Based on AHLA’s annual Health Law Connections article, this special series brings together thought leaders from across the health law field to discuss the top ten issues of 2023. In the tenth episode, Tynan Kugler, Principal, PYA, speaks with Rebecca Schaefer, Partner, K&L Gates LLP, about research-related policy initiatives and regulatory changes to watch. They discuss the FDA’s September 2022 Noticed of Proposed Rulemaking, Biden Administration initiatives including the Cancer Moonshot and investment in cancer-focused clinical trial networks, the efforts of the newly formed Advanced Research Projects Agency for Health, and developments related to Presidential Memo 33 on research security. Sponsored by PYA.
Watch the conversation here.
To learn more about AHLA and the educational resources available to the health law community, visit americanhealthlaw.org.
Based on AHLA’s annual Health Law Connections article, this special series brings together thought leaders from across the health law field to discuss the top ten issues of 2023. In the tenth episode, Tynan Kugler, Principal, PYA, speaks with Rebecca Schaefer, Partner, K&L Gates LLP, about research-related policy initiatives and regulatory changes to watch. They discuss the FDA’s September 2022 Noticed of Proposed Rulemaking, Biden Administration initiatives including the Cancer Moonshot and investment in cancer-focused clinical trial networks, the efforts of the newly formed Advanced Research Projects Agency for Health, and developments related to Presidential Memo 33 on research security. Sponsored by PYA.
Watch the conversation here.
To learn more about AHLA and the educational resources available to the health law community, visit americanhealthlaw.org.
A H L A is pleased to present the special series highlighting the top 10 health law issues of 2023, where we bring together thought leaders from across the health law field to discuss the major trends and developments of the year. Support for A H L A in this series is provided by P Y A, which helps clients find value in the complex challenges related to mergers and acquisitions, clinical integrations, regulatory compliance, business valuations, and fair market value assessments, and tax and assurance. For more information, visit pya pc.com.
Speaker 2:Good afternoon, this is Tynan Kugler. I'm a principal with p y a, and I am here with Rebecca Schaffer of k and l Gates to talk about research related developments to watch. We are number 10 in ALA's top 10 issues in health law for 2023, and I am delighted to be here to talk through a lot of e exciting developments with Rebecca. So before we get into it, I'm gonna turn it over to you, Rebecca, and just have you introduce yourself as well.
Speaker 3:Thanks, Tynan. And it's great to be here with you and thanks to the listeners. Um, yes, it's, it's fun to be bringing up the rear in, uh, the 10th of the 10th part of the series. Um, so yes, as mentioned, I'm Rebecca Schaffer, um, a partner in the healthcare and f d a practice group at k o Gates, and I'm a healthcare and research regulatory and transactional lawyer. Um, I'll also just mention before that I was formerly in-house at an academic medical center and had responsibility for, among other things, um, the clinical research program and supporting research administrative offices. So that gave me a, a bit of a front row seat to some of the operational issues that, that research institutions face and will face in implementing some of the changes we're gonna talk about today.
Speaker 2:Yes. And, and I'm, I'm glad that you mentioned for our listeners and also grateful to a H L A for helping put this on, but what, why don't we just dive right in and, and talk about, uh, some of the items that you wrote about. The, the nice thing I think about your, your article was you hit on five or six sort of topics, and one of the thing that's that's been exciting about sort of where we've landed in this podcast series is there have even been some, I would say, some focus on some, some additional developments, uh, refocus on some things that you had written about. So look forward to hearing about those. Um, you know, when I think about research and we, we talk about changes in research, we know that sort of year over year there are, um, hot topics that come up and there are developments, um, that come through a variety of different ways, whether it's policies, rules, statutes, and I'm, I'm curious to know when, when you sort of think, look big picture, you know, what kind of policy initiatives sort of come to mind when you think about 2023 overall?
