Revisiting the FDA’s Proposed Single IRB Mandate: Navigating Changes and Aligning for Success

Transcript

Craig Rotzler: 

Hello, everyone, and thank you all for joining us today. I’m Craig Rotzler, the lead event producer for WCG, and we have a great panel lined up for you today. And here with us, we have David Forster, our chief compliance officer, joined by Sandy Smith, senior vice president clinical solutions and strategic partnerships, and we also have, Donna Snyder, executive physician, all with WCG. Today, they’re going to be talking about, revisiting the FDA’s proposed single IRB mandate and navigating changes and aligning for success. 

So now we’re gonna hear from our panel first, and we’ll be answering some of your questions at the end. If you have any questions, please feel free to use the Q&A icon located on the bottom of your screen, and you can type your questions and click send. 

Now I’d like to introduce and turn it over to our first speaker, David Forster. It’s all yours. 

David Forster: 

Great. Thank you, Craig. Hello, everyone. My name is David Forster, chief compliance officer for WCG, and I’ve been with the company since. So, background in law and medical ethics. 

So what we wanna talk about today are two FDA proposed notices of proposed rulemaking. The first of these is on cooperative research or otherwise known as the single IRB requirement. And the second is on the protection of human subjects institutional review boards, which has several elements, but we are going to concentrate on consent. So moving to the cooperative research. The cooperative research is titled that way because that is the actual heading on the regulation. But, really, what we’re thinking what most people refer to it as a single IRB requirement. 

And so let’s get into that. 

I also wanna start by noting that these NPRMs, notice of proposed rule makings from FDA, are intended to harmonize the FDA regulations with the common rule to the extent possible. 

So you might ask yourself what is the common rule? Well, it is the informed consent and IRB regulations that have been adopted by sixteen different agencies. The most prominent of those in research funding is Health and Human Services, which includes NIH, but there are other agencies, you know, including Department of Defense, Veterans Administration, NASA, etcetera. So a lot of federal agencies that conduct and fund research. 

The 2018 changes to the Common Rule were intended to largely improve the consent process and reduce regulatory burden, you know, predominantly on minimal risk research, but, you know, overall is fine. 

Forward button. There we go. Okay. So, let’s look at the purpose and the legal basis for this. The purpose of this rule, as I noted, is to harmonize the extent possible FDA’s regulations with the common rule. Now the common rule revised in two thousand eighteen, but even before that in two thousand and sixteen, Congress required the FDA to harmonize the extent possible as part of the twenty first Century Cures Act. Now if you look at the timeline, this proposed rule by FDA was released in September 2022. So you can see there’s a rather slow progress here, but consistent going forward. 

Now this NPRM on the single IRB does not have to follow the timeline of the NPRM on the informed consent and IRB requirements. So they’re separate NPRMs, so they could go on their own timelines throughout this process or, you know, be withdrawn. One could be withdrawn, the other not, etcetera.  

Now the single IRB requirement in the, you know, most basic of the words would require any institution located in the United States participating in FDA-regulated cooperative research. And cooperative research means more than one site, to rely on review and approval by a single IRB for that portion of the research conducted in the United States with some exemptions exceptions. And the goal of this was to streamline the review process, and decrease regulatory burden, as we mentioned, but without compromising human subject protections. And I think a good way to think of this is that single IRB has always been allowed under the FDA regulations and the common rule, but now it will be required. And this has already been passed for the common rule. For the common rule for federally funded research, you must use a single IRB for cooperative research unless an exception applies. So this would be FDA adopting this as well. 

Now what does this mean for you? So if you are a sponsor or a CRO, you will be required to use a single IRB unless an exception applies, you know, by regulation. And if you are an institution or an investigator, you will be required to use that single IRB that is chosen by the sponsor of the CRO. And if you don’t want to do so, then you don’t participate in the research. I mean, it becomes very black and white in that sense. But we do need to talk about those exceptions. 

So in the common rule, there are two exceptions, and I wanna contrast this to what FDA has done. Under the common rule, cooperative research for which more than single IRB review is required by law is an exception. And usually that will be, an American Indian or Alaska Native tribe. It might be a state law requiring IRB review under, you know, some state provision. But in any case, you know, there’s a lot of legal reason to have more than one IRB involved. And the second one adopted under the common rule is research for which any federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular context. 

And I will give a little, heads up to two slides away. 

FDA did not adopt this second requirement because they don’t feel that they are offend they’re not a funding agency. It doesn’t isn’t really applicable to them. 

So what FDA is proposing for exceptions to the single IRB requirement are these four here. So the first one is the same, cooperative research for which more than single IRB review is required by law. Two, cooperative research involving a highly specialized FDA regulated medical product for which unique localized expertise is required, and I’ll talk more about that in subsequent slide.  

