This episode of Vital Viewpoints on Healthcare unpacks the rapidly evolving regulatory landscape for pharmaceuticals. The discussion covers the challenges to innovation, such as the growing unpredictability in FDA policy, the challenges with reimbursement, and the increasing role of real-world evidence in bringing therapies to market. Julie Tierney, principal at Leavitt Partners (an 红领巾瓜报 Company) shares her expert perspectives on rare disease innovation and upcoming user fee negotiations; while Ben Shand, vice president at 红领巾瓜报, talks about why organizations must actively engage to navigate risk, identify opportunity, and ultimately improve patient access to care.
锘緽en Shand
Given all the unpredictability, I think it's a time for innovators to be engaged in the policy discussions. This is not a time to be sitting on the sidelines.
Jennifer Colamonico
You're listening to Vital Viewpoints on Healthcare. Let's get started. Today, I'm joined by two colleagues from our life sciences practice who are working at the intersection of government regulation, evidence and market strategy. Ben Shand is the vice president of client partnerships at HMRC, and he brings more than 15 years of experience advising biopharma, medtech and public sector organizations on policy, evidence generation, market access and regulatory strategy, helping leaders translate complex market dynamics into durable impact.
Julie Tierney is a principal at Leavitt Partners, which is an HMO company, and she has more than 25 years of experience in FDA law and policy, including senior leadership roles at the US Food and Drug Administration, where she served as chief of staff and is deputy director of the center for Biologics Evaluation and Research, where she helped shape major reforms such as the 21st century Cures Act.
We will examine how evolving regulatory frameworks and policy priorities are influencing innovation, commercialization and access across health care. And so thanks for being with us today. So, Julie, let me start with you. You've had a long career at FDA, impressive career working at the Center of Policy and Operations for more than two decades. You were chief of staff to the commissioner.
You've been involved in a lot of major changes that have happened over the years. So when you look at today's regulatory landscape, what feels most different from when you first joined the agency?
Julie Tierney
Thanks for that question. I think that it really is a shifting, shifting landscape in a lot of ways. And one of those is how, how FDA is making, making policy these days, for different and unexpected ways of making and announcing policies throughout my career. I think certainly predictable the direction FDA was going in. There are formal mechanisms such as regulation, regulations, notice and comment guidances, with, with some communication strategies sprinkled in occasionally I'd, I'd have a boss that I wish would not announce major initiatives from, from the podium before we had the guidance completely cut.
But now we're seeing, policy announcements, the journal articles, or posting on Lafayette's website or podcasts where it's really you have to do a lot of, tea leaf reading to figure out where the agency is heading. And it can take folks by surprise, if they're not paying close attention. I think it also represents an opportunity for those who are, paying attention and sort of steeped in what the FDA standard is to begin with so they can understand what is actually an impactful development versus something that is just reiterating what FDA is already doing and packaging it differently.
Jennifer Colamonico
That presents challenges, right? For clients seeking approval to understand the process. Ben, let me ask you, what do you see as the biggest challenge that pharma and biotech innovators face today, kind of in this environment, given all changes and agencies and obviously some recent high profile decisions? You know, do you think these stakeholders understand how to be successful today?
Ben Shand
Yeah. Picking one challenge there is tough. I think the sum it all up and what we hear from our clients most often is, the level of unpredictability. It's you know, for better or worse, in our health care system, what's happening inside and around the Beltway is really defining and shaping the market that innovators. Life sciences, biotech, pharma, that they're operating in.
And the decisions that FDA or CMS or, on the Hill, they've got both near-term and long term ramifications. So, you know, just thinking about the recent examples, two administrations in a row that the, a major policy, decisions or but, laws that affect the, the drug pricing and the long term impact of drug drug pricing.
And, you know, I think that that creates major problems for long term planning, both from a pipeline decision standpoint, forecasting, where to place bets and investments. And that's challenging when you know, the rules of the road just get, kind of changed, on a whim or by podcast or by, you know, journals, as Julie just alluded to.
So, I do think it's an exciting time, though, with the underlying, science, there's great opportunity for, for more innovation. But I think having a level of, stability, and a lack of unpredictability, would go a long way to supporting our clients.
Jennifer Colamonico
So many people maybe don't understand just how long it takes to bring a product to market. Right. So once you're at the 11th hour, like, what, 7 or 8, ten years since that, some of those decisions were made. Right? So these pricing or whatever decisions are happening at the end of what's a very long kind of approval journey.
And it's hard to change all that at the last minute.
Ben Shand
Absolutely. I mean, you're looking at a 10 to 15 year, runway to develop a product and bring it through to the market.
Jennifer Colamonico
So one of the areas it seems that there's been a lot of innovation and recently is, is various rare diseases, which has been super exciting and promising. And I think we just we're, we're having this conversation in March. There was just some focus on that. Julie, the the rare, the FDA rare disease innovation hub, was a significant moment.
I know you had a lot to do with that. Can you talk about kind of the the gaps? You know, what it was designed to address and, and sort of how, stakeholders should be engaging with it today.
Julie Tierney
Yeah, thanks. Really proud of the work that we did to set up set up the hub. And I think I was very fortunate to have perspective both from the commissioner's office. So seeing across the entire agency, as well as sort of the nuts and bolts, of, an individual center and how it worked. And for me, it was really important as I thought about, the ultimate goal of all this is to help patients.
You know, they don't know the difference between the center for biologics and the center for drugs. And so there shouldn't be really a difference in how they're engaging. There is certainly I think as much as you can should be an alignment between the standards depots and centers or, or applying in terms of what they're requiring. And I think, we did a lot of work internally to make sure that we were aligned across the centers.
There were some, some differences of opinions and advice that we're giving to developers. And I think there was a perception of a lack of alignment. And, you know, perception can really affect reality, especially in this space, rare diseases. It's got multiple challenges in terms of developing, you know, very small patient populations, possibility of not being able to randomized placebo.
You know, very steep manufacturing costs, for some of some of the very novel biologics, on the reimbursement pathways, all of those things sort of stack the odds against, getting the therapies across the finish line. But I think for the the rare Disease innovation hub, there was two things bringing together both of the centers, to talk about these sort of really meaty issues, very small patient populations or thinking about what the next generation of therapies look like for, for rare diseases that already had some therapies in place.
