Modernizing Clinical Trial Operations With Merck's Jennifer Sheller

On this week's episode of the Business of Biotech, Jennifer Sheller, SVP and Head of Global Clinical Trial Operations at Merck talks about simplifying trial protocols and what she likes about Merck's hybrid functional service provider model for conducting trials in over 60 countries. Jennifer shares her experiences integrating Merck's acquisitions without breaking studies or losing people, using new technology to improve trial operations, and co-designing studies with trial sites for agility and speed.  

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Chapters

• 0:00 Meet Jen Scheller And Merck’s Scale
• 3:35 From Paper Forms To EDC And Beyond
• 9:29 Operating Models: Insourced, Outsourced, Hybrid
• 13:01 How Merck’s FSP Model Actually Works
• 18:08 Building A Playbook For M&A Integration
• 24:20 Simplifying Protocols And Data Burden
• 31:20 Risk-Based Quality And ICH E6(R3)
• 37:02 Practical Modernization: Central Monitoring And Automation
• 43:02 Partnering With CROs And Sites
• 47:17 Trial Diversity And Community Engagement
• 52:35 2026 Priorities And Leadership Focus
• 55:11 Closing And Where To Subscribe

Transcript

Ben Comer: 0:06

Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm speaking with Jennifer Sheller, Senior Vice President and Head of Global Clinical Trials at Merck, a company that invested nearly $18 billion in RD in 2024 and conducts trials in over 60 countries at more than 21,000 trial sites with more than 100,000 active patients supported. A pretty sizable clinical uh operation, I would say. I'm excited to chat with Jennifer about her career path leading up to her current role at Merck and the process for integrating clinical programs that Merck acquires. Um, and we'll also talk about the clinical trial modernization and democratization. Uh, I want to get uh Jen's thoughts on that. Uh, we'll touch on Merck's functional service provider model um as well as what new tools and technologies Merck is using to improve clinical trial operations. Thank you so much for being here, Jen.

Jennifer Sheller: 1:11

My pleasure. Thank you.

Ben Comer: 1:13

Uh, you have more than 25 years of experience in clinical development and operations, uh, beginning as a clinical research assistant in contract research as a clinical scientist at Wyeth before leading portfolio and disease area clinical operations at companies including Sanofi, Kyowa Kirin, uh, and now Merck, of course, uh, both domestically and internationally. Um, Jen, what attracted you first to clinical development as a field?

Jennifer Sheller: 1:45

Yeah, I think like many of the professionals in clinical operations, especially, we sort of stumble upon uh clinical trial operations. I've always loved science. I've always had a passion for public health. My mom was a community nurse, and often in my childhood, she would take us around in different parts of the community running health fairs and clinics, and I was just very inspired by the impact that she made uh in her community. And for me, I always wanted to, you know, build a career in healthcare in some capacity. And so I finished a degree in molecular biology. I realized I wasn't gonna be a lab person. That just wasn't my thing. I had plenty of jobs in college to kind of tease that out. And then I went on straight to get a master's in public health epidemiology, balancing, you know, that public health impact with my love of science and data together. And then really, as I was graduating, I had a colleague who just said, Hey, I'm working as a clinical research assistant at COVIDs in Nashville. I was down at UAB in the South and she said, you should check out this company and this field. It it integrates a lot of what we have studied with clinical research design. And so that was my entree. I interviewed uh at COVANS, which is now Fort Triads, had a few different uh spin-offs from there. And um, I had my first job in Princeton, New Jersey as a clinical research assistant. And I was really attracted to the impact that you can make through clinical trials and also the need for good problem solvers and operational skills. I'm the type of person who likes to get things done on my checklist and get things moving and feeling productive. So it was a great fit for me.

Ben Comer: 3:26

Yeah, well, I would imagine with uh with so many clinical trials going on uh all over the world, you you know, it's I know it's a big job to make all of the trains run on time, but you have to have that kind of personality, I would think, that is really focused on on executing, on meeting very specific goals on a very specific timetable. That was not something that was daunting to you. You you uh embraced that and and enjoyed that kind of work, I guess it sounds like.

Jennifer Sheller: 3:53

Yeah, and I love the challenges because it's not textbook stuff, right? I mean, you have 60 pages of good clinical practice regulation, but then you have to apply that to the real world and not just one country or one hospital. It's um so that was always very intriguing to solve for problems and help move forward clinical trials.

Ben Comer: 4:12

Yeah, and and that means working with people, lots of different kinds of people, lots of different kinds of health systems.

Jennifer Sheller: 4:17

That's right. That's right.

Ben Comer: 4:19

Um, thinking, I guess, back to that early experience at Covance and and all the way forward, you've worked at some other really large companies I've just named. Um, what what are the biggest or or most uh impactful changes that that have occurred in clinical development and operations um, you know, since you got started back in the late 1990s?