And then three and four, cooperative research on drugs that meets the exemptions from an investigational new drug application under three twelve point two b, or for devices, cooperative research on medical devices that meets the abbreviated requirements under eight twelve point two b or is an exempt investigation under eight twelve point two c. So in other words, if you have an IDE for your device research, you will need to follow the single IRB requirements. But if you have a nonsignificant risk device study or you have an exempt device study, for instance, it’s on label, it’s a diagnostic with certain other conditions, then the single IRB requirement will not apply to that research. So, again, what wasn’t adopted by FDA was the federal department or agency supporting or conducting the research. You know, FDA is not a funding agency with very some very limited exceptions, and they just didn’t wanna have a role in choosing IRBs, you know because that is something that’s been assigned to the sponsor or the CRL, not to the agency in the case of FDA.  

But what are these FDA exceptions? I wanna look at that first one again that’s labeled here as number two. Cooperative research involving a highly specialized FDA regulated medical product for which unique localized expertise is required. So what’s interesting about that is there are no definitions of those terms. You know, what is a highly specialized FDA regulated medical product, for instance, and there’s no guidance on who makes this determination. I suppose it’s the sponsor or the CRO. You know, it’s just not stated in the regulation. I think this will be very rare, although, theoretically, it could become a fairly large loophole, kinda like the five ten k clearance process for devices. We’ll have to see how that evolves. 

But, you know, my personal opinion is it will remain, a minor exception. But the exceptions labeled there as three and four, cooperative research for drugs that don’t need an IND and cooperative research for devices that don’t need an IDE. I think that provides an appropriate flexibility. You know, because we ought to phase four research, investigator initiated research. Often, there’ll be small studies. And I think it’s important to remember that you can still use a single IRB if you wish. It’s just not required under the single IRB regulation. 

So moving on from the single IRB. And the main focus here oh, sorry. Same timeline. As you know, two thousand sixteen, Congress required FDA to take this action to harmonize Common rules revised in two thousand eighteen. This rule came out 2022. But I really wanna focus on the consent elements because that’s what’s mostly going to affect all of us involved in the conduct of research.  

FDA proposes to adopt what the common rule has already adopted, and that is that the prospective subject or LAR, legally authorized representative, must be provided with the information that a reasonable person would want to have in in order to make an informed decision about whether to participate and an opportunity to discuss that information. So remember, before this change, the regulation just said, here’s the elements of consent. They must be included. But there was really no statement that you had to focus on making that intelligible, understandable to the research subject. I mean, I said the language had to be understandable, but now we’re really saying we need to focus on the subject here.  

The informed consent must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or LAR in understanding the reasons why or why not one might want to participate in the research. And this part of the informed consent must be organized and presented in a way that facilitates comprehension.  

And then it goes on in the second section there are two and says not just that key information section, but the whole consent document and process must present information in sufficient detail relating to the research and must be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the perspective subjects or legally authorized subject representatives understanding of those reasons.  

So, again, the emphasis here is on getting away from here’s the elements of consent, put them in any old order you want as long as they’re there to make this consent form and this consent process focused on the subject’s understanding and what is important to them. So here’s some things that might be in that key information section upfront, you know, that begins the consent form. Now it should be, you know, two pages or three pages at most. It can be shorter. But for instance, maybe if, if you join this study, you will be unable to receive other cancer drugs in the same class in the future. 

That may be a sufficient reason for somebody to say, you know, I will, skip on the investigational product and take an approved drug in that class. This research will likely make you sterile and unable to have children in the future. That could be very important to certain people. In this study, you will be exposed to shigella and will likely get dysentery. You know, this is for a study where you’re actively exposed to a disease. Very important information that might be, you know, incredibly unpleasant. This study will require in person visits every three months for two years. Now if the clinical approach to this only requires one or two visits, this may be quite a burden for somebody to determine whether or not to join a research study. 

So these are the types of issues that come out. And I should note that OHRP and FDA recently released a draft guidance providing some more, focus on the various types of information that might or might not be relevant in this. It is still draft, but, it is out there. 

So what does this mean for you? Well, if you write consent forms for FDA regulated research, you will have to include the key information section at the beginning of the consent form, and you’ll have to draft that up, because otherwise, the IRB is either going to provide that back to you to fix or write their own, but most likely send it back to you. Now individuals who write consent forms for federally funded studies have already been doing this for several years. They are used to it, and the consent forms we receive for federally funded research by and large have it at this point. 

Now if you obtain consent from research subjects as part of any the clinical setting, you will need to focus on the key information requirements at the beginning of the process and really kinda highlight those pieces of information that will be important to the subjects. And finally, of course, IRBs will need to review the key information section. 

And with that, I’d like to turn it over to Donna Snyder to talk more about the internal workings at the FDA. 

Donna Snyder 

Thanks, David. That was a great summary of those two, rules that will hopefully be issued soon. 

So, I’m Donna Snyder. I’m executive physician at, WCG. I’ve been with, WCG for about a year now, a little less than a year. Prior to that, I worked at the FDA for a little over a decade. And when I left the FDA, I was, leading the pediatric ethics team. I’m a pediatrician by training and I’m a bioethicist. And what I’m planning on talking about today are some of the inner workings of the FDA and hopefully give you a better understanding of why it takes so long for some of these rules to be issued. 