Speaker 3:Sure. So yeah, and you're right that there have been some, um, developments even since the article went to press at the end of 2022. I'm glad to highlight those here. And I think, you know, a, anything in this space, uh, that deals with a little bit of alphabet soup, so one of those, um, uh, new updates would be fedora and we'll, we'll come to that in a moment. But the, um, you know, f d a, um, omni thebus legislation, but really, uh, starting first on the regulatory front, and this was covered in the article, um, you can give, you know, a little bit of a what to watch for add-on here. But, um, the FDA's notice of proposed rulemaking that was put forward in September of 2022, um, is one example of, um, some regulatory changes afoot. Um, and FDA's intent to streamline and clarify, um, including as most required under the 21st Century Cures Act, certain requirements for clinical investigations and for cooperative research mm-hmm.<affirmative>, Um, you know, as listeners are likely aware, there's two primary regulatory frameworks governing human subjects, protections and research. There's the federal policy for the Protection of Human Subjects, which is colloquially known as the common rule, and that obviously applies to federally funded human subjects research. And then the F FDA rules under 21 C FFR parts 50 and 56, which apply to clinical investigations regulated by F fda. And the challenge is that if you've got federal funding for an f FDA regulated study, both sets of rules apply. So folks were eagerly awaiting, um, the, the harmonization, um, PRO proposal from F D A, which which does, um, take a number of steps towards, um, reconciling their requirements with those of the common rule, for example, um, adding elements to inform consent. Um, and, and interestingly, um, specifically around, um, or at least what I took note of, was, um, informed consent requirements pertaining to subject samples, um, and the impact that's got potential to have on, um, use of samples for whole genome sequencing, which is, you know, an activity gaining interest in speed given the potential for genomic data to, to drive drug target discovery. Um, so, so that's just, you know, one aspect where, um, there were informed consent and IRB requirement updates through the harmonization prong of these, this two-part notice of proposed rule making. What I'll call out though is there were a couple of things F D a declined to, to propose in, in the nature of harmonization. Um, one was, it, it was not proposing to lesson requirements for I IRB review of in vitro diagnostic studies using leftover de-identified specimens, um, where, and that oversight is retained at least in the FDA proposal, whereas the common rule considers those activities as non-human subjects research. And the other call out from that, and then I'll just briefly mention the cooperative, um, research component of the proposed rule, um, is F FDA did not propose to adopt broad consent. Um, and that probably reflects the reality that many research institutions have not utilized broad consent flexibilities under the revised common rule. And that just relates to administrative difficulties created by mm-hmm.<affirmative>, meaning the track subjects we decline and ensure they're never included in studies for which, um, there's a waiver of informed consent, so that, that's on the harmonization side. And then on the, um, single IRB review side, which was the companion notice of proposed rulemaking from F D A at the end of last year, would require, um, a single IRB for all US sites participating in f FDA regulated cooperative research. But it does have a number of exceptions for I n D exempt studies, non-significant risk device studies and IDE exempt device studies. So, just to wrap up on this topic, um, you know, a number of, uh, research institutions and other organizations, including the Double A M C, have commented, and I think we can anticipate the final rules to have clarifications based on those public comments when they're released, um, timing, T B D, um, so<laugh>, you
Speaker 2:Know, yeah, that was gonna, that was gonna sort of be my next question is, you know, everybody, everybody always wants to know, um, when is this gonna occur? Could, if you had a crystal wall, could you say, here's what, here's what we're thinking. Little bit of a loaded question, I know for you. So would be interested to know if you think that's something we're gonna see in, in 2023, or should we, should we, uh, add this to, uh, top 24 issues<laugh>
Speaker 3:Revisit this time next year? Right. Yeah. So I think, you know, FDA missed the notice of proposal making deadline required under the CURES Act by about three years. Um, and, and also just at the lengthy process to arrive at the revised common rule in 2017 is instructed it, it may be sometime before we see the F D A final rules on this. Um, but, but what I'll be watching for, I mean, when, when, whenever they do come out mm-hmm.<affirmative> is, um, whether they increase or decrease the daylight between the F D A, you know, parts 50 and 54 and the common rule, um, because there are some competing considerations between issues that are discreet to F D A regulated clinical investigations and the desire for harmonization. But, but when they do come out, um, you know, I think folks will experience a similar processes when the revised common rule came out. They'll, you know, take a look at their human subject ethics program, standard operating procedures, their IRB reliance agreements, their informed consent templates, and, you know, consider any updates that are indicated.
Speaker 2:Great. A lot to kind of look out for there. So, um, kind of continuing down that f d A path mm-hmm.<affirmative>, um, were there any other sort of changes to touch on as it relates to the, the, the Omnibus Appropriations bill? Anything there? I, I, I know, um, that was one, maybe that wasn't touched on as much in the article, but curious to kind of hear what's going on on that front.