Jennifer Sheller: 4:42

I would say the volume of RD that's really exploded over the years. You know, it it's there was a an uptick post-COVID, but it's progressively been increasing uh with the focus on science and RD. I think there's a half a million um clinical trials registered at Clintrials.gov. And so it's just it's exploded. And it was nice to see if there's a silver lining in the COVID pandemic that the public started to understand, you know, how new medicines and vaccines were made. Operationally, I would say, you know, when I we first started in the late 90s, it was um, you know, triple NCR paper. So we go out to the hospitals to make sure that the the records in the hospital system matched what was handwritten on an NCR form. And then as a clinical research associate, you'd be ripping off the forms and however many you could bring back into house. And and so, as in the early years of my my work there, that transformed into electronic data capture, you know. So it's still, I would say, uh an area for modernization because today the the staff at research sites have to enter it into a computer system, into our data collector, but it's really looking at the health record and seeing what needs to be pulled into the data collector. There are some pilots, you know, to automate some flow of the data. It's not so easy because, you know, looking across all these different countries and lack of standardization is an area ripe for modernization. But paper to to the electronic data capture was was a huge one. We all sort of reflect on. And we haven't had, to be honest, too many um transformative changes like that in operations over the years. And now there's really a big push to be more modern technologies moving so quickly. So we're we're on the train uh and moving and changing and working on automation and and things like that. And and I would just I would also say too, you know, precision medicine has been a tremendous evolution in drug development and especially in oncology, it's been game-changing with you know immunotherapies and and really um providing meaningful impact to the lives of cancer patients. When I ran trials many, many years ago in the traditional chemo uh radiotherapy models. I mean, the trials were short because the treatments didn't work. And now, you know, we're following patients for you know many, many years, which is is really incredible.

Ben Comer: 7:04

Yeah, and of course, now we're getting, you know, even better, not just you know, novel cancer therapeutics, but even better, more targeted chemotherapy, and better and more targeted uh radiopharmaceuticals. That's an area that I've been watching and is uh a really interesting one and and for especially for for cancer. Um and I I want to come back to um the idea of modernization uh in just a minute. Um, you know, it I I'm curious about you know you mentioned some of the technologies and the shifting from, you know, the the previous shifting from paper to electronic data capture, but you you know, there's still this sense that that healthcare lags, other industries, you know, there are still Excel files being used out there, still PDFs that uh don't exactly make it easy for for data capture sometimes. And I I I wonder if there's an opportunity for drug development and and healthcare more broadly to kind of leapfrog forward and and maybe catch up with uh some of the industries uh that that have moved forward. Uh there's a whole other conversation there about you know the regulatory restraint and the need, you know, we're talking about human lives, so everything has to be very carefully done. So it's not the same as other industries. Um but I I am curious if if there's an opportunity now, you know, to to kind of catch catch up in some ways and get to a more modern, uh, less complex system for conducting clinical trials? We'll we'll come back to that, I promise, in in a few minutes. But uh I just you know thinking about your uh career trajectory and you know, working at companies like Sanafi and Kiawa Curan, um did those experiences help you think about strategy or or models for clinical trial operations that you bring to your current job? I'm sure that different companies do things a little bit differently, right?

Jennifer Sheller: 9:00

They do. There's similarities, even in small biotech. Sometimes they're like mini pharmas, how they set up their functionalities. But I spent about 13 years at at large pharma at Sanofi and uh went to a small biotech Kyowa Kirin shortly thereafter, before coming back into large pharma here at Merck for over eight years. And, you know, what I really saw in operating models, there was a time in the industry where people, you know, pharma companies hired all their clinical operations staff. And then there was this pivot where, you know, companies felt it would be best to outsource all the operations. And so there was sort of this massive shift to outsourcing, and it's really over time has sort of reverted back and it's a bit of a hybrid now. But what I saw in the large pharma environment was, you know, outsourced um in source works best because you need to be able to integrate directly into the teams making decisions. And having a a company that sort of sits outside that's not part of the team creates different goals for teams, and it's not really a united front, and it becomes a little bit of a finger-pointing exercise, and there's maybe different goals and missions that people are focused on. The outsource models in the large companies is really challenging, but it is needed in small biotechs because they don't have the arms and legs that the big pharma has. So some of that functional outsourcing is really important. So what really attracted me in coming into Merck was through a leader who I worked with at Santa Fe, Andy Lee. So he came into Merck and really shifted the paradigm from outsourced, fully outsourced model to bringing everything in-house. So he brought everything in-house and um built an operating model where we have, you know, 60% headcount through our company and then 40% or so through functional service provider. Um, and so that enables really, and the functional service provider model, you know, in this environment, they follow all the same processes as the Merck team. So it's one team, one set of processes, one set of what do we feel is compliant? You know, what is the level of compliance? We all have the same targets and goals and and really infused integrating into one team. And as a clinical trial site, you wouldn't know if you were working with somebody who has a paycheck from MERC or if somebody has a paycheck for one of the CROs that's in the FSP model. And that's what sites really want. They want a direct contact to the sponsor, they want a direct contact to the person who's really leading the study so they can get quick answers and so that things aren't sort of hopping through different levels and and takes a lot of time and churn to get, you know, the right source of information. So for me, that was my biggest learning, you know, working across um the different organizations and just understanding, you know, how do you bring the best of the talent together in a in a model that's going to work um within the environment effectively?