So, rulemaking is actually, defined under the Administrative Procedures Act, and it just negates the process for issuing rules and regulations. This doesn’t just apply to the FDA, but applies to many agencies, and agency management as well as military and foreign affairs functions of the US. It requires a notice of proposed rulemaking, published in the federal register unless the agency finds the notice and public comment are impracticable, unnecessary, or not in the public interest. And we’ll talk about a couple of examples of that on the next slide. 

Interested persons can participate in the rulemaking process by submission of written data, arguments, views, etcetera, to the agency. That’s essentially submitting comments to a docket. But in some cases, there have been meetings that have occurred to discuss, rules and regulations. After consideration of any submitted information, the agency rules, issues the final rule and provides a concise statement of the rules basis and purpose when issuing the rule. So then in general, there’s a preamble to the rule, that you’ll see on the federal register when it comes out. And rules go into effect no less than sixty days from the notice, although many times that I mean, not thirty days from the notice, but many times this will be sixty days, unless, the rule recognizes or grants an exception or relieves a restriction, is an interpretive statement or a statement of policy or for other good cause published with the rule. 

So the two examples where the, NPRM may not be issued would be these here. One the first one is an interim final rule. There may be cases where an agency has good cause to issue a final rule without publishing a proposed rule, But this can be characterized as an interim final rule. The rule becomes effective immediately, but the agency still, collects comments on the rule.  And if for some reason that there was, you know, significant, objection to the rule, then there might, be some changes made. But if no changes are made, a brief final rule will be published in the federal register. And, and one of the most important, examples of this is twenty one CFR fifty subpart d, the additional safeguards for children in clinical investigations that was issued as an interim role in two thousand one and as a final role in two thousand and thirteen.  

As many of you may know, under forty five CFR forty six, there was a sub d talking about, additional protections for children, that was in effect since nineteen eighty three. And in the early two thousands, FDA started issuing, or, Congress issued legislation both the Pediatric Research Equity Act and the, BPC act BPCA act, the better pharmaceutical pharmaceuticals for children act. And because these acts were being, brought forward, it was important that there also be some ethical requirements for, research that, research would be, you know, thinking about as they develop these studies. And then there’s the example of a direct final rule if an agency decides that a proposed rule isn’t necessary because it will relates to routine or uncontroversial matters. It may issue a direct rule. 

The direct rule goes into effect on a certain date unless the agency receives substantive adverse comments during the comment period. And then if the comments necessitate withdrawing the rule, the rule may be withdrawn or the rule could be, reinitiated or restarted as a proposed, conventional rule. And there’s an example that’s here that, you know, I think is fairly straightforward, the direct final rule to revoke use of partially hydrogenated oils in foods in two thousand and thirteen. 

So I just wanted to present this slide here. So in two thousand nineteen, GAO, did a report or review of the rulemaking process across many agencies, or I think there were about ten agencies that were, reviewed in that report, but one of them was the FDA. And essentially, this is what happens when a rule is issued or also when guidance is issued. 

So and what happens first is that it’s the idea that a rule needs to be developed is brought forward. In this case, the prompting at FDA was because of the, change in regulations with the common rule. The individuals at the FDA get together, prioritize plan, think about what they want to put into the rule, They gather information. Generally, this is done in a working group process. Then they develop the language. The language needs to go through both internal and external review by with or review within the FDA and then review by other agencies where the changes that are associated with that rule might have some impact. A proposed rule is published, and then, A proposed rule is published, and then, comments are collected, and those are analyzed. And then the result of that is incorporated into a final rule.  

When the final rule is developed, it also needs to go through this review process both within the agency and outside the agency. And then finally, it’s published as a final rule. And on this slide, there’s the link to that entire report, which some of you may find, to be quite interesting.  

So what delays the process? So, when we’re talking about, rules or guidance, really, they’re both done in the same way. Delays occur between these steps because multiple stakeholders are involved in the process. As I already mentioned, working groups are established to discuss the components of the rule and propose the language for the rule. Relevant offices such as the Office of Clinical Policy, the Office of Medical Policy, Office of the Chief counsel, office of the commissioner might be involved in developing the rule. If other offices might be impacted by the rule, then they’ll be involved in that conversation as well. The proposed rule goes through various levels of review at the FDA. 

If significant changes are made as part of the review process, review may be necessary to assure agreement. Once draft language is agreed upon, a formal review process takes place, and this may include additional offices and stakeholders that may not have been involved initially. Once FDA clearance is complete, interagency review occurs. So it may go to NIH. It often goes to the office of budget and management, our management and budget, OMB. And then other agency priorities sometimes slow this process.  

So for example, during the COVID nineteen pandemic, everything was dropped. All the resources within FDA went towards the pandemic. Guidances were developed as a result of what was happening with the pandemic. And then some of those things were picked up after things slowed down a bit. So, I think it’s important to see how this occurs. 

And I just thought it might be helpful for me to talk about two examples that I had in my role at FDA. I was involved both with the drafting of two guidances, the research involving children as subjects and not otherwise approvable by an institutional review board and the ethical considerations for clinical investigations of medical products involving children. The first one that I mentioned was very procedural in terms of its content, but we did do that with OHRP.  

So as a result, we needed to work with OHRP to develop the language. It took few a few go rounds with that, writing to come up with what worked for both agencies. And then we needed to go through internal review. We often go through a pre review before we go through a review. 

