Kulkarni Law Firm -Clinical Research’s Post

Transcript

In this episode, we discussed the latest trends in clinical research, focusing on the evolving landscape of IRB oversight in 2024, including the roles of HRP, So that's a HARP and OHRP and the need for greater federal agency oversight. Here's what we're going to cover. IRB changes in 2024. What is an HRP? What is a HARP? What is ORI? What is the need for federal agency involvement? What is the impact of the new guidance and the Trump administration? What is the role of OHRP and AARP? Can the FDA actually regulate an IRB? Our guest is Eddie Edens. Let's get into it. Why IRB's may be impacted, if at all, in 2024? What are the big things that have happened that impact them? Like you said, we've had some really big things happen even in this final stretch of 24. And you and I have been making a lot of comments and talking a lot about it behind the scenes and publicly is, of course, the recent FDA guidance being finalized on decentralized elements in clinical trials. And what does that mean? Being able to utilize, you know, HCP's different modalities? What does that mean for the patient? What does that mean for clinical care providers who are in research? What does that mean for the quote UN quote, traditional research site or center that's not used to maybe using as many decentralized elements? What does it mean for the sponsors writing the trials and the protocols and how they're going to set that up logistically, how they're going to create that flexibility? What does it mean for the data, right, If you're collecting data different ways, if different patients are having different experiences on the trial, does that change the validity? Does that change the control? Are we on to something and maybe we just aren't circulating in the right circles And there's two pieces to that and one is IRB's and two is oncology. And what I mean by those two things is what does this change if anything for how and what an IRB would approve. I mean the FDA guidance doesn't come right out and tell an IRB, you know this is approval criteria, it's not. And the Arabs have navigated for, you know, many years now using different elements of decentralization in trials, right? Whether you want to call them hybrid DCT, whatever you want to call it. Most the HRP's that I know have done this pretty darn well given the the need, the quickness, the turnaround and the lack of regulation and guidance. So now that it's official. Now what? What is an HRP? Why would people care? We most people have heard of an IRB. You talked about policy, so could you explain those terms? P stands for Human Research Protection Program. And what a lot of folks don't realize is an IRB is actually a component of an HRP. So human research Protection program, the easiest example I can give you is think of a large traditional Medical Center that has, you know, medical school, large hospital attached very, you know, traditional in the United States where we seek and find care. And in that particular environment you have an HRP that's going to go across all these different. Research compliance areas and mechanisms, because it's not just the IRB, there's all sorts of regulations around doing research with animals. There's all sorts of which is outside the HRP, but connected, sorry. There's all sorts of potential for conflicts of interest regulation needs. There's all sorts of potential for quality auditing needs, whether that is, you know, being able to actually have auditors who go out into your clinical trial community or maybe even audit the HRP itself, right? And be able to be prepared. You also might have research integrity and misconduct as a part of your HRP. So there's multiple different slivers and elements and arms to a human research protection program. So your HRP is going to be subject to the FDA. If you're doing FDA regulated research, you're going to be subject to the Office for Human Research Protections. What is a HARP and how does that fit into this and how does ORF fit into this? So a HARP is, and now you'll know why it's an acronym is the Association for Accreditation. Of human research protection programs, which is why we need an acronym. And it's it's an accredited accrediting body for human research protection programs. And it is your gold standard. If you go on to, you know, an academic medical centers IRB website or human research protection HP website and it has a gold seal that says a Harper credited that is truly for that particular space. The it's not required, but considered the gold standard. For having your HRPP, you know, inspected, audited, accredited and adhering to the highest standards of conduct above and beyond just what's required by the regulations. And so if you are a Harper credited, you will then have extra standards and extra policies and extra requirements to keep that accreditation up as a part of your HP. And you're, you're doing that, you know, to be the highest standard HRP you can be, but it's a ton of work. I mean, you are subject you're basically. Willfully subjecting yourself to yet another, you know, auditor, yet another regulatory body so you talk about. Ohh, harp, you talk about a harp. How does ORI fit into this? First of all, so ORI is the Office of Research Integrity. So they're over falsification, fabrication and plagiarism, which is what is truly known as research misconduct. We say in IRB land or HRP land or auditing world, you know, non compliance. And we kind of use the word misconduct, but the true federal definition is FFP fabrication falsification. Naturism and there's more to it than that. I don't mean to simplify the regulations. It's, it's very, you know, intricate work. But the Office for Research Integrity is then that federal arm under DHS that overseas any federally funded research and any allegations of misconduct. So if you're accepting federal monies, then your HRP is going to have to have research integrity. You should have it anyway. A single organization like DOGE wants to do using Elon Musk using. RFK Junior, is this what we're looking at in the future where we're saying there's O harp, a HARP, RIFD all overseeing clinical research? Do we need all these organizations, especially when they're all looking at just clinical research? I mean, I have my own thoughts on Doge just from having worked in the political environment. If they were to take flight and be able to be productive, that's exactly some of the redundancy you look at, right? So Doji. Coming in from the redundancy and efficiency perspective and saying, OK, I mean, yes, this is research with humans. And we do, you know, we've really screwed it up in the past and it has all sorts of potential safety and risk issues. We take it very seriously. But my gosh, I mean, do we really need it? Like you said, you know, HARP, OHRP, like all the acronyms, I mean, could we not make this a more efficient process? Would that not save the patient more money in the end, right? Save, get from the bench to the bedside faster in certain situations. And I could see depending on how the nominations play out. Certain appointees in those particular spaces going well, we already don't trust the process either as they are. And we appreciate that you want to reduce the redundancy, but we don't