Ben Comer: 11:52

Yeah, let's let's uh talk a little bit more about the functional service provider model. It sounds like it's one that that you like. I mean, you you came to Merck and we're as a support, you know, the way to support that model, you like that model. Um, how does that uh can you maybe just talk a little bit about how that is set up or how it works differently? Uh, you know, uh particularly in other countries where if you have a you know a local organization that you're working with and on a fully outsourced model, it's pretty easy to understand. I mean, it's a kind of almost turnkey, you just hand everything over to the outsource provider. Whereas with the functional service provider model, you have, as you say, you know, internal Merck employees collaborating very closely with these external groups. Um, is it is it difficult to set, I mean, you're you're working in, you know, 60 plus countries. Is it difficult to set up those functional service provider models in each of the areas where you're working? Is there a kind of playbook now that you have to do it so that you can replicate it and do it easily? Yeah.

Jennifer Sheller: 13:00

Yeah, yeah. And there's definitely a certainly a common standard approach here. And it's really starts with partnership, you know, with the CROs and working together as partners. So the CRO understands the skill you're looking for and the oversight expectations and the standards expectations. And it's coming together regularly to get feedback on what's working and feedback from their staff because everyone brings diverse and and you know, good feedback and interesting ideas to the table. So, you know, you could these big CROs have a massive outreach globally. Maybe not all CROs fit my 52 offices that we have, you know, in in the world. So you have to maybe have this CRO that manages two CROs that manage maybe, you know, this in Europe. Maybe you have different ones for Africa and um and Asia Pacific and the US, but having a core set of CROs that we work with, you know, for functional service providers has really been key. And then aligning on like what do we expect. So we don't we don't human resource manage the staff that come from the CRO. So you have to really develop expectations on what you expect their managers to do and then have a forum where, you know, empowering in the country, for example, where the CRO management team works together with the Merck team so that they, you know, are partnering, giving feedback and making sure they're really working as one team. At this trial team level, it's really seamless. You know, like it's not they're sitting at a clinical trial team meeting and they wouldn't say, oh, well, that that uh uh CRM or country manager is from this CRO and this one is a you know Merck employee. That's that's not how it works. They just it's seamless at the trial level because we're again, we're all following the same standards, processes, Merck email, laptops, equipments, iPads for monitoring. So it's it's really integrating uh as one team and and it works. And that's again, that's really what attracted me to come um to the Merck uh organization because of this operating model build and because of the challenges that I saw in the outsource model. You know, if you think of outsourced model, typically it's you contract study by study, right? But that's not how research works. Like so if you have unitized pricing for a given study, X number of monitoring visits, X number of phone calls to a site, that's not the real world because you might have a safety signal where you need extra monitoring. And then if you're in these unitized or or you know, um outsourced contracts, then you have to worry about change orders and then versus flexing your staff across the trials because as one trial sort of dips, another one's gonna pick up. So you can have flexibility and agility to use your resources in a real world environment. And that's that's how trials work. You need to sort of shift folks around and it doesn't it doesn't work well when you have a large-scale volume of trials and then you have to sort of unitize across um each one.

Ben Comer: 16:02

Yeah, right. And it makes sense what you said, you know, about having some core uh CDMO partners that, you know, once you've kind of set up this arrangement, and then you, you know, for example, want to go into an adjacent market or want, I guess if it's a market that that particular CDMO is working in, then they already know, you know, the the arrangement is already set up, the process is already set up, and it's easy to kind of seamlessly move into a new trial, into a new market because you already have kind of the working orders established. That's exactly right. Um, you joined Merck in 2017, uh Jen, and uh initially I think worked on integrating acquired companies RD activities into Merck's RD operations. And and this is a topic I think that uh the business of biotech listeners will will be interested in in hearing from you on because of you know the amount of deal deal activity is is you know one of the one of the positive things in the the kind of broader funding environment uh that's happening right now. The the IPO market is is sluggish. There are a few happening, but it's still fairly slow. But we are seeing deal activity kind of pick up a little bit. I wonder, you know, what you could say, Jen, about um your approach and and Merck's approach to integrating companies. Maybe um you could use, for example, some of the companies that that you worked with when you joined, uh uh Peloton Therapeutics, VLOS Bio, uh Acceleron. What does that integration process look like?