And then, the sort of the secondary thing was to have one place that the rare disease community could come to you at FDA. So not this mailbox or this person or that person and, and a particular center. But knowing that could come to this one hub and that it would get routed to the correct person at the agency and not just routed in terms of like, thanks, that's that's great.
Appreciate your perspective, but really incorporated into how FDA was doing its its regulatory work and how and sort of, sort of a feedback loop, and a more of a dialog that isn't that sort of a passive listening, device, I think, you know, to very small staff on loan for both centers. I would like one designated lead and like maybe for staff, that's not a lot to to run a whole program.
And I think there's been conversations about how to fund it moving forward. But I think it's a really exciting opportunity for that sort of collaboration that's really working for patients.
Jennifer Colamonico
Now, did that help? Not only kind of the innovation bringing the drug to market and getting through trials, but what about sort of the post-market surveillance? I mean, obviously with rare disease populations, like you said, small populations, the monitoring. Yeah, it's a little bit different. Right. The whole process. So does that also support kind of through post-launch and and kind of post-marketing.
Julie Tierney
Yeah I think it can it can support that. Of course there's you know you push for alignment as much as you can. And then sometimes there are going to be differences depending on the type of modality in question. Right. So there's long term follow up for gene therapies that you might not have. Was sort of a traditional small molecule drug that you know more about or you're able to characterize, its short term, toxicity.
But, you know, I think looking at post-marketing safety, getting alignment on that as much as you can, or figuring out why you don't have the alignment, being able to explain it, that's, that's really important to, to folks as well. And then I think, you know, how we apply how FDA acquires the accelerated approval pathway, which has a huge component of, you know, it's approval based on a biomarker or an intermediate clinical endpoint.
And then there's a component of accelerated approval in the post-market, where you really are looking at the clinical benefit of the product and, work through the hub, as well as the Accelerated Approval Coordinating Council at FDA to try to make sure there was as much alignment and consistent practices as possible across the centers.
Jennifer Colamonico
So I'm just thinking about the pricing conversation. You know, some of that is, is, these drugs hold promise, of course, to improve outcomes in some cases cure, of course. But, you know, the the ability to measure that, I think is increasingly a factor in the pricing discussions. So we know that the FDA approval is only kind of one part of the journey.
Of these therapies. What do you see? You know, connecting the regulatory side to the market side, what is the greatest disconnect between regulatory success and then reimbursement.
Ben Shand
At the crux of the disconnect, is that FCA and CMS payers, you know, they're evaluating evidence through different frameworks and really for, for different purposes, and different timelines in mind. You know, is a product safe and effective relative to its claims versus, you know, is it reasonable and necessary to cover, and pay for, for this treatment?
So, that's, you know, an issue that that will take a lot to be ultimately resolved. And the payers are typically operating on a calendar year budget cycle and managing risk and spend accordingly. So, when they're trying to understand durability of response over a longer time horizon, like that's a, that's a big, that's a big challenge.
And maybe one where, where policy solutions can absolve that. I do think, though, there's no reason to be optimistic, around the use of real world evidence. You know, FDA accepts real world evidence. There's a long track record on the med device side, on the oncology side as well. We've seen, you know, the submission of that, FDA just announced the plausible mechanism framework and would love to get, you know, do his take on that.
But, you know, to me, it seems like, there is an elevated role for real world evidence, within that that framework when clinical trials on feasible whether that's, you know, natural history studies, were being able to you know, from a payer standpoint, you know, you're, you're thinking about the evidence that you're generating for FDA, but then also have a longer view of that for the for the payer later on down the line to show clinical outcomes, durability, perhaps even budget impact over, over a longer time.
So, you know, I think in this kind of gets to the part of the prior question on what what clients are doing to be successful that I didn't maybe totally answer, but, thinking holistically about products as, as, you know, developing them in R&D, but then thinking about the how to to present that to the agency. But you've got to be thinking about longer term on, on the payer expectations from an evidence, standpoint.
And then secondly, given all the, unpredictability, I think it's a time for, for, innovators to be engaged in the policy discussions, whether that's directly, with, with regulators or with their, customers and other stakeholders and patient advocacy groups as well. And this is not a time to be sitting on the sidelines.
I think it's a time to be engaged. And we do, you know, work with our clients, to help them do that strategically.
Julie Tierney
I totally agree with all of what Dan said. I think, with sort of new frameworks, like the plausible mechanism framework, which is about, you know, a pathway to bring individualized, therapies to, to market and then allow for them to have changes in the post-market. So you think of it sort of as a, these are very, very small, you know, and of one and a few, I think is what is the term that we use, where you might have to, take as a backbone of a product and change it slightly to a different genetic mutation, others.
And, and then sort of a sponsor could come in with data in several different mutations, that where the product uses the same backbone, sort of as a platform, that approval. And then where there's a plausible mechanism of how it is interacting with the pathways, or if the, you know, the genetic pathway or the production of proteins or things like that, FDA would allow in the post-market additional changes for, for additional mutations.
So that sort of flexibility. But, but I think, you know what, what FDA leadership is signaling with the use of the expanded use of real world evidence, which has been, pretty extensively used in the in the device space or more extensively used in the device space. Wanting to use it, use it more, in the drugs and biologic space.
And that's been part of work that's happened since 21st century cures with multiple user fee reauthorization, sort of. FDA has been tasked with coming up with a framework for real world evidence, used to offer what evidence? In advance for biologics patients, drug development, those sorts of frameworks to help provide more, patient input or, opportunities for flexibility in this sense forward, that's going to rely on additional evidence generation in the post-market.
Jennifer Colamonico
Really interesting. So we're coming upon the next round of user fees, right. With the, in 2027. So, you know, given your background there, what do you what are you watching? What policies and proposals do you think are likely to evolve in this next year as we head into this next round of user fees, you know, particularly in rare disease development.
But, you know, be curious kind of anywhere what you're what your senses of what we might see there.