Speaker 3:Sure. Thanks. Yeah. So, um, this was signed into law after the article went to press. Um, it was, uh, December 29th, 2022 is when President Biden signed the Consolidated Appropriations Act, um, which included the Food and Drug Omnibus Reform Act fedora. Um, a few places I'll just highlight that are relevant to the research community. Um, one is section 36 0 1 of Fedora, um, that requires clinical trial sponsors to submit diversity action plans, um, for certain late stage drug trials, including all phase three trials, um, and as well as most device studies. But this is all in the vein of promoting clinical trial diversity. Um, and those action plans need to state goals for enrollment rationale and, and really an explanation of how the sponsor intends to meet those goals, um, for what to watch for on that front. Um, FDA is tasked under the law with updating guidance on diversity action plans, uh, for clinical studies and also hosting public stakeholder workshops. Um, so, you know, if folks are interested, they could, uh, watch the scheduling of those and participate. The, the one other thing I'll, um, call out from Seora is, um, the amendments to the accelerated approval framework under the Food, drug and Cosmetic Act. Um, with these changes, F D A will be required to address, um, among other things, post-approval study requirements for sponsors, um, marketing products approved under an accelerated pathway. Mm-hmm.<affirmative> and the law gives FDA enforcement authority for sponsors failure to conduct those post-approval studies with due diligence or to timely submit reports. Um, so the, the clinical trial diversity and the accelerated approval pathway are just two of, you know, number of changes impacting clinical research in the Omnibus Bill, I, maybe one last call out, um, is the, the law expanded FDAs are really clarified FDA's authority to conduct biomonitoring research inspections, um, e expressly permitting inspections of facilities involved in the preparation, conduct or analysis of clinical and nonclinical studies that are submitted to the F D A, which is just a heads up, um, that this, you know, it scope could reach, um, an increase or result in, in an increase in the number of F FDA inspections of research sites.
Speaker 2:Yeah. That, that's, you know, that's a lot of, you know, so much of it is, is, um, you know, news that results, it's interesting about the, the, um, the acceleration with, with Covid and, um, you know, I've always sort of harken back to get your house in order from the standpoint of having, having everything in place if, if somebody shows up at your door and making sure that you, you understand that you have every, every have everything, uh, as it needs to be. So one of, one of the other things that, you know, I know you and I have talked about, um, leading up to this, is just all of the exciting things that are, are coming up around in particular, uh, the Cancer Moonshot Initiative and some of the things that, that were further honed in and discussed in, uh, the state of the recent State of the Union address. And, you know, one of the things that was just fascinating to me in that part of, in the transcript that came out after that was, you know, the fact that the goal there, there's some, you know, pretty lofty goals, but you can also sort of see that there've, there's been so much good progress in this space and the renewed focus, but you know, that the goal to, to cut cancer death rates, um, in half, um, or at least by half in 25 years, I, it is one of the, the items that was, was put forth, and, and perhaps this is another area you can touch on, is that there were also, there was also the mention of the fact that there are like 30 new federal programs, policies, um, resources, all kinds of things that are coming out around, um, some of what was was, was discussed in that State of the Union. So be curious to know from a research perspective and sort of from your purview, what, what you think we're gonna see there that, that maybe kind of hot off the press too from, from, from when the article was published.
Speaker 3:Right. Yeah, appreciate that. And yeah, I agree. You know, really lofty, um, and laudable goals, you know, put forth in the February 7th state, the union address and, you know, aim high<laugh>.
Speaker 2:Right.
Speaker 3:Um, so, um, yeah, this is a continuation of a policy initiative really, um, begun under, um, president Obama's administration when, when now President Biden was vice president. And, you know, as noted right, it's, uh, a mission to accelerate the fight against cancer mm-hmm.<affirmative>. Um, and so part of the announcement at the State of the Union was, um, reigniting the initiative with renewed White House leadership. You know, I think President Biden's described it as pulling together a, a cabinet specific to this, um, focus mm-hmm.<affirmative>. Um, and one of the things that's a call out and, and getting back to your question about where, you know, funding can be anticipated or how to watch for, you know, what this means in practice for specific programs that, that spin out as part of the initiative. Um, the, you know, important thing to note was that the, um, 2016, um, appropriation are really, uh, funds made available in part for this initiative under the 21st Century Cures Act were, um, 1.8 billion. Um, and there's, um, you know, expiration, an expiration data this year on, on residual funds from, from that initial appropriation. And so in the state of the Union, president Biden, um, urged Congress to reauthorize the National Cancer Act mm-hmm.<affirmative>, um, and, and the White House's articulated support for, you know, another bipartisan effort to build, and this is in particular to you, where are we gonna see some investment, um, cancer focused clinical trial networks? And I think this is, you know, in part consistent with some of the other clinical trial diversity, um, initiatives, companion and other veins of the administration. Um, but, you know, desire for clinical trial networks that reach every community, um, ensuring that we've got representative populations, um, we're reaching, uh, folks in, in all, all areas of our, our, um, community to holistically and, and, um, in a represented way be, you know, striving for innovation in, in cancer therapies. Um, so yeah, that, that, that's, that would be my one call out, uh, for, you know, clinical trial networks is gonna be, I think even, um, an an area of increased, um, investment.