Jennifer Sheller: 17:36

Yeah, and maybe I'll start, you know, I'll share the Peloton example that they came forward with a product that we got our first approval within two years of acquiring Peloton. And that's really, you know, our our model is focusing on preserving the science and the expertise, hence the reason for um acquiring the company. And, you know, it in some of the integrations, Peloton was finishing their phase two, and we we started the phase three in our model. So that was a little bit easier, although they had an ongoing registrational phase two, uh, where we had to really keep the team intact. So it's, you know, and when when biotechs get the word of acquisition, you know, there's probably mixed emotions depending on the levels, but most people are worried about their their um their jobs, right? They're they're supporting their families and it sets a bit of panic. So the first thing, you know, as a leader in approaching an integration, and I was like the operational lead for RD, was really getting out there face to face. It's invaluable straight away. Um and just making sure that people understood the the ethos of our company and how we're a people first company and high bar of ethics, and you know, we will make sure that people are cared for in this environment. And that's what we did, and we made things very clear on retention and we wanted the talent to stay, and we made a concerted effort to interview everybody who wanted, you know, to stay with the company and where there could be a potential fit. And that's not always the case because the profiles perhaps at biotechs largely um aren't always interested in in coming in into large pharma. But the face-to-face piece and the connection is key. And then really understand what you're getting, making sure you have a robust sort of um due diligence debrief with your broader Merck team who's going to help help to help shepherd um you know the acquired company in through uh through all of the the Merck systems and processes. But what's really important is doing an assessment. And this is, I think, where my background comes into play because I've done insourced and outsourced. I'm not stuck on one company way of working, but looking at, you know, how trials are running and deciding like what's really needed to move into the Merck process and system, probably things like the safety database over time. What's okay to keep as is because it is GCP compliant. It might not be the way that you know Merck would do it in their model, but what can we keep running and keep that pivotal, you know, registrational phase two going? Um, that was a rare disease indication that got got approval. So um so it's really having sort of that pragmatic approach and also approaching, you know, the the biotech staff that, you know, we're gonna learn from them. It's not just us coming in and and taking over and acquiring, but what can we learn from you and and approaching in a in a collaboration way. And then you got to make sure that each function that supports clinical trials um has their own sort of playbook of of things that they need to go through to make sure that they have covered and and some of the fundamentals in in processes for clinical trials so that we're mitigating any risk if there's any gaps. You know, a lot of times it can involve re-looking at the CRO contract. Was it too skinny, too light? Do we need to make sure that there's enough monitoring built in here and so on and so forth. And then having a kickoff with the outsource parties as well. So it's all about you know connectivity, um, the people component, but then really bringing in you know the process without disrupting, especially for in-flight. Acceleran had a large phase three program that was probably the most challenging integration. So we we really had to preserve and make sure that those studies were supported and running without trying to murcify things as we say and and and shifting you know ways of working. There's some things inherently that you just have to move over but by and large in operations where you know you can sustain and maybe enhance a little bit of the standards was really the approach we took and then building a governance so you can make sure that we have the right controls and and oversight. And you know when I came into the Peloton integration it was um we didn't have a playbook. We didn't have like a standard way of doing it. So we built it along the way and I actually hired one of the my summer interns to extend her stay for a project to shadow us and build the playbook out. We had some consultants come in and it was creating more chaos than um no offense to consultants, but it was creating a lot more chaos than help. And so we had her sort of shadow us and built this beautiful playbook and that's became the foundation and standard for how we um we conduct our integrations from an operations standpoint moving forward.

Ben Comer: 22:16

Well that's uh that's really interesting and so you have a playbook but it sounds like you're also approaching each company you know in a unique looking at them as a unique organization, what they need, maybe what they don't need. And so there is a little bit of give and take it's not like you know it's a complete standardization no matter what phase you're in or what you know therapy you're developing uh there's um you're you know you're looking at an individual company and making some decisions that may not be the same for for each company in terms of how you do that integration. Is that fair to say?

Jennifer Sheller: 22:49

That's fair. And I think you know the respect for people part is really key because I've heard some horror stories of of other integrations where companies just came in and said everyone's gone in three months. And you know for Peloton they got the messaging very early that they had a long transition plan. You know, and in between we would support them to look at opportunities if they were interested in in staying in the long term. So it's it's really kind of reducing that anxiety and taking the you know taking care of people is is really uh fundamental to making it successful because you need people to still be engaged. You know, there there's trials that are active and running and you're you're you know as as our company we weren't ready to just jump in and take over. We had no idea ways of working processes and it's not all cleanly outsourced to a CRO in many cases. A lot of times the biotechs will have different functions running certain sections on their own process and it's a lot of um mixed ways of working that you need time to understand and and get your team on the ground. And I would say you know for Peloton defending an inspection two years after integration it was really important that we still had Peloton staff with us to help explain some of the history and that was that was invaluable. And that's really only possible because we approach them you know cross-functionally as one team to to really come in and and value their experience and and delivery.

Ben Comer: 24:12

Great. I mean we've seen some and I I think it's less com I see it less commonly now, but um larger pharmaceutical companies who at times I've seen in the past acquire a company and say we're gonna let this company work completely independently uh we're you know we're gonna be we're gonna be here for support but we're gonna be sort of a uh hands off and I think you kind of alluded to the challenge with that type of arrangement. I guess I'm thinking you know of Bayer and a number of uh companies that they uh acquired kind of in the cell therapy area. But uh what you know what I guess is the the challenge with doing it, running it that way, uh letting a company be wholly independent um what you know what what difficulties I guess are are presented by by that arrangement versus a kind of custom integration that that you're describing?

Jennifer Sheller: 25:06

Yeah I guess there's a lot of different models of of how you can approach it. And I think you know a standalone model can preserve a therapeutic area maybe that the company doesn't have you know it would take a tremendous amount of effort to to build. And I think having the right governance model in place that can certainly be successful too. But um where you're integrated like for oncology we have a lot of experience you know we brought in the HIF2 alpha inhibitor from Peloton and renal cell carcinoma and VHL was our our first indication we had a very well established oncology therapeutic area to integrate into so um you know it just probably depends on the the breadth of the company's experience because it'll take a lot to upskill in in a new therapeutic area.