Julie Tierney
So the way that this, usually happens is every five years, the user fees are reauthorized. And as you mentioned, there drop in September of 27, which seems like it's far away. But it's actually not. And usually what happens is about two years previous to that, FDA and the treats, get together and negotiate commitments around processes and sort of regulatory science deliverables, that that FDA, delivers on and in return for, for fees that, that fund the staffing of the agency.
That commitment letter, gets endorsed by their ratifies and then goes up the chain, through the white House and is transmitted to Congress. And so I think they're a close term to wrapping up, the negotiations around the commitment letter. That's my expectation. There's probably some wild cards in there in terms of navigating the clearance process.
Secretary has said that he is, not supportive. In 2017, when, during the first Trump administration, I was another reauthorization, in the white House, we sort of held our breath a little bit because we thought maybe, they might want to try to get a better deal. But ultimately, that was reauthorized in, in 2017.
So hoping that, is transmitted and then, Congress will, will codify those, some of those commitments and authorize FDA to collect the user fees. But then, we'll probably throw on policies like we think about it's like ornaments on the Christmas tree. And, you know, we were talking earlier about it takes a long time to develop, drugs and biologics, right?
This is not a six month endeavor is a multiyear I like there are different policy levers that we can probably use to reduce the length of time that it takes, but we're talking about a multi-year, multimillion dollar, endeavor. And I think because of that, as we're looking at sort of these changes and policies, particular might look like it's a streamlining, really an opportunity.
I think it's important to, to seize on those opportunities, but also think about their durability. And so in 3 or 4 years is something that's announced on the website going to be binding on a subsequent FDA? If it's the if it's lowers the bar, you know, I just I'm not sure. So so I think that's going to be on everyone's mind predictability durability of these policies.
So I would anticipate there's probably going to be, FDA policy reforms about streamlining clinical trial start ups. First in human studies, because that is some place that we're seeing, a lot of competition with other global, with other countries, China and Australia, among others, with with early clinical trials moving over there. And there's some probably some FDA policy reforms that can help to, to locate the start of trials in the United States.
So I think we're probably going to see that. I think we're also with this focus on rare diseases and sort of the volatility that we've been seeing. We're likely to see some legislation establishing new pathways. Even if it's something that FDA could do on its own, Congress often will codify new pathways that what they did with accelerated approval, breakthrough therapy, live in a population of adults, pathway.
You know, it sort of gives, the congressional or provider to FDA to say, like, hey, we as a society have decided FDA, this is how you should balance. Balance, that it fits and risks of products. And I also think that it gives some, some durability, to, to the policies as well. It says, okay, we're going to accept one clinical trial as, as our default.
The other element to that is sort of some processes around early advice. Perhaps how FDA can be more transparent about it or, make sure that that companies can rely on that early advice that they got through their development process. And then also maybe that, that Congress, asks FDA to help to develop these frameworks to do, what they've done in the past with, you know, workshops and guidance documents that that explain, you know, FDA's current thinking there may be deliverables in the statute around around that as well.
So not, specific requirements of what has to be included, but, specific topics that need to be addressed. And then FDA needs to hold a public meeting, right? A write a guidance, write a white paper, take comments, revise that, that sort of what has happened in the past. And I anticipate that would be layered on top of that.
It changes.
Jennifer Colamonico
So just to be clear, the congressional action with that will take place in 2026, or whether that be 2027.
Julie Tierney
So that'll start to I think there's already socialization happening right now around policy ideas. Senator Cassidy, issued a white paper on FDA modernization ideas. There's other offices that are already thinking about ideas and conversations that are happening. Those would probably be introduced in the beginning of, of the new Congress. In 27.
Ben Shand
We mentioned the alternative forms of where policy is being communicated. And if you've listened to the Commissioner McCarry speak, it sounds a little rosier for industry and for innovators. You know how he talks about innovating, whether or modernizing, FDA. But, you know, I think from, from our clients, we've heard that maybe that that picture on leveraging AI in other ways or making operational strengths.
And I think that that that seems a little bit, in conflict with, with how our clients maybe are engaged with the agency right now or what we're hearing out of people at the agency. Which certainly adds on to this unpredictability. But I'm curious, you know, you know, Julian, your take on kind of seeing through what's being communicated in the commissioner on all sorts of mediums, versus, you know, what's actually practical from a modernization standpoint at FDA?
Julie Tierney
What are one of the things that I, get a lot of work on when I was at FDA is making sure that we have organizational changes that could, that could support, scientific, and regulatory changes. So, for instance, when I was in the center for biologics, one of the efforts that we undertook as selling gene therapy was sort of exploding was saying, we don't just need to hire new staff.
It's not just enough to have more people. We need to have, different layers of leadership to help ensure consistency and provide guidance to, to younger staff. I think, FDA right now is sort of in an uphill battle, continuing to lose staff. And it's pretty hard to, to recruit, in this environment. It's not, federal service.
It's not the, the profession that it once, once was with the security that at once once had, which is, which is sad. But, I'm hoping that they'll be able to to right the ship. There is a hiring initiative underway. So, so hopefully they'll bring on not just more people, but the right people. They've got some experience and wisdom and can help, help guide things are moving forward.
But certainly, it's not just about the, the, you know, flat numbers of, of drugs or biologics that are approved. Because if you look over that, the those trends are, you know, within the bounds of, of normalcy. But what we're hearing from our clients about changes in advice about, meeting, deadlines that that that at Mr..
Our meetings that are convert converted into written response only rather than being able to meet with that agency to engage a little more fully. I think definitely is a different direction that the agency has been had it. And that's where I think some of these I'm, I'm hopeful that the commitment letter, with industry will help on that, but also where I, where I see Congress probably stepping up and and putting in some belt suspenders, to help with the processes.
Jennifer Colamonico
So but then how, I mean, so that's a great place to pivot. Right? So predictability is the name of the game, but we know that we are in slightly unconventional times of a lot of these fronts for all sorts of reasons. The leadership innovation and technology. Ben, how are you guiding clients? I mean, in the, in these times, you know, not only in terms of their current product pipeline that is, you know, as we talked about, underway, but, you know, how they're innovating for the future, in times like these.