And then after that, we, sent it through all the different groups that might be, impacted by the changes that were associated asked to sign off on it. For the ethical considerations for clinical investigations of medical products involving children or the pediatric ethics guidance, that was actually even more complex. That guidance started out as a guidance that was focused on drugs and biologics. And then as the guidance was being worked through, it became clear that we also needed to include devices in that guidance. 

So we went back to another work group, worked with, CDRH to develop additional language to add to that guidance. And because the guidance was so complex, we found ourselves often when we were looking at one section with one group making enough changes that we thought it was important to take it back to another group. 

So even before we got into the pre review process, we were having a lot of back and forth with groups to ensure that the language that was in the guidance was consistent with all these different groups. It took about five years to do both of those, guidances, and about two years of that was related to, internal FDA clearance. And I think it took about three to four months to clear outside of the agency. But I think it’s important for people to understand that, you know and in this case, there really was no slowdown. Even during the pandemic, we were able to move forward with some of our reviews. 

So, it just takes a long time for these particular guidances to move through the agency. And I think rules are also very similar to that. So we’ll go to my next slide, which talks about the two topics that we were talking about today. So, you know, as we talked about with harmonization with the common rule on a single IRB and waiver of consent, FDA had to consider whether all the changes to the common rule were applicable to FDA regulations.  

And you heard in David’s presentation that there were some areas where FDA thought that there was an alignment and that they should make different recommendations. And, you’ll find this to be true, say, for example, for subpart d under the FDA regulations versus the common rule regulations. There are some subtle differences between those two which are really related to the fact that we’re talking about clinical investigations versus research as a whole.  

And then I think it’s important to remember that once, FDA regulations are finalized, the process for revision of any regulation is very, very slow, even slower than rules. So it’s really important to take into consideration the content of the regulations as they’re being developed.  

And the other thing that has been consistent with what FDA’s done in the past is that FDA generally develop some guidance to kind of fill that void between the time that the rule is proposed and the rule is issued. So the cooperative research information sheet was in place since nineteen ninety eight that really allowed single IRBs and describe the process. 

The impact of certain provisions of the revised common role and FDA regulated clinical investigations was issued in October two thousand eighteen and, and talked about where FDA was willing to, provide or allow some, you know, regulatory flexibility versus maybe wanting, sponsors and investigators to follow the FDA regs.  

Informed consent guidance for IRBs, clinical investigators and sponsors was issued in, August of twenty twenty three. That particular guidance doesn’t have the changes incorporated in it that will be incorporated as a result of the rule, but it basically creates a groundwork for what will need to be in place for those additions to be added. And then, of course, there’s the key information guidance that, David mentioned as part of his presentation. 

And then finally, I wanted to talk about the FDA track, which many people may not be aware of. And this is something that can be found on the FDA website. There’s a track for other agencies as well. So if you search unified agenda, you’ll come up with a broader track that also has other agencies that you can search. But if we go to this next slide, you’ll see what I’m talking about. 

And although I don’t think the  links on these slides will be active, you will be able to just search for this and find this. So if you search FDA TRAC unified agenda, you can search for any rules that might be under development. And in the formal title here, you don’t necessarily have to put the entire title. So I placed institutional review boards in this title, and I was able to pull up both of these, rules that we’re talking about today. FDA is proposing that these will be published in December of twenty twenty four. The one caveat to this though is that FDA can change their mind and update this if they’re not making the progress that they think they need to make in order to issue the rule. And you’ll find this to be true for, you know, other actions that are occurring FDA. You can search for, you know, other things you might be interested in. And then, you know, find out what the date projected date of publication will be. So that’s all I have, and I’ll hand it over to Sandy. 

Sandy Smith: 

Thanks, Donna. So Sandy Smith, senior vice president for clinical solutions and strategic partnering. And my contributions to today’s webinar is really from the perspective of having stood up and managed, local IRBs both for community hospitals as well as for a large SMO. And clearly we know there are challenges in maintaining your IRB. Things like ensuring that you have the right expertise, therapeutic area, modality expertise. Our clinical trials today are getting very complex. Just looking at all of the discussions about artificial intelligence and how that’s going to weigh into clinical trials, ensuring that you have that level of expertise and knowledge is going to be critical. And I think the other challenge always is ensuring that your IRB members have been updated in providing education on the latest rules and regulations. So this is not an appointment that’s made lightly. A lot of thought goes into it. But a lot of work in maintaining those very high standards that IRBs are set up to do.  

So how does that relate to today’s topic? I’d like to chat just briefly on what some of the observations that I’ve had inworking with sites as they are anticipating the final ruling coming to fruition. I think many sites approach these notices in a different way. Some are jumping on it more immediately and saying, this is likely going to come into fruition therefore how do we get this on our work plan and begin putting timelines associated with it. Other sites are kind of saying, yep. We are aware of it, but we’re just gonna hang back a little longer because we’ve got a lot on our plates and certainly research sites do have a lot between technology and other initiatives that they’re undergoing. But I would say, being mindful about this as part of activation times and clearly there isn’t a single site that I speak with that doesn’t refer to a process improvement or a laser focus on their activation timelines. 