Ben Comer: 25:50

Are you is Merck uh currently you know in terms of uh acquisitions I'm not gonna uh ask you you know who who Merck is going to acquire next uh but are you focused kind of on those seven key therapeutic areas plus vaccines or or does you know Merck think about acquiring companies beyond you know areas where you're you're currently focused? Yeah I don't know that I could speak well to that I mean our focus is following the science uh and bringing the best value to the patients we've had a lot of diversity in our acquisitions you can look at immunology that was an area we haven't been in in a while with the Prometheus acquisition for example so uh we have quite a diverse portfolio uh as it stands today and growing um clinical trials you alluded to this uh earlier have gotten more complex over time uh driven by new drug modalities uh new regulatory designations and pathways new scientific discoveries uh among other things regardless of company size um developers are looking for ways to simplify and modernize clinical development um to be as efficient as possible especially in a time when when funding is is not always easy to uh uh obtain for uh for smaller and mid-sized biotechs in particular um but they don't want to miss out on potential value that a a new development candidate uh represents what are your thoughts on how protocols um can be simplified yeah and this is I would say really a huge opportunity in the industry because we have this bad habit of of taking protocols and copying and pasting you know similar indications to the other and um bringing forward maybe some extensive data collection points or inclusion exclusion criteria that aren't necessarily needed.

Jennifer Sheller: 27:45

So we are focused on protocol lean design as a key initiative or objective for our development organization. And it really needs to you need to start with the end in mind, you know, that we have to stop the copy paste and you know what particular research question are you answering? What do you need to answer that question from an endpoint standpoint? We have a tool and where you can plug in the schedule of activities to met that measures site burden and patient burden and looks at it like in a competitive landscape to say you know if you have a phase three and this indication that what it looks like from a burden score compared to you know other programs and and really having discipline to to take things out. And the the other thing I think we really need to think about is just you know as you think about the ICH good clinical practice framework it's it's fit for purpose focusing on on what matters and and being uh very cautious to add any extra burden into the system with exploratory endpoints for example and and maybe even some of the secondary do you need all do you need to assess it in all patients in a phase three or could you do a substudy um do you need your visit frequency you know every two months or could it be you know could you have some flexibility with your visit windows? Could could there be visits that are done remotely and built into your schedule events so you know easing the burden for patients. But protocols are becoming more and more complex and and this is really an area that we all have to double down on. There was a a really interesting tough study recently that looked at data collection and you know over the last decade or so I think they quoted that we've increased data collection and trials more than threefold. I think it was like 3.5 increase in in data collection. So it's not just you know specifically the processes and visits procedures that you're putting into your your designs, but also the volume of data that you're asking to correlate for that. So we have to have good discipline and rigor. And then you know when you think about protocol simplification, the whole ecosystem needs to be simplified. So as you're you know leaning your protocols, you need to start to think about leaning your data collection so it's fit for purpose and then how you clean the data, you know, we're looking very deeply at how our our teams are querying the data, which adds work to our research sites, right? And so do we need to query all data the same you know can you tier your data so it's more risk proportionate. So really looking at I would say the the full ecosystem downstream of of the protocol development and and simplifying we've just become incredibly complex uh over time and and trying to answer a lot of research questions in in one design and where we can you know focus on on what's most important will really help everyone at the end.

Ben Comer: 30:41

That's a really interesting it kind of reminds me of I think you know a period maybe five or 10 years ago where there was a a lot of excitement about um new types of data that could be captured and there was a feeling almost that you know the more data the merrier like let's just you know like capture as much data as we possibly can and then on the back end we'll figure out you know where where the value is but you know what you're saying is that that you know complicates trials. It it makes them perhaps last longer, cost more and that there needs to be you know a kind of uh trimming you know a bringing this you know better you know focusing it more to answer a specific question that you're trying to ask rather than you know just simply capturing as much data as you possibly can.

Jennifer Sheller: 31:28

That's right. And it's and think about the burden you can think of like the eco assessments, the um the outcome assessments or the pros they would call them patient reported outcomes. So you know trials have added lots of those uh into the system that that collects a lot of data and then that requires quality control and cleaning and reconciliation. So that's for you have to add that work into your team then you have to add that work into the clinical trial sites. And what I've noticed just over the years is while we've thrown out a lot more data, we haven't developed cleaning mechanisms that apply the technology rigor of automation to do this in a very efficient manner. So you see a lot of sort of old skills being applied to clean massive amounts of data. You know you still see sometimes Excel for um diary information that's collected in you know thousands of patients and so this is where we're really working to support our teams and bring more of the the technology skills but we need it from the vendors too. There's a lot of vendors in the clinical trial environment you have lab vendors, you have the ECOA vendors, you have the IRT vendors I mean you probably have seven or eight different vendors in any given study and that's a lot of data collected across them. And what I'd like to see more holistically is just mechanisms to automate more of the reconciliation versus putting the burden on you know the sponsor teams to try to figure out and and build tools. And and one area that that our industry is really trying to figure out these days is how do we leverage audit trail data in systems to give us and we have to start to do this because it's becoming it's become part of the the good clinical practice guidelines, but you know how can we do this at scale with efficiency to give us quality control signals in in our trial oversight. So all that new data has come in I would say it's been a bit of old fashioned cleaning and and reconciliation that's really an opportunity to not only trim but then you know identify more efficient ways to to do quality control of this massive volume of data.