Ben Shand
So clients come to me and come to it because of our expertise, because we've sat in the seats where decisions get made, whether that be at FDA, whether it be at CMS, whether that be with with payers or, health administrators at the operational level. Ultimately, we feel it's important to help our clients understand the impact of a regulatory change or a policy change, whether that be from a quantitative standpoint or, an opportunity standpoint on how to engage on that.
Julie Tierney
In these unconventional times of policy coming from so many different directions and, you know, changes in leadership and staff, back in the administration, at the agencies as well as in Congress, I think it's really important to have advisors that not only have sat in these seats and understand the technical, the technical jargon, but and can translate that into to real world, plain language, but also have a more ecosystem awareness.
So not only can, plug in on some of the technical advice, but also help clients identify when these new policies or changes, present opportunities, as well as identify the risks before they become full blown risks to help clients stay ahead of the game.
Jennifer Colamonico
So the value of having people who have had real, this real life experience in these seats is they can, you know, guide not not just panic, not just react, but, you know, read the tea leaves right kind of guide guide you through, disconnect. What you're seeing in the headlines may not be really what's happening on the ground.
So that kind of it's almost like a translation.
Julie Tierney
A translation of what you see in the headlines, what that really means. But from people who sort of know the systems that are at work, but also some of the, the technical, back and forth with the agency is, certainly there are folks that can provide advice on how to power study and, how to design a control arm or do some of the manufacturing work.
But I think, having people like me who's engaged in those conversations and are able to talk that talk, and at the same time, combine that with the awareness of sort of what's happening beyond just the technical responses to the agency and where that could present an opportunity, like, you know, where where it's going to be more risky, but it might not have become a full fledged risk yet.
Right?
Jennifer Colamonico
Well, the risk modeling is a good point, right? So you can take that and dump that into then models. Right. And say, all right, here are these different scenarios. Then let's try to put some predictability into unpredictable situations right through modeling.
Ben Shand
Understanding the quantitative impact of one of these changes is certainly important. But further to that, what you know, what is it? What do our clients do about that? What is their strategy in terms of the bringing a product to the market? They know they need to generate evidence along the way. They know they need to engage with FDA.
And then eventually they'll be, you know, looking for coverage and reimbursement. There are important strategies along the way that we support our clients with, and we think it's important to have a that holistic view. Across every decision point, from when a, when a product is, you know, reaching the milestone of approval all the way through to, to reaching the ultimately the patient.
Jennifer Colamonico
Yeah, it's all it's almost like game theory upon game theory. Right? You're going to have your, your modeling at the early stages, but then being able to come back in, like you said, at each kind of stage was a reassess. Right. Which direction we're going. And then you can account for these sort of unpredictable and yet, you know, predictable changes.
If you're reading the tea leaves correctly.
So let me just ask you, it's a it's sort of a favorite question on our, on our podcast because, you know, when we speak to people who understand their, their markets and their industries and their, you know, their policy areas with such depth, you know, there's sometimes changes that could improve things that, that most people don't know about.
So I would ask you both, if you if you had a magic wand, and you could change one element, you know, Julie, perhaps for you, you know, in the rare disease kind of ecosystem or urban in the, in the, you know, approval and pricing system. I mean, if there's like one thing that you could change, how would you wield that magic wand.
Julie Tierney
If we could decrease in a, in a scientifically rigorous way and, you know, legal and, regulatory really stable away, decrease reliance on clinical trial. So focus on, on information outside of clinical trials. When we're at this sort of amazing point in, science and technology, we've got, you know, genome editing happening, we've got AI and all of these tools at our disposal.
If there's a way, that we could take what we know about what we know about molecules, what we know about pathways, there's so much that we don't know. But, how the pre-clinical space could utilize that new technology to be more predictive of what drugs are going to work and when, and then how data outside of clinical trials could be leveraged so that we're not, you know, still stuck in, you know, two randomized clinical trials or one plus confirmatory evidence.
If we could figure out a way that we are less reliant on doing experiments in humans, to prove whether or not a drug works. I think that would be amazing.
Jennifer Colamonico
And what about for you? How would you wield your magic wand?
Ben Shand
Magic wand? I've got three little kids, so I'd like to say I'm experienced with magic wands. And I would take a a big swing with this one. Perhaps a little a little broader than the maybe initially asked me. But, you know, as we, we spend too much money on health care in the US and it's unsustainable. And it's created a policy environment where we've had downward pressure on, on spend, on budgets and, you know, ultimately, it's my belief that the spend is driven by the incentives across, our care continuum.
And so with my wand, I would, help to realign and kind of modernize the incentives. And, you know, we want to incentivize towards the outcomes that we want. And the outcome is ultimately a healthier America. And I think that from, an innovation standpoint, we want to be incentivizing great foundational root cause research, great translational research, to bring that innovation to the risk takers who are going to bring it along.
Ultimately, that risk needs to be utilized. And in return on investment there. So we need that to be functioning and working to keep innovation flowing through our system. And, you know, could go on and on about incentives, for, across the care continuum towards the patient, but ultimately having the right to modernized incentives, I think, goes a long way towards achieving outcomes that we're looking for.
Jennifer Colamonico
Good one, not one I would have expected in this conversation, but always a good one. I think, the misalignment of incentives sort of it's amazing how many of these conversations that's relevant, to no matter what part of health care we're discussing and certainly relevant to innovation in therapies and treatments. So I appreciate that. Well, this is a big thorny topic, and I think you both have added some, interesting dimensions here.
So really appreciate your time. And certainly a conversation will continue to have and we'll be watching this space very carefully this year particularly, you know, as Congress takes up these issues and, seeing how they, how they use their magic wand, so to speak, to, to guide through those, they're, you know, they're the new user fees and what that will portend for, for FDA moving forward.
So appreciate both your time. Thank you so much.
For this episode of Vital Viewpoints on Health Care is sponsored by 红领巾瓜报 Information Services. 红领巾瓜报IS is a subscription based service that provides state level data on publicly sponsored programs like Medicaid from the latest managed care enrollment, market share, and financial performance data to up to date RFP calendars and state by state overviews, 红领巾瓜报IS has all the information you'll need to power your initiatives to success.