Speaker 2:Yeah. And you know, it's funny that you now sort of putting sort of two and two together. I think one of the things that we've seen a lot of is on the, essentially the academic medical center side where you've got really strong clinical research infrastructures. The, the number of affiliations that are occurring and, and attempts to build relationships out in the community is probably part and personal related to some of what you've described. So, um, be interesting to see how that, uh, how that continues. So you mentioned a, a cabinet being potentially created or created, and I think there are, there's, there are other agencies and other organizations that are also in development from a creation standpoint, one of which is ARPA h. So give us a little insight on that.
Speaker 3:Yeah. And we just, you know, keep going with alphabet suit, right,<laugh>. So, ARPA H is the Advanced Research Projects Agency for Health. Um, and this is a, a fledgling agency presently, um, nestled under N I H, but it's director reports directly to Secretary Erra. Um, it's, its goal is to drive transformational health research innovation and encourage, um, cross-sector and large scale study, um, primarily, uh, targeting potential cures for diseases such as cancer, again, um, Alzheimer's diabetes. Um, and really it's meant to, um, be a disruptor in some ways to traditional means of accomplishing, um, research and really, uh, achieving translation of discovery into, um, real world use clinical applications. So, awardees for arpa h um, you know, funds are meant to tackle new ways to achieve, achieve high impact biomedical and health research. Again, that can't readily be accomplished through traditional, um, research or commercial activity. The, um, appropriation for, um, through fiscal year 22 and, and the funds are available through September 24, um, is 1 billion. And just this month, I'll flag, you know, one, one of a number of announcements, um, coming outta arpa ARPA h but on February 10th, the agency, uh, launched an effort to speed public-private partnerships, um, designed to more rapidly transition biomedical discovery into the real world. And that's, um, contemplated to happen through partnership intermediary agreements, um, and that make transition resources, again, bringing discovery to market essentially available throughout the entire program lifecycle. In other words, get, get parties planning for real world translation from the beginning. Um, and so the, the agency's announcement, um, suggested that these, uh, PIs partnership intermediary agreements would be established with nonprofit partners who have a track record of commercial sector and transition expertise. Um, and they would engage academia and industry on behalf of the agency, the speed solutions to market. Um, so just for what to watch for here, uh, I think, you know, there are, are bills currently under consideration, additional funding under consideration that would further clarify and, and codify and support the role of this new agency.
Speaker 2:I, I think we, we've got time for probably one more topic. And how about if we, we leave the alphabet, we sort of did the reverse alphabet there,<laugh>. Um, but let, let's leave the alphabet and go to, uh, numbers and, um, talk finally about, uh, presidential memo 33 and, uh, the developments that, that are around that and some of what we think we can expect to see there.