Ben Comer: 33:38

You mentioned the ICH the International Council for harmonization I believe can you would you mind just mentioning how you know whether Merck works directly with that group or or how you use the various tools and guidance that that they provide.

Jennifer Sheller: 33:55

Yeah and so that really the ICH good clinical practice framework is the international standard for conducting research. So I mean we're all following ICH good clinical practice that's the foundation and that gives the common core of how research can be done globally with a common set of standards. The US is an adopter many of the large countries are adopters and it's it's the framework you'll see in probably any any global company so they've they they haven't updated the good clinical practice guidelines quite very often for a long period of time. I think it was like 10 years before the section around clinical trial oversight was updated. And then they updated again in a couple years. So we had a recent update this year and that's revision three and you know this is I think from 1996 of revision three and and it's it's taken that long of time. But revision three is really I would say a tailwind in in the clinical trial operational delivery because revision three is emphasizing risk proportionality as a principle, not an option, but as a principle of how research is conducted meaning you don't treat all of that all of your data the same you focus on critical data, critical data and processes with a higher amount of rigor. You take more risk-based approaches uh you know in your data cleaning and quality control and our industry has really struggled with that over the years. You still see some organizations doing a hundred percent manual cross checks what we call a source data verification. So sending people in the field to do 100% checks of what's in your collector versus what's in an electronic health record. And we found even 10 years ago plus there was a a paper that you know really kind of dispelled the the myth of the value of doing that cross check with Transcelerate which is a consortium of of pharma um you know working to advance our industry and bring forward best practices and they had a really interesting publication and study where they showed only like two to three percent of critical data changed from all of that effort doing that cross check. But yet you still see uh organizations, many organizations are shifting away from that and some are even thinking do I need to do that check at all? Can we just determine the outliers and anomalies and and centralize methods. So we're sort of playing us we're playing around right now we we don't do 100% we're looking to see how we can do more central monitoring to um to sort of support quality control measures. But yeah it's it's really um lots of opportunity it's been a slow evolution but I really think today with the pressures the pricing pressures in the in our pharma landscape but also um you know the regulatory changes and pressures the need to go fast, it's not optional. And technology is certainly providing a lot of opportunity where we can take this and run and and do things differently.

Ben Comer: 36:52

I think this is a a great segue to the idea of modernizing clinical development. It's something that I've heard uh commissioner FDA Commissioner Macri talk about recently the importance of modernizing the the clinical enterprise um other biotech and pharma leaders have have have mentioned it and I I'm curious what modernization means to you uh in this context and maybe we've already been talking about modernization but what what does it mean to modernize uh clinical trials?

Jennifer Sheller: 37:22

Yeah I would say from an operational standpoint not a design standpoint because there's lots of lots of opportunity I'm sure that's you know in the in the strategic thinking of the FDA but you know when I think about modernizing clinical trial operations um I think about simplifying with rigor based on that R3 update you know where they're with really focusing on risk proportionality and making sure that processes aren't overly heavy so we've sort of what happens I think over time is you know you develop processes, you get an inspection, oh there's a finding and then you apply you know a lot of change and extra checks in place and you know coming back, is this worth it? Is it working? Is it adding value? Like really for me right now in our environment we have to challenge our ways of working and you know I'll give you one example we have uh in clinical trials you have to collect deviations from the protocol. So if a clinical trial site isn't compliant with your protocol you have to log all those deviations. Some are not important could be you're a day out of window for your visit, you're late on something and some could be incredibly important like there was a your patient wasn't consented for a trial that applies a different level of focus. And you know in some of these processes we apply the same amount of rigor to those non-important protocol deviations as we do to the important ones. So for me that's a dial down. You know that's where AI can help me trend the non-important deviations for the oversight. So when we see trends you know using natural language processing because there's a lot of qualitative text and how these things are reported there's categories too but to get into the meat you have to dig in a bit I think that's where teams are struggled. But here this is where AI can help, you know, directing our teams to trend better and to say hey this is a trend we're seeing in ECGs missed at week 13 and um sort of understanding the patient journey and the flow and and maybe digging in there versus going, you know, patient by patient and in the review and and providing maybe a bit too much resource and effort. So simplifying with rigor, focusing on what matters most, we are really focused on redefining our risk-based quality management operating model, which is really looking at how do we define what is critical first. Because you know a lot of times you can see teams identify 50 different things that they think that are critical but that's not providing you know sort of that differentiation focus and you need experience to help teams with that to say this is your primary endpoint, key secondary, this is most critical, you know, and and really try To help our teams narrow that down and couple that with, you know, highly robust oversight, coupling more of that central monitoring type of activity. And that would be programmatically cross-checking data versus sending that person in the field, you know, just relying on that type of check. And then thinking about like your other tiers of data and what types of quality checks you want to put in place. It could be, you know, maybe you apply an edit check on a data that's not critical and you issue questions to the site if it's out of a range and then you leave it when the site responds versus, you know, continuing to sort of perseverate on it and applying different decisions that apply true risk-based methodologies into ways of working. So that's how I view modernization. You know, it's it's really applying more fit-for-purpose ways of working. You have to document it. You know, you have to be very clear on your decisions and um and documenting. But there's just been a lot of, I would say, old-fashioned ways of working and traditional ways of working. I think an over-reliance on manual checks that happen in the field and how that's all documented versus modernizing through, you know, programmatic reconciliation, automation of checks, all that external data that I mentioned that was coming in and making sure teams have a dashboard where they can see this site is missing, you know, they didn't do this procedure at this visit and they're red. You know, they need a follow-up. You have to send that field person out to retrain and get get them back into compliance. So it's um that to me is really where we can we can be more effective, efficient, and leveraging uh technology to how it can best support our teams. I I have one, you know, funny story. We bring a lot of interns in every summer and really trying to infuse blending sort of tech skills and clinical scientist skills. And um one of our interns shared with me, I said, so how's it working? Do you have any ideas like on where we can automate more, where you're seeing a lot of heavy Excel tracker, you know, movement and email updates and things like that? And she said, Jen, she's like, it's not even using just Excel. She's like, they're not, I see people using Excel as a Word document, like typing a lot of text into Excel and not applying formulas. So there's a lot of opportunity to to really help and and make things you know more um automated and efficient. And it's it's people just have to have an open mind to learn from others and see how things can be done differently.