This podcast was produced by myself, Jennifer Colamonico along with Tiffany McKenzie in collaboration with our guests. The content is the property of 红领巾瓜报.
Given all the unpredictability, I think it's a time for innovators to be engaged in the policy discussions. This is not a time to be sitting on the sidelines.
Jennifer Colamonico
You're listening to Vital Viewpoints on Healthcare. Let's get started. Today, I'm joined by two colleagues from our life sciences practice who are working at the intersection of government regulation, evidence and market strategy. Ben Shand is the vice president of client partnerships at HMRC, and he brings more than 15 years of experience advising biopharma, medtech and public sector organizations on policy, evidence generation, market access and regulatory strategy, helping leaders translate complex market dynamics into durable impact.
Julie Tierney is a principal at Leavitt Partners, which is an HMO company, and she has more than 25 years of experience in FDA law and policy, including senior leadership roles at the US Food and Drug Administration, where she served as chief of staff and is deputy director of the center for Biologics Evaluation and Research, where she helped shape major reforms such as the 21st century Cures Act.
We will examine how evolving regulatory frameworks and policy priorities are influencing innovation, commercialization and access across health care. And so thanks for being with us today. So, Julie, let me start with you. You've had a long career at FDA, impressive career working at the Center of Policy and Operations for more than two decades. You were chief of staff to the commissioner.
You've been involved in a lot of major changes that have happened over the years. So when you look at today's regulatory landscape, what feels most different from when you first joined the agency?
Julie Tierney
Thanks for that question. I think that it really is a shifting, shifting landscape in a lot of ways. And one of those is how, how FDA is making, making policy these days, for different and unexpected ways of making and announcing policies throughout my career. I think certainly predictable the direction FDA was going in. There are formal mechanisms such as regulation, regulations, notice and comment guidances, with, with some communication strategies sprinkled in occasionally I'd, I'd have a boss that I wish would not announce major initiatives from, from the podium before we had the guidance completely cut.
But now we're seeing, policy announcements, the journal articles, or posting on Lafayette's website or podcasts where it's really you have to do a lot of, tea leaf reading to figure out where the agency is heading. And it can take folks by surprise, if they're not paying close attention. I think it also represents an opportunity for those who are, paying attention and sort of steeped in what the FDA standard is to begin with so they can understand what is actually an impactful development versus something that is just reiterating what FDA is already doing and packaging it differently.
Jennifer Colamonico
That presents challenges, right? For clients seeking approval to understand the process. Ben, let me ask you, what do you see as the biggest challenge that pharma and biotech innovators face today, kind of in this environment, given all changes and agencies and obviously some recent high profile decisions? You know, do you think these stakeholders understand how to be successful today?
Ben Shand
Yeah. Picking one challenge there is tough. I think the sum it all up and what we hear from our clients most often is, the level of unpredictability. It's you know, for better or worse, in our health care system, what's happening inside and around the Beltway is really defining and shaping the market that innovators. Life sciences, biotech, pharma, that they're operating in.
And the decisions that FDA or CMS or, on the Hill, they've got both near-term and long term ramifications. So, you know, just thinking about the recent examples, two administrations in a row that the, a major policy, decisions or but, laws that affect the, the drug pricing and the long term impact of drug drug pricing.
And, you know, I think that that creates major problems for long term planning, both from a pipeline decision standpoint, forecasting, where to place bets and investments. And that's challenging when you know, the rules of the road just get, kind of changed, on a whim or by podcast or by, you know, journals, as Julie just alluded to.
So, I do think it's an exciting time, though, with the underlying, science, there's great opportunity for, for more innovation. But I think having a level of, stability, and a lack of unpredictability, would go a long way to supporting our clients.
Jennifer Colamonico
So many people maybe don't understand just how long it takes to bring a product to market. Right. So once you're at the 11th hour, like, what, 7 or 8, ten years since that, some of those decisions were made. Right? So these pricing or whatever decisions are happening at the end of what's a very long kind of approval journey.
And it's hard to change all that at the last minute.
Ben Shand
Absolutely. I mean, you're looking at a 10 to 15 year, runway to develop a product and bring it through to the market.
Jennifer Colamonico
So one of the areas it seems that there's been a lot of innovation and recently is, is various rare diseases, which has been super exciting and promising. And I think we just we're, we're having this conversation in March. There was just some focus on that. Julie, the the rare, the FDA rare disease innovation hub, was a significant moment.
I know you had a lot to do with that. Can you talk about kind of the the gaps? You know, what it was designed to address and, and sort of how, stakeholders should be engaging with it today.
Julie Tierney
Yeah, thanks. Really proud of the work that we did to set up set up the hub. And I think I was very fortunate to have perspective both from the commissioner's office. So seeing across the entire agency, as well as sort of the nuts and bolts, of, an individual center and how it worked. And for me, it was really important as I thought about, the ultimate goal of all this is to help patients.
You know, they don't know the difference between the center for biologics and the center for drugs. And so there shouldn't be really a difference in how they're engaging. There is certainly I think as much as you can should be an alignment between the standards depots and centers or, or applying in terms of what they're requiring. And I think, we did a lot of work internally to make sure that we were aligned across the centers.
There were some, some differences of opinions and advice that we're giving to developers. And I think there was a perception of a lack of alignment. And, you know, perception can really affect reality, especially in this space, rare diseases. It's got multiple challenges in terms of developing, you know, very small patient populations, possibility of not being able to randomized placebo.
You know, very steep manufacturing costs, for some of some of the very novel biologics, on the reimbursement pathways, all of those things sort of stack the odds against, getting the therapies across the finish line. But I think for the the rare Disease innovation hub, there was two things bringing together both of the centers, to talk about these sort of really meaty issues, very small patient populations or thinking about what the next generation of therapies look like for, for rare diseases that already had some therapies in place.
And then, the sort of the secondary thing was to have one place that the rare disease community could come to you at FDA. So not this mailbox or this person or that person and, and a particular center. But knowing that could come to this one hub and that it would get routed to the correct person at the agency and not just routed in terms of like, thanks, that's that's great.
