening to the global medical device podcast. We thank you for being here and definitely check the show notes. We're going to have a lot of links and resources and obviously feel free to reach out to Mike as well. We'll put his, his email in the link as well. He mentioned that template, irbage, so that could be a good resource to potentially reach out about. Thanks again for being on the show, Mike. We'll let you get back to it.

Etienne Nichols: Thank you so much for listening. If you enjoyed this episode, can I ask a special favor from you? Can you leave us a review on iTunes? I know most of us have never.

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Etienne Nichols: Just look for that.

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Etienne Nichols: Thanks again for listening and we'll see you next time.