Ben Comer: 42:33

And so uh at Merck, when you're wanting to maybe introduce new tools uh to improve this process, dial something back, as you mentioned, is that a conversation that you're having through the functional service provider group of folks? You're talking to the site as well as internally with people at Merck and kind of getting an agreement uh and at least, you know, informing everyone, you know, how something is going to change going forward. Is that right?

Jennifer Sheller: 43:02

Yeah, and we and we have exactly we have a process owner network. So like owners of specific, you know, we have all these processes to follow in in in clinical development and how you run your study is governed by your processes, which are in line with those ICH guidelines that I mentioned. So for me, it starts with the process owner, make sure they have the right training to do lean design and efficiencies, and also couple them with technology experts so they can look at the process from first a simplification manner, but then where can technology help perform some of these areas of the process? The example I mentioned with you know the deviations and using AI to do trending and um, you know, it's sort of coupling and mirroring those types of skills, but then we don't make decisions in a vacuum. So uh we engage our teams, those that are working at the clinical trial level, and that could be the FSP resources through the CRO, or it could be our own headcount staff. And if it's a process that involves or impacts our clinical trial sites, we do survey our sites every year to say what's working well, where do we need to improve? But we also have a network of sites that we tap into and sit down and walk them through what we're thinking. What do you think? Does this make sense? And we've had some sites who you know came forward and said, hey, look, we're not going to do this trial unless you do apply the R3 changes and having non-physician um investigators or sub-investigators in the trial. We can't do this study unless we can use our nurse practitioners. So we brought it back to our development forum. It's beyond operations, and we changed our process, you know, where we now have built into the protocol where it's appropriate to have the non-physician um sub-investigators. So it can go both ways. You know, it can be driven by us, and as we learn through through our peers, we're part of a lot of industry consortiums, but it can also bubble up from research sites around the globe to tell us, hey, um, this isn't working. This we need to change, and and we're open and we listen. And um, having a seat at the table from our clinical trial sites is so important that we don't turn into ivory tower decision makers.

Ben Comer: 45:14

Is it possible for sponsor companies that you know maybe don't have this functional service provider model or working in more of a fully outsourced model to uh communicate with their CDMO partners and have that kind of information exchange and even make some changes? Uh, I it may be more difficult. I don't know, but are there I is there any advice, I guess, that you would have for perhaps smaller biotech companies who are working on more of a fully outsourced model, you know, how to think about and implement some of these things?

Jennifer Sheller: 45:47

I mean, you know, from my experience in the biotech and working through all these integrations, my advice is treat your CRO like a partner. Because if it becomes a very tactical relationship and fear-based and finger pointing, you won't get anywhere. I I had one environment where I really had to turn around some of the relationships and the team dynamics to make sure that we were listening to the CRO. They had, you know, they had very valid feedback and points and behaviors that we needed to change, you know, on the sponsor side. So I would just really encourage you approaching it like a partner. And and every sponsor, biotech or big pharma, should be sitting down with sites regularly. I think biotechs do a nice job at getting out there because, you know, at all levels, they're really vested in partnering with sites and getting their feedback and and having the CRO sort of uh around the table as one team, even if it's not an FSP model. I think the behaviors and the way that we work together in a partnership way just goes a tremendous way. We every year we have a forum where we celebrate, we bring in all of our um supplier leaders, not just FSP, but the labs, all the key um vendor leaders across the ecosystem that we couldn't, frankly, do this work without. And we come together and we talk about like, you know, the vision and the strategy, our portfolio. And then we also celebrate, you know, how where things worked well. And um, you know, we have forums where they're bringing forward, they've got a bigger line of sight across the industry too. Like, where are they seeing ways that we can improve? So for biotechs, it's you know, it's just be open um to feedback and operations makes a difference. You know, it's not just the science, the the beauty of the science, uh, but it's being able to execute in in a feasible manner uh really makes a difference. And I I would also just add when we talked about simplifying protocols, one key area is bring the sites in early. Don't just hand them a final protocol. Like walk the protocol with your sites, maybe walk it with your lab vendor to make sure all these you know um uh shipments are feasible across the different specialty labs and what the turnaround time is going to be and how that impacts, you know, a patient who's waiting to know if they're eligible for a cancer therapy. So, you know, taking the proactive steps up front just goes a tremendous, tremendous way.