Speaker 3:Sure. Yeah. Happy, happy to switch gears to the, um, foreign influence space and, and then we'll bring it home. Um, so, you know, as I think this audience would be familiar, familiar, the, um, presidential Memo 33 is focused on securing, um, federally funded research and development from a national security perspective. And there was an implementation guidance that was released in January of last year, um, that informed, um, oversight expectations and requirements for research institutions to ensure, again, national security of government funded r and d. Um, the, the guidance, you know, wrestles with a tough balance between and, and articulations in the presidential memo. And, and, you know, all around this re recognize a tough balance between maintaining an open research culture that's really premised on collaboration and transparency, data sharing, et cetera. Mm-hmm.<affirmative>, um, with, you know, mitigating research integrity risks that are opposed by those seeking to misappropriate r and d to the detriment in national or economic security. So what this implementation guidance set forth and, and, you know, jumping ahead what to watch for is how the grant making agencies, you know, adopts their version of it through their own program requirements. Um, it, it had five areas of focus, um, notably, uh, seeking to streamline or standardize disclosure requirements for, um, disclosures that would assess conflicts of interest and conflicts of the commitment. This would be trying to, you know, make sure we know if investigators have, um, foreign affiliations, other support, uh, for their, uh, n NIH or other federally funded research that's, you know, coming from, um, internationally. Um, and I'll, I'll mention here, just at the end of August last year, the, the National Science and Technology Council Subcommittee on Research Security, which I know is a mouthful, but that's the<laugh>, the council that's spearheading this, um, announced draft standardization data fields and instructions for these types of disclosures. And they invited public comment, which closed at the end of October. So I think that, you know, we can expect more, um, development and progress on that front. Um, I'll just briefly mention some of the other elements of the implementation guidance and then what I think are sort of the takeaways or what to watch. But there's, um, you know, treatment of, uh, uh, a desire to universally adopt and harmonize, um, the use of researcher digital persistent identifiers. Mm-hmm. And that's to aid in sharing and reporting, um, it through digital research administrative systems. On this front, this is a practical matter. Um, n NIH already requires principal investigators to be registered with the orchid. Um, and at the end of, uh, just this past month, January of 23, it looked like NSF was moving in that direction as well. Um, I think most notably from the implementation guidance was the, um, inclusion of, of section on consequences for violation of disclosure requirements. And this really, um, you know, inclusion of this section may signal a shift in the enforcement priorities, um, from, you know, what is historically focused on individual investigators and whether they've under-reported their, their foreign affiliations, their other support, um, and really to more of a focus on scrutinizing institutional controls. But I'll, while I say that I, I know the factors cited is relevant to, you know, assessing institutional liability for non-compliance, we're still, you know, set a pretty high bar, for example, whether the organization failed to make its research community aware of disclosure requirements period, um, or whether it knew indivi, if it knew of an individual's failure to disclose and didn't remedy that prior to the grant application or other, you know, certification. Um, so this, and also the, the implementation guidance is discussion of research security program expectations are prompting institutions to take steps now, um, to educate leadership on the priority of investing in compliance in this space. Um, some are considering conducting updated security assessments, you know, and that could be holistic as part of, uh, for example, where these AMCs are embedded in healthcare providers, you know, routine, um, assessments you're doing for HIPAA purposes anyway. Um, and then also preparing for training their research communities and particularly their investigators on the, um, disclosure requirements. Um, so those are, you know, again, just some, some of the specifics, but really what to watch for, and institutions can tailor this based on the, um, you know, predominance of their federally funded portfolio, whether it's n nih, n s, nsf, d o d, you name it. Um, figure out and be on the lookout for, um, how the, how these requirements are translated into those specific grant making agencies program, um, guidance.
Speaker 2:Yeah. And I, I, I think to me that's the of, of, of all of the things that you've talked about, you know, that's from an institution standpoint, one of the things that stuck out is that if, if this is heading down the pike, it's something that, that everybody needs to back to the sort of get your house in order. It's a good time to, to, to, to do a check and see if, if in fact, you, you, you have all the things in place that you mentioned. So I think that hits on, on most everything that was, was in your article and, and that you and I had Had talked about. I don't, I don't think we have any other letters or numbers to cover<laugh>, so, um, but I, I do wanna, you know, thank you Rebecca. Um, you know, this has been great for, for, for me as well as to just, um, be able to, to learn a little bit more about what's happening 2023 and really do look forward to following some of this into, into 2024. So wanna just leave it, turn it over over to you for any final comments and then we, we can, we can close out and end, end the series.
Speaker 3:Yeah, no, that sounds great. And thank you, Tanya, for leading the discussion today, and it's really great, um, to talk with you. So I think, you know, my concluding remark would just be, there's, there's gifts and gets in these developments, right? Um, gives in terms of new, um, gives on the part of research institutions. That's the perspective I'm speaking from in terms of revised or new regulatory obligations, right? Those are gonna be, um, burdens or just, you know, compliance considerations to contend with, but gets in terms of new funding opportunities, whether that's through ARPA H or you know, what comes of the moonshot initiative. And so, you know, um, both burden and opportunity and give and gets. Um, but we'll continue to watch. And so thanks again for, for, um, the opportunity to talk with you today.
Speaker 1:Thank you for listening. If you enjoy this episode, be sure to subscribe to a H L A speaking of health law wherever you get your podcasts. To learn more about a H L A and the educational resources available to the health law community, visit American health law.org.