As we interact with sites we hear some that are activating clinical trials in less than thirty days, and then others that are well beyond three hundred days, and we know that IRB just fulfills one part of that process. So as you begin to look at metrics and breaking down what part does each aspect or each task within activation, contribute to the overall timelines? IRB is one. Are sites working on IRB in a concurrent manner with other activation tasks, or are they doing concurrently? But at the end of the day, kind of looking at, lot of I think as we talk to sites too, we also hear a lot of angst about how they can how they can navigate their local requirements.  

Many times when we hear new regulations come out, I’ll call them band aids, you know, they’re being reviewed and we’re modifying SOPs to some degree to accommodate the new regs. I might suggest you take this as an opportunity to really back up and look at what your local requirements have been and pressure test them. Are they really needed today? Maybe things were written into policy years ago that may not have as much emphasis today, particularly with the move to a central IRB. So take that as an opportunity to really explore what those local requirements are before doing slight amendments and accommodating those within the workflows. And as you know, we can set up local process rules. So collaborating with whomever the central IRB provider is that you’ll be working with so that they understand what your local requirements are. But again, I would really suggest pressure testing, what has been the past for what might be needed in the future. 

And then as you’re looking at your overall activation timelines, you know, know what those activation timelines are from the central IRBs and account for that into your workflows, into your metrics. And I would say not just IRB but IBC since there’s such a surge of cell and gene therapy trials that would also require the IBC review I’d suggest you start early. Don’t wait for that final determination to come because then it feels like it’s just one more clock that’s ticking in the background. So if you can begin having those conversations early as many sites have had. We know and believe that this will add efficiencies. We know that it will make it much easier for the sponsor, but we also believe it’s going to be easier for the sites as well. And again, looking at it earlier rather than later. I know that many organizations are metrics driven as we are as well. And there was some data that was presented in a poster session at AACI last year where the University of Michigan actually used Six Sigma processes and they looked at internal workflows when they use their internal IRB. And they also looked at using a central IRB and found that the amount of time that their regulatory team members contributed was less when using a central IRB. So that was a publicly published, poster, again through the AACI website, I might encourage you to take a look at that. But, overall, we do believe that this will add efficiencies. It will reduce activation timelines and hopefully be easier for your team members. But there’s work in in working out all of the workflows. 

So just in summary, the clock is ticking. Find the right partner and begin having the discussions and conversations, but we do believe this will be a significant contribution within our industry.  

Alright. Now I think we’re gonna be moving on to our q and a.  

Craig Rotzler: 

Thank you very much, Sandy, and, thanks to, David and Donna as well. We’ve received a ton of questions. So if you don’t get to your question, rest assured that we will be, responding to everybody, everybody’s questions or creating some sort of FAQ that we’ll send out to everybody as well. So please do put your questions in the q and a, so we have those for reference. 

Our first one, and feel free for anyone to jump in, is the only this is only in cases of federally funded research. Is that correct? In keeping with, the common rule. 

David Forster: 

So the common rule does apply to federally funded research and to, you know those changes have already been made to the common rule that we were discussing today. The  goal here is for the expectations that FDA will also adopt these requirements, and then it won’t matter whether it’s federally funded as long as it’s FDA regulated. 

Craig Rotzler: 

Thank you, David. Next question asking to confirm, sites which have previously selected their own local IRBs versus central IRB would only be able to do so if they meet the expectations. Is that correct?  

David Forster: 

Meeting one of the exceptions, perhaps? Yeah. You if you have a local IRB, you will not be able to use it once FDA adopts the single IRB requirement unless one of those exceptions apply. And if the exception does not apply, the local IRB has no role in the review of the study. 

Craig Rotzler: 

Thank you. And our next question asking or stating that I assume that sites with local IRBs would have to follow their local IRB requirements, to see approval still. That will be have this requirement. Is that correct? 

David Forster: 

Yeah. That will be an internal decision for the institution. They may still wish to have a process why bit whereby their local IRB decides whether or not they can participate, but the local IRB won’t be able to say no. If the site does participate in the research, they will have to use the single IRB. 

Craig Rotzler: 

Okay. Does the single IRB requirement apply to only studies overseen by the FDA, or is this all studies? 

David Forster: 

Yes. It is this will be FDA regulated studies. And, again, the two big exceptions are the carve outs for drug studies that don’t need an IND and for device studies that don’t need an IDE. So quite those are still FDA regulated, but they’ll fall under the an exception from the requirement for single IRB. 

Craig Rotzler: 

Okay. Who makes the decision whether a study meets the criteria for the exceptions? 

David Forster: 

That is not stated. Now the IND and the IDE exceptions are pretty black and white. I mean, you either need an IDE or you don’t. Right? And, I mean, it’s not always sort of in an easy decision. It’s often quite difficult decision. But, you know, you end up with a definitive answer, and at the end, if you can’t decide, you go to FDA and ask. So those two are quite objective. The one about the localized specialized knowledge for, you know, unique FDA product, that one’s really kinda wide open. You know, we don’t know who makes that decision, and we don’t have any definitions for the terminology. 