Appreciate your perspective, but really incorporated into how FDA was doing its its regulatory work and how and sort of, sort of a feedback loop, and a more of a dialog that isn't that sort of a passive listening, device, I think, you know, to very small staff on loan for both centers. I would like one designated lead and like maybe for staff, that's not a lot to to run a whole program.
And I think there's been conversations about how to fund it moving forward. But I think it's a really exciting opportunity for that sort of collaboration that's really working for patients.
Jennifer Colamonico
Now, did that help? Not only kind of the innovation bringing the drug to market and getting through trials, but what about sort of the post-market surveillance? I mean, obviously with rare disease populations, like you said, small populations, the monitoring. Yeah, it's a little bit different. Right. The whole process. So does that also support kind of through post-launch and and kind of post-marketing.
Julie Tierney
Yeah I think it can it can support that. Of course there's you know you push for alignment as much as you can. And then sometimes there are going to be differences depending on the type of modality in question. Right. So there's long term follow up for gene therapies that you might not have. Was sort of a traditional small molecule drug that you know more about or you're able to characterize, its short term, toxicity.
But, you know, I think looking at post-marketing safety, getting alignment on that as much as you can, or figuring out why you don't have the alignment, being able to explain it, that's, that's really important to, to folks as well. And then I think, you know, how we apply how FDA acquires the accelerated approval pathway, which has a huge component of, you know, it's approval based on a biomarker or an intermediate clinical endpoint.
And then there's a component of accelerated approval in the post-market, where you really are looking at the clinical benefit of the product and, work through the hub, as well as the Accelerated Approval Coordinating Council at FDA to try to make sure there was as much alignment and consistent practices as possible across the centers.
Jennifer Colamonico
So I'm just thinking about the pricing conversation. You know, some of that is, is, these drugs hold promise, of course, to improve outcomes in some cases cure, of course. But, you know, the the ability to measure that, I think is increasingly a factor in the pricing discussions. So we know that the FDA approval is only kind of one part of the journey.
Of these therapies. What do you see? You know, connecting the regulatory side to the market side, what is the greatest disconnect between regulatory success and then reimbursement.
Ben Shand
At the crux of the disconnect, is that FCA and CMS payers, you know, they're evaluating evidence through different frameworks and really for, for different purposes, and different timelines in mind. You know, is a product safe and effective relative to its claims versus, you know, is it reasonable and necessary to cover, and pay for, for this treatment?
So, that's, you know, an issue that that will take a lot to be ultimately resolved. And the payers are typically operating on a calendar year budget cycle and managing risk and spend accordingly. So, when they're trying to understand durability of response over a longer time horizon, like that's a, that's a big, that's a big challenge.
And maybe one where, where policy solutions can absolve that. I do think, though, there's no reason to be optimistic, around the use of real world evidence. You know, FDA accepts real world evidence. There's a long track record on the med device side, on the oncology side as well. We've seen, you know, the submission of that, FDA just announced the plausible mechanism framework and would love to get, you know, do his take on that.
But, you know, to me, it seems like, there is an elevated role for real world evidence, within that that framework when clinical trials on feasible whether that's, you know, natural history studies, were being able to you know, from a payer standpoint, you know, you're, you're thinking about the evidence that you're generating for FDA, but then also have a longer view of that for the for the payer later on down the line to show clinical outcomes, durability, perhaps even budget impact over, over a longer time.
So, you know, I think in this kind of gets to the part of the prior question on what what clients are doing to be successful that I didn't maybe totally answer, but, thinking holistically about products as, as, you know, developing them in R&D, but then thinking about the how to to present that to the agency. But you've got to be thinking about longer term on, on the payer expectations from an evidence, standpoint.
And then secondly, given all the, unpredictability, I think it's a time for, for, innovators to be engaged in the policy discussions, whether that's directly, with, with regulators or with their, customers and other stakeholders and patient advocacy groups as well. And this is not a time to be sitting on the sidelines.
I think it's a time to be engaged. And we do, you know, work with our clients, to help them do that strategically.
Julie Tierney
I totally agree with all of what Dan said. I think, with sort of new frameworks, like the plausible mechanism framework, which is about, you know, a pathway to bring individualized, therapies to, to market and then allow for them to have changes in the post-market. So you think of it sort of as a, these are very, very small, you know, and of one and a few, I think is what is the term that we use, where you might have to, take as a backbone of a product and change it slightly to a different genetic mutation, others.
And, and then sort of a sponsor could come in with data in several different mutations, that where the product uses the same backbone, sort of as a platform, that approval. And then where there's a plausible mechanism of how it is interacting with the pathways, or if the, you know, the genetic pathway or the production of proteins or things like that, FDA would allow in the post-market additional changes for, for additional mutations.
So that sort of flexibility. But, but I think, you know what, what FDA leadership is signaling with the use of the expanded use of real world evidence, which has been, pretty extensively used in the in the device space or more extensively used in the device space. Wanting to use it, use it more, in the drugs and biologic space.
And that's been part of work that's happened since 21st century cures with multiple user fee reauthorization, sort of. FDA has been tasked with coming up with a framework for real world evidence, used to offer what evidence? In advance for biologics patients, drug development, those sorts of frameworks to help provide more, patient input or, opportunities for flexibility in this sense forward, that's going to rely on additional evidence generation in the post-market.
Jennifer Colamonico
Really interesting. So we're coming upon the next round of user fees, right. With the, in 2027. So, you know, given your background there, what do you what are you watching? What policies and proposals do you think are likely to evolve in this next year as we head into this next round of user fees, you know, particularly in rare disease development.
But, you know, be curious kind of anywhere what you're what your senses of what we might see there.
Julie Tierney
So the way that this, usually happens is every five years, the user fees are reauthorized. And as you mentioned, there drop in September of 27, which seems like it's far away. But it's actually not. And usually what happens is about two years previous to that, FDA and the treats, get together and negotiate commitments around processes and sort of regulatory science deliverables, that that FDA, delivers on and in return for, for fees that, that fund the staffing of the agency.