think that's the answer because we're we actually are suspect even with the redundancy that we're doing enough, right. And so then you're going to have a political. Uh, nightmare on your hands from a different perspective. And, and I think where the industry would sit in that is at least for most of us and most of the folks you and I, you know, tend to have dialogue with and work with is we would say, please eliminate some of the redundancy. We are all for, you know, risk based quality management. But at the same time, there is such a thing as overkill and red tape. I mean, there is a reason that for example, an in-house HRPP IRB is always going to have. Their turn around times than a large commercial IRB because they're they're just instanced in more politics and bureaucracy and it slows them down. Given the Trump administration and Elon Musk's perspective and Vivek Ramaswamy's perspective on improving and adding efficiencies to the federal government and enhancing innovation, what is your perspective on this guidance tying it into real world evidence? Would this all translates into with the Trump administration? 1st, when you're talking about efficiency and decentralized elements and trials, I think there's been, and we saw this a lot in 2020 with the issue of decentralized trials getting tied into automatically being related to diversity or automatically related to, you know, reaching more patients or automatically was deemed patient centric. That's not always necessarily the case at all. And so I, I don't want us to get into once again saying, oh, we used centralized elements and so that. Increases efficiency or decreases efficiency because I don't think you can blanket statement that there's certain trials that it's just not going to make sense to do decentralized elements for there's certain, you know, maybe we even within a trial, there might be certain visits that aren't the right fit in that particular trial. There might be, you know, when you're talking about a phase one oncology study where you have a hospital stay, you know, you start to get into some nasty logistics in terms of being able to make that decentralized continue. Shout out to Dan Fox. So actually calls this out. It does talk about actual individual meetings, maybe decentralized, but not the study itself. You know, when you think of Musk and dosage and what they're going to be charged to do in terms of efficiency, I definitely could understand why they would want to look at our industry. And they want to look at these layers and layers and layers of regulatory and see if there's not, you know, a lack of efficiency. They want to look at the logistics and OPS. But I also think that this is still a. It's not a new enough concept in the sense that we haven't put it in practice. We have, but it is now officially regulated. We have opened the door toward HCP's involvement and use in a new way. Even those of us within the industry are still arguing about what that looks like and what you can do with that and what you can't and where you can use it and where you can't, right. So we can't even decide there's not enough track record to say it's efficient or it's not for for a Dodge like organization or agency to then come in and go, OK, we need to clean this up. We need to fix this. What should? Old harp and a harp do in this scenario, did they pass their own guidances in the in this area? Do they reconcile? Is this like FTC FDA type of memorandum where they have to go? So the first one is it doesn't change anything. And here's what I mean by that, Eddie. We've already been approving these studies with different types of decentralized elements like you said. And astute point, they've been around since the 20 tens. They got popular fodder in 2020 because everybody realized what was going on in the benefit they might provide in that setting. And so we actually, this isn't really new information. We've already been making these risk based assessments and deciding what they could use. We've been doing it for years. We appreciate that. The FDA brings new perspective and has opened the door. But admittedly, you know, we don't regulate the 1572 anyway, right? So like what do we care who's listed on it? What does that matter? How does that change our approval criterion anyway? It just doesn't, it doesn't impact it. And so this is great. We expect to see more submissions that have HCP, you know, utilization in them and we'll work through those logistically with each submission as we should. But there's really nothing to change here. And I could see that being a valid point, right, because they've already done the heavy lifting, they've already made the risk based assessments as the years have ticked by. I could also see there being. A different conversation in that we've worked so hard in HRP world to create a sense of harmonization between the FDA and the IRB. Folks do not understand that regulatory setup. No one expects you to. It's very complicated. You pointed out that the FDA technically does not regulate the Irbs, yet we see warning letters and we see 480 threes for for Irbs. How does that work? FDA can actually audit an IRB. Let's say you're an organization. That does FDA regulated research, but you also do non FDA regulated research, right. So you're large organization and you make a determination about a study that comes through your HRPP, specifically the IRB that it is not something that is subject to FDA regulation, right. Maybe someone wants to repurpose, reuse a test article wants to look at something like that's already available over-the-counter etcetera. And where there's a really good example of this that we see most commonly is. Someone wants to use something that is approved and on the market. I always use the vitamin C sepsis example that has proven in some type of an off label setting to be very viable for use, but has never been studied and approved. And in that moment you have to decide as an IRB whether you're going to say, look, I need the FDA to sign off on. They don't believe you need the appropriate regulatory submission like an Ind to move forward or they do. And so let's say you're IB decides we think you're not subject to the FDA. And then a year later, two years later, and you know, while the trial is being conducted, you have an audit, maybe it's a routine audit by the FDA when you're carrying a large portfolio. They're going to come look at you with the IRB when they find that the FDA can in fact actually issue a 483 to the IRB, to the HRP and say you did this incorrectly, or we're concerned about your policies or procedures, or we found deficiencies in how you process your submissions. Or maybe it's this very specific example, you know you got it wrong, you got the analysis wrong and this should have been FDA regulated or it shouldn't have been any which way IRB's are subject to. So it's a very interesting relationship when you look at the regulations, essentially the FDA has the right to inspect and view. They have the right to come in and issue based on the trial and the fact that you are conducting FDA regulated research. But again, the IRB. The regulations around how you approve research and how you do your operations and what the expectations are for your performance are not established by the FDA.