Craig Rotzler: 

Okay. If a single IRB is appointed by sponsor CRO, could there be an issue with conflict of interest? 

David Forster: 

I don’t think it enhances the conflict of interest any more than it currently exists. I mean, IRBs and CRO excuse me. Sponsors and CROs at this point choose IRBs to be the central IRB. They can’t even choose one to be a single IRB and not allow other IRBs to participate. So I don’t think it makes any change in the status of the conflict of interest. 

Craig Rotzler: 

Okay. Does the single IRB rule mean that two institutions collaborating on a study or trial only need to use one IRB? 

David Forster: 

Correct. K. 

Craig Rotzler: 

This person is stating many larger research institutions, especially as those affiliated with universities, mandate that their institutional IRB be used. How do we, handle the situation for a multicenter study where the remainder will accept a single IRB but are not subject to the university IRB jurisdiction? 

David Forster: 

Not sure. I completely understand the question, but I basically the local IRBs will no longer have the authority to say that they must be used. Now they could do a secondary review that won’t have any regulatory standing. You know? So there could be a an institutional vetting process. And, of course, there often is. You know? Do we have enough nurses on staff to do this? Do we have the appropriate pharmacy facilities? So there’s all sorts of reason institution may not decide to, engage in a particular research study. But the IRB will not be able to say local IRB will not be able to say, well, you’re using us instead of the single IRB. 

Craig Rotzler: 

Go ahead. 

Sandy Smith: 

And if I could just add to that, I think at the end of the day, as any new regulation is released, what sites and institutions need to do is to look at their local policies and SOPs and make the appropriate amendments. This is one it’s really no different. 

Craig Rotzler: 

Great. Thank you. Does this have any effect on organizations that use a local IRB for administrative or courtesy review? 

David Forster:  

No. 

Craig Rotzler: 

K. And can you confirm that there is no exception that local IRBs can still review, but no payment would be given for local review if institutes require it? 

David Forster:  

Can’t speak to the payment issue. Again, local IRBs can do an administrative review if they wish, but it won’t be the IRB that is officially in charge of the study. 

Craig Rotzler: 

Okay. Regarding single IRB regulations, have institutions provided feedback to the FDA? Often in the past, regardless of having a central IRB or single IRB, many institutions still require their own IRB to review the study and documents. Will the institution still be allowed to do this? Will sponsors be able to bypass the institutional requirements, or will this just add cost, resource, and time to get studies up and running? A lot a lot packed in there. 

David Forster: 

Yeah. If an institution does choose to continue to require local IRB administrative review, if we wanna call it that, that would add administrative burden. The whole idea behind this regulation in the common rule and with FDA is to is to lessen administrative burden. That was the stated goal of these proposed notice of proposed rulemaking. So, I mean, it has the potential to increase it based on institutional policies, but the goal was to decrease administrative burden.  

Donna Snyder: 

And I would just add that, you know, if some of these agencies or these groups, submitted comments to the FDA, that the FDA would have considered them and looked at whether or not they were applicable to the regulation. But essentially, FDA was, goal was to harmonize as much as possible with the changes in the common rule. So they might have considered how this might have impacted these institutions, but we’d move forward with, making as many changes that were consistent with the common rule as feasible based on FDA regulations. 

David Forster: 

Right. And if you if you remember the twenty first Century Cures Act, it was a very broad bill that took years to be put together. And this IRB part of it was a very small part. There were lots of other go lots of other measures taken to help streamline the conduct of clinical trials. And one of them was people complaining about, you know, there’s all these IRBs, and, the regulations are distinct between the common rule and FDA. And, you know, it would ease the regulatory burden if they were harmonized. So know, this goes way back to a congressional direction to try to make this as simple as possible. 

Craig Rotzler: 

Great. Thank you. 

Sandy Smith: 

And Craig, I would just add, I encourage you to really think about this, have the discussions with your leaders of the IRB. And again rather than inserting this language, this requirement, and then continuing to do business as usual, really take the opportunity to ask questions as to whether certain workflows and processes still are as important today as they have been. There may be ways to simplify those workflows. 

Craig Rotzler: 

Excellent. Thanks for chiming in. David, you mentioned that you have an IDE for the device you’re required to have a single IRB. Can you correct me, but then stated that, non IDE not needing nor required to have a single RB. Is that correct, or did we misunderstand that? 

David Forster: 

Correct. No. If a device study has an IDE, is required to have an IDE, you know, application, then the single IRB requirement will apply. But if it’s a nonsignificant risk study or if it’s an exempt study from the IDE requirements, and there’s a couple of those or some certain diagnostic devices don’t need to have an IDE. If a study is on label with an approved device, it doesn’t need an IDE. So there are these other exceptions. In those cases, the single IRB requirement will not apply.  

And I think I saw something in the questions about an HUD. You know, there’s a couple statuses for HUD, three. But as long as that HUD, humanitarian use device, which is for small patient groups where they just wanna get the device out there to help these small pie patient populations, those HUDs that are not under an IND will not fall under this single IRB requirement. 

Craig Rotzler: 

Okay. Great. Thanks. Would post approval studies be exempt from the single IRB rule? 