That commitment letter, gets endorsed by their ratifies and then goes up the chain, through the white House and is transmitted to Congress. And so I think they're a close term to wrapping up, the negotiations around the commitment letter. That's my expectation. There's probably some wild cards in there in terms of navigating the clearance process.
Secretary has said that he is, not supportive. In 2017, when, during the first Trump administration, I was another reauthorization, in the white House, we sort of held our breath a little bit because we thought maybe, they might want to try to get a better deal. But ultimately, that was reauthorized in, in 2017.
So hoping that, is transmitted and then, Congress will, will codify those, some of those commitments and authorize FDA to collect the user fees. But then, we'll probably throw on policies like we think about it's like ornaments on the Christmas tree. And, you know, we were talking earlier about it takes a long time to develop, drugs and biologics, right?
This is not a six month endeavor is a multiyear I like there are different policy levers that we can probably use to reduce the length of time that it takes, but we're talking about a multi-year, multimillion dollar, endeavor. And I think because of that, as we're looking at sort of these changes and policies, particular might look like it's a streamlining, really an opportunity.
I think it's important to, to seize on those opportunities, but also think about their durability. And so in 3 or 4 years is something that's announced on the website going to be binding on a subsequent FDA? If it's the if it's lowers the bar, you know, I just I'm not sure. So so I think that's going to be on everyone's mind predictability durability of these policies.
So I would anticipate there's probably going to be, FDA policy reforms about streamlining clinical trial start ups. First in human studies, because that is some place that we're seeing, a lot of competition with other global, with other countries, China and Australia, among others, with with early clinical trials moving over there. And there's some probably some FDA policy reforms that can help to, to locate the start of trials in the United States.
So I think we're probably going to see that. I think we're also with this focus on rare diseases and sort of the volatility that we've been seeing. We're likely to see some legislation establishing new pathways. Even if it's something that FDA could do on its own, Congress often will codify new pathways that what they did with accelerated approval, breakthrough therapy, live in a population of adults, pathway.
You know, it sort of gives, the congressional or provider to FDA to say, like, hey, we as a society have decided FDA, this is how you should balance. Balance, that it fits and risks of products. And I also think that it gives some, some durability, to, to the policies as well. It says, okay, we're going to accept one clinical trial as, as our default.
The other element to that is sort of some processes around early advice. Perhaps how FDA can be more transparent about it or, make sure that that companies can rely on that early advice that they got through their development process. And then also maybe that, that Congress, asks FDA to help to develop these frameworks to do, what they've done in the past with, you know, workshops and guidance documents that that explain, you know, FDA's current thinking there may be deliverables in the statute around around that as well.
So not, specific requirements of what has to be included, but, specific topics that need to be addressed. And then FDA needs to hold a public meeting, right? A write a guidance, write a white paper, take comments, revise that, that sort of what has happened in the past. And I anticipate that would be layered on top of that.
It changes.
Jennifer Colamonico
So just to be clear, the congressional action with that will take place in 2026, or whether that be 2027.
Julie Tierney
So that'll start to I think there's already socialization happening right now around policy ideas. Senator Cassidy, issued a white paper on FDA modernization ideas. There's other offices that are already thinking about ideas and conversations that are happening. Those would probably be introduced in the beginning of, of the new Congress. In 27.
Ben Shand
We mentioned the alternative forms of where policy is being communicated. And if you've listened to the Commissioner McCarry speak, it sounds a little rosier for industry and for innovators. You know how he talks about innovating, whether or modernizing, FDA. But, you know, I think from, from our clients, we've heard that maybe that that picture on leveraging AI in other ways or making operational strengths.
And I think that that that seems a little bit, in conflict with, with how our clients maybe are engaged with the agency right now or what we're hearing out of people at the agency. Which certainly adds on to this unpredictability. But I'm curious, you know, you know, Julian, your take on kind of seeing through what's being communicated in the commissioner on all sorts of mediums, versus, you know, what's actually practical from a modernization standpoint at FDA?
Julie Tierney
What are one of the things that I, get a lot of work on when I was at FDA is making sure that we have organizational changes that could, that could support, scientific, and regulatory changes. So, for instance, when I was in the center for biologics, one of the efforts that we undertook as selling gene therapy was sort of exploding was saying, we don't just need to hire new staff.
It's not just enough to have more people. We need to have, different layers of leadership to help ensure consistency and provide guidance to, to younger staff. I think, FDA right now is sort of in an uphill battle, continuing to lose staff. And it's pretty hard to, to recruit, in this environment. It's not, federal service.
It's not the, the profession that it once, once was with the security that at once once had, which is, which is sad. But, I'm hoping that they'll be able to to right the ship. There is a hiring initiative underway. So, so hopefully they'll bring on not just more people, but the right people. They've got some experience and wisdom and can help, help guide things are moving forward.
But certainly, it's not just about the, the, you know, flat numbers of, of drugs or biologics that are approved. Because if you look over that, the those trends are, you know, within the bounds of, of normalcy. But what we're hearing from our clients about changes in advice about, meeting, deadlines that that that at Mr..
Our meetings that are convert converted into written response only rather than being able to meet with that agency to engage a little more fully. I think definitely is a different direction that the agency has been had it. And that's where I think some of these I'm, I'm hopeful that the commitment letter, with industry will help on that, but also where I, where I see Congress probably stepping up and and putting in some belt suspenders, to help with the processes.
Jennifer Colamonico
So but then how, I mean, so that's a great place to pivot. Right? So predictability is the name of the game, but we know that we are in slightly unconventional times of a lot of these fronts for all sorts of reasons. The leadership innovation and technology. Ben, how are you guiding clients? I mean, in the, in these times, you know, not only in terms of their current product pipeline that is, you know, as we talked about, underway, but, you know, how they're innovating for the future, in times like these.
Ben Shand
So clients come to me and come to it because of our expertise, because we've sat in the seats where decisions get made, whether that be at FDA, whether it be at CMS, whether that be with with payers or, health administrators at the operational level. Ultimately, we feel it's important to help our clients understand the impact of a regulatory change or a policy change, whether that be from a quantitative standpoint or, an opportunity standpoint on how to engage on that.