David Forster: 

You know, the question is gonna be whether it’s post approval or not. Does it need an IND or an IDE? Now most of them won’t, because they’re already approved. But if, you know, you change the indication or something like that, then you could fall back into the IND or IDE world. And so then the single IRB requirement would apply. But by and large, I don’t think they will. 

Craig Rotzler: 

Okay. If we are starting a new IDE study this year, will we need to use the single IRB for all sites, and will WCG be updating their ICF template? 

David Forster: 

Donna, you wanna take that one? 

Donna Snyder: 

Well, I would imagine that, you know, they would need to follow the single IRB rule for all sites. I don’t know that, you know, I don’t know how this impacts the ICF templates. So, David, you can, comment on that because, you know, I think we’re already incorporating, using key information as part of the, ICFs anyway at this point in time. But there may be changes that I’m not aware of. 

David Forster: 

And I and I think another point to make about that is if the single IRB rule has not been released yet, you do not need to use the single IRB before that. I mean, there’s kind of a couple of things in that question.  

Donna Snyder: 

So That’s, yeah, that’s an important point. Right. Yeah. Right. 

David Forster: 

Studies will be grandfathered in until the point where the rule is actually issued. 

Donna Snyder: 

Exactly. 

Craig Rotzler: 

Next question. What about additional institutional, institutional additional boards such as radiation boards, etcetera, that may locally require additional review? Will the single or central IRB also be responsible for these additional reviews? 

David Forster: 

No. They won’t. All those separate auxiliary processes will continue to operate, and they’ll still need be the need to get any consent form requirements or other limitations on the research in front of the single IRB to take care of it. So for instance, if you have a conflict of interest committee or an IBC and they want to change a consent form, that will still have to be considered by the single IRB. 

Craig Rotzler: 

Okay. What are the expectations for the single IRB timeline? The requirement had significantly longer time between when OHRP used the issued the twenty eighteen revised regulation and when the SIRB took effect? 

Donna Snyder: 

I can answer that one. According to the unified agenda, it should be issued in December of twenty twenty four.  But, obviously, that’s a proposed timeline, and the FDA is not required to meet that timeline. And, you know, I think there was a lot of discussion internally about what the exceptions might need to be, that may have delayed, you know, the, issuance of the final rule.  

Craig Rotzler: 

Thank you. Does this rule only apply to new studies? 

David Forster:  

Yeah. The old studies will be grandfathered in. You don’t have to worry about until it is actually issued both of the NPRMs.  

Craig Rotzler: 

And what does the use of single IRB mean for local IRB on the institutional level? 

Sandy Smith: 

You know, I think that depends on the scope of the IRB for that institution. This talks about a subset of studies multicenter sponsored trials, going to a central IRB. All trials outside of that scope can continue to be, managed at a local IRB level.  

David Forster:  

And, you know, like a large universities, etcetera, there’s a lot of research that’s not federally funded or FDA regulated. It would not require single IRB reviews. So all the student research, a lot of psychology, you know, various other things. There’s a very large body of research that will not be affected by this. 

Craig Rotzler: 

K. With the new requirement, many sponsors and CROs will prefer the central IRBs. What has WCG done in in others to accommodate the influx of new trials coming through central IRB? 

David Forster: 

You know, we’re ready for more trials. You know, we have pretty flexible processes in place and capacity. It’s not really you know, currently, a lot of these studies come to us with certain sites being reviewed under their local IRB, but we will be the central IRB. And same with Advarra and the other independent IRBs that are out there. So it’s really not gonna change our role too much other than that there will be no sites that are outside of our review. So that that’ll be the biggest change. 

Craig Rotzler: 

Great. Can clinical trials and other clinical research be approved by the same IRB?  

Sandy Smith: 

The same meaning as central? 

Craig Rotzler: 

Not sure. Yeah. 

Sandy Smith: 

I can Yeah. Well, clearly, central IRBs can review any type of research. Again, for the purposes of today’s call, we focus just on the multicenter sponsored trials. 

Craig Rotzler: 

Yeah. 

Daivd Forster:  

And one of the points I had made is that, you know, this new single IRB requirement is a requirement. Right? You have to use a single IRB if the regulation applies, but there’s never been it’s never been disallowed. Right? You’ve always been able to use a single IRB if you wish in the past. 

Craig Rotzler: 

Okay. This person states the implementation of the revised common rule did not include how the IRB of record administered the protocol, for example, rolling review and approvals, groups of five sites being reviewed and approved at the time, at its excuse me, at a time Every single IRB I’ve worked with has been different. Is the FDA providing more guidance regarding this? 

Daivd Forster: 

No. I don’t think so. This does not cover how the IRB goes about adding sites or, you know, designating the continued review date for those sites. 

Craig Rotzler: 

K. And if our site is a sponsor, could our local IRB serve as the IRB of record? 

Daivd Forster: 

Yes. Many of the larger academic IRBs have set up processes to be central IRBs or single IRBs, and have been doing so. And there’s, you know, there’s a lot of good work that’s being done on how to go about that and how to allocate the appropriate resources. You know, Smart IRB has done a lot in that area. AARP has, you know, kind of provided guidance on how to go about it. So it that is definitely an option.  