Julie Tierney
In these unconventional times of policy coming from so many different directions and, you know, changes in leadership and staff, back in the administration, at the agencies as well as in Congress, I think it's really important to have advisors that not only have sat in these seats and understand the technical, the technical jargon, but and can translate that into to real world, plain language, but also have a more ecosystem awareness.
So not only can, plug in on some of the technical advice, but also help clients identify when these new policies or changes, present opportunities, as well as identify the risks before they become full blown risks to help clients stay ahead of the game.
Jennifer Colamonico
So the value of having people who have had real, this real life experience in these seats is they can, you know, guide not not just panic, not just react, but, you know, read the tea leaves right kind of guide guide you through, disconnect. What you're seeing in the headlines may not be really what's happening on the ground.
So that kind of it's almost like a translation.
Julie Tierney
A translation of what you see in the headlines, what that really means. But from people who sort of know the systems that are at work, but also some of the, the technical, back and forth with the agency is, certainly there are folks that can provide advice on how to power study and, how to design a control arm or do some of the manufacturing work.
But I think, having people like me who's engaged in those conversations and are able to talk that talk, and at the same time, combine that with the awareness of sort of what's happening beyond just the technical responses to the agency and where that could present an opportunity, like, you know, where where it's going to be more risky, but it might not have become a full fledged risk yet.
Right?
Jennifer Colamonico
Well, the risk modeling is a good point, right? So you can take that and dump that into then models. Right. And say, all right, here are these different scenarios. Then let's try to put some predictability into unpredictable situations right through modeling.
Ben Shand
Understanding the quantitative impact of one of these changes is certainly important. But further to that, what you know, what is it? What do our clients do about that? What is their strategy in terms of the bringing a product to the market? They know they need to generate evidence along the way. They know they need to engage with FDA.
And then eventually they'll be, you know, looking for coverage and reimbursement. There are important strategies along the way that we support our clients with, and we think it's important to have a that holistic view. Across every decision point, from when a, when a product is, you know, reaching the milestone of approval all the way through to, to reaching the ultimately the patient.
Jennifer Colamonico
Yeah, it's all it's almost like game theory upon game theory. Right? You're going to have your, your modeling at the early stages, but then being able to come back in, like you said, at each kind of stage was a reassess. Right. Which direction we're going. And then you can account for these sort of unpredictable and yet, you know, predictable changes.
If you're reading the tea leaves correctly.
So let me just ask you, it's a it's sort of a favorite question on our, on our podcast because, you know, when we speak to people who understand their, their markets and their industries and their, you know, their policy areas with such depth, you know, there's sometimes changes that could improve things that, that most people don't know about.
So I would ask you both, if you if you had a magic wand, and you could change one element, you know, Julie, perhaps for you, you know, in the rare disease kind of ecosystem or urban in the, in the, you know, approval and pricing system. I mean, if there's like one thing that you could change, how would you wield that magic wand.
Julie Tierney
If we could decrease in a, in a scientifically rigorous way and, you know, legal and, regulatory really stable away, decrease reliance on clinical trial. So focus on, on information outside of clinical trials. When we're at this sort of amazing point in, science and technology, we've got, you know, genome editing happening, we've got AI and all of these tools at our disposal.
If there's a way, that we could take what we know about what we know about molecules, what we know about pathways, there's so much that we don't know. But, how the pre-clinical space could utilize that new technology to be more predictive of what drugs are going to work and when, and then how data outside of clinical trials could be leveraged so that we're not, you know, still stuck in, you know, two randomized clinical trials or one plus confirmatory evidence.
If we could figure out a way that we are less reliant on doing experiments in humans, to prove whether or not a drug works. I think that would be amazing.
Jennifer Colamonico
And what about for you? How would you wield your magic wand?
Ben Shand
Magic wand? I've got three little kids, so I'd like to say I'm experienced with magic wands. And I would take a a big swing with this one. Perhaps a little a little broader than the maybe initially asked me. But, you know, as we, we spend too much money on health care in the US and it's unsustainable. And it's created a policy environment where we've had downward pressure on, on spend, on budgets and, you know, ultimately, it's my belief that the spend is driven by the incentives across, our care continuum.
And so with my wand, I would, help to realign and kind of modernize the incentives. And, you know, we want to incentivize towards the outcomes that we want. And the outcome is ultimately a healthier America. And I think that from, an innovation standpoint, we want to be incentivizing great foundational root cause research, great translational research, to bring that innovation to the risk takers who are going to bring it along.
Ultimately, that risk needs to be utilized. And in return on investment there. So we need that to be functioning and working to keep innovation flowing through our system. And, you know, could go on and on about incentives, for, across the care continuum towards the patient, but ultimately having the right to modernized incentives, I think, goes a long way towards achieving outcomes that we're looking for.
Jennifer Colamonico
Good one, not one I would have expected in this conversation, but always a good one. I think, the misalignment of incentives sort of it's amazing how many of these conversations that's relevant, to no matter what part of health care we're discussing and certainly relevant to innovation in therapies and treatments. So I appreciate that. Well, this is a big thorny topic, and I think you both have added some, interesting dimensions here.
So really appreciate your time. And certainly a conversation will continue to have and we'll be watching this space very carefully this year particularly, you know, as Congress takes up these issues and, seeing how they, how they use their magic wand, so to speak, to, to guide through those, they're, you know, they're the new user fees and what that will portend for, for FDA moving forward.
So appreciate both your time. Thank you so much.
For this episode of Vital Viewpoints on Health Care is sponsored by 红领巾瓜报 Information Services. 红领巾瓜报IS is a subscription based service that provides state level data on publicly sponsored programs like Medicaid from the latest managed care enrollment, market share, and financial performance data to up to date RFP calendars and state by state overviews, 红领巾瓜报IS has all the information you'll need to power your initiatives to success.
This podcast was produced by myself, Jennifer Colamonico along with Tiffany McKenzie in collaboration with our guests. The content is the property of 红领巾瓜报.
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Vital Viewpoints is hosted by 红领巾瓜报 Vice President, Strategy and Communications, Jennifer Colamonico.