Craig Rotzler: 

Perfect.  Will this affect what IBC can be used? 

Daivd Forster: 

No. 

Craig Rotzler: 

Can the single IRB of the local IRB of one of the participating sites, can it be one of the participating sites, or does it need to be a central IRB? 

Daivd Forster: 

Not sure I understand that one completely. 

Craig Rotzler: 

Oh, I’ll reread it. I may have messed it up. So can the single, excuse me, can the single IRB be the local IRB of one of the participating sites, or does it need to be the central? 

Daivd Forster: 

Yeah. No. It absolutely can be. They just they will have to become the central IRB. And I think what’s important for an institution to think about if they want to be a single IRB is having the appropriate SOPs and technological processes in place to have different consent forms, to consider different state laws, to consider local considerations at each of the different sites. And so it’s just kind of a change in the IRB’s processes to be able to take on that capacity. 

Craig Rotzler: 

Thank you. And will the local IRB be able to make changes to consent to suit the local population in addition to the boilerplate? 

Daivd Forster: 

They can submit it for the single IRB’s consideration, but they cannot unilaterally make those changes.  

Craig Rotzler: 

And is WCG still going to require that local IRBs give a determination notice to submit to them? 

Daivd Forster: 

No. I don’t think we will have to. Although, you know, actually, we may keep that process in place because of the exempt studies or the exceptions. Right? If you have a non IND or non IDE study, we would still want to know that the institution has made is acceptable with us being the single IRB. So I think, you know, on a more limited fashion, but I think that process will still be in place. 

Craig Rotzler: 

Okay. Will active FDA regulated studies need to update ICFs? 

Daivd Forster: 

No. They will be grandfathered. 

Craig Rotzler: 

This person states, at our institution, we are man mandated to use a separate standing HIPAA for and edit the consent templates for our institution. This is reviewed by our local IRB and then sent to the central IRB of record. Would we still have this option? 

Daivd Forster: 

Yeah. That makes perfect sense. I mean, the have the forms and, of course, a single IRB should be willing and capable of having individual consent form elements, you know, for conflict of interest, for Catholic-based institutions, for compensation for injury. You know, there’s a lot of individual institutional requirements that do need to be considered by the single IRB. 

Craig Rotzler: 

Great. Will EAP or extension studies fall under single IRB rules? 

Daivd Forster: 

They usually, it’ll depend on whether they have an IND or not. I hadn’t thought of that in preparing for this. Donna, do you know off the top of your head? I can’t remember if EAPs… 

Donna Snyder: 

Expanded access expanded accesses have INDs. 

Daivd Forster: 

So Then Yes. Then the single IRB requirement will apply. You know a lot of expanded access are individual, and those obviously are not cooperative researchers, not more than one site. So those will not need the single IRB and, you know, it’s only one it’s just one individual getting the product. You also have bridging, you know, the bigger expanded access protocols that provide for multiple groups, and they will have an IND. And so and they will be cooperative research. So, yes, those it will be under single IRB. Unless FDA says something different when they issue it.  

Craig Rotzler: 

Many of the reliance agreements with external IRB include provisions for the institution to retain responsibility for some components of the research, training of personnel, local contacts consideration, etcetera, Will the single IRB rules have any impact on reliance agreements? 

Daivd Forster: 

No. I don’t think so. It’s just it’s kinda like it’s just the way it was. You could use a single IRB. Now you must use a single IRB in these certain types of studies, but all of those types of contractual issues and rules should not be changed by this. 

Craig Rotzler: 

And how do you see this impacting academic site participation in trials? 

Daivd Forster: 

I think that a lot of academic centers will rely on a single IRB. And as I mentioned previously, many of them are establishing themselves to be single IRBs. So I think it’s gonna depend on each institution deciding whether or not they want to take on the role of being a single IRB, and those that don’t will need to outsource these type these given studies to a single IRB, which may be an independent or it may be another academic institution whose IRB has decided to take that role on. 

Craig Rotzler: 

Alright. And if our site only uses central IRBs, would this still apply to us? 

David Forster: 

Yes. I mean, it’s just a requirement to do so rather than being allowed to do so. 

Craig Rotzler: 

Okay. If we have institutional local IRB with smart IRB access, will institutions still be able to utilize smart IRB access, or will it only be single central IRB with no local smart IRB access? 

Daivd Forster: 

Well, the smart IRB is an agreement whereby you use a single IRB or another IRB. And most of the single IRBs that are out there have adopted the smart require the smart IRB requirements. So I think that smart IRB requirements and, you know, the various joiner documents, etcetera, will not be affected by this. It fits it fits into the process. 

Craig Rotzler: 

Alright. That is a whirlwind of questions. I think we’re gonna end it there. Again, if we were not able to get to your question, don’t worry. We’ll respond to you and provide, some additional feedback for you. Just wanna thank our panelists for joining us today and our speakers, and our participants for you all for joining us today as well. Please, do follow-up survey after we end this webinar. It should pop up on your screen. So really do appreciate you spending the time here today, and I hope you join us again in a future webinar.