Ben Comer: 48:09

And listen to their feedback too, right? And you know what what they have to say based on you know their experiences working specifically in those areas, yeah. Um Merck uh recently launched a campaign called Let's Talk Clinical Trials, uh, which I think is uh aims to expand the tent, um, the number of people who participate in clinical research. Is clinical trial diversity an area that that you are focused on in operations?

Jennifer Sheller: 48:38

Absolutely. And and it's always been it's always been a core of of how we work. And you have inherent diversity by our country footprint, but we also have you know a special focus on our US population to make sure that we're not you know approaching all patients in the same way. You know, educational um methods need to differ and and also engaging in the community has been a big focus for us. You know, typically in trials, you focus on the site, you know, but we have to go broader than that. And when you look at the US as an example, I think is it five to eight percent of cancer patients participate in a clinical trial, whereas many would be interested if they were asked. And, you know, I don't know about you, but you know, I know um friends who've had cancer, and I'm trying to explain to them like where clinical trials could be. Like it's it's very difficult for a lay person to understand how to even access a trial. It's not all the healthcare providers are are going to be giving recommendations for potential trials for patients. So education is key. Uh, let's talk trials is something that we created for the industry, for clinical research as a whole. It's not specific to Merck, and it's providing education on what are trials, perhaps dispelling myths on what people think trials are, hearing from patients, hearing from community members, understanding all the rigor and ethics reviews that goes into approving a clinical trial. And it's really just putting it out there, you know, in basic terms so people can understand that it is a care option. Um, and here's how you find, you know, ways. Clintrials.gov is a bit of a nightmare to sort through. We have a beautiful website, a clinical trial finder. I know other companies um do as well. But the more we can educate as a potential care option, especially when you know patients are suffering and there's there's they're out of options, you know, to ensure that this is better understood. I think during the COVID era, you know, the public really started to understand, but that fizzled out a bit. So we have to really have more intentionality in our communication about what clinical trials are. I love Let's Talk Trials, and it's it's something that many of us who've been in the industry for a while have been really um yearning to see. And I'm really proud of our company for putting the effort here.

Ben Comer: 50:57

Yeah, well, I mean, I would think part of it too uh has to do with engaging and educating community uh providers. And I I wonder if, you know, you this ever, you know, thinking about community providers and making sure that, you know, they're even notifying their patients about potentially, you know, that the provider themselves knows about the trial and that they're they're uh identifying um their own patients to potentially participate. I mean, I wonder if that ever, you know, calls to mind some of those early experiences you had uh with with your mother going to uh you know a community health center. I mean, is that something that you're thinking about as well?

Jennifer Sheller: 51:35

Yeah, I and you know, I would love, my dream would be like when you get your you know, electronic health record, it was a printo, you know, from your visit, you get your visit summary. Wouldn't it be great if it sort of automatically populated active clinical trials in your vicinity for maybe a disease that you're suffering from, at least to kind of allow the patient to have a choice and maybe a barcode to get to let's talk trials so they could say, like, what is a trial? You know, how do what what does this involve and and really to make it automatic through the healthcare system to me would be the dream. Um, you know, continuing to educate, educating communities. It's a strategy that we've we've deployed through many different partners. This is one, you know, method of of doing it. And we've also had intentional boots on the ground to to do it as well. But we all need to put our efforts in here to to continue to educate and and allow patients and their caregivers to to make choices.

Ben Comer: 52:31

Right. Right. Um, well, we are uh coming up on the end of our time here. But before I let you go, Jenna, I wanted to ask uh about next year, looking forward to 2026. We're coming up on the the end of the year here. Um, what are some of your professional priorities uh at Merck? And then um, what are some of your personal priorities?

Jennifer Sheller: 52:52

So um, you know, professionally, it's delivering this diverse and vast portfolio with high quality. And we're really focused, as I mentioned earlier, on resetting our operating model with risk-based quality management. So balancing more of the central monitoring with the site, that's going to be a really important focus uh for us, it is right now and for implementation in in 2026. So we're using our roles most effectively on the most important data. So that that's really key. I would say creating an environment where we simplify with rigor and we automate at scale. So I build an automation hub and I'm pairing it up through the functions in our organization. They all sort of have matrix leads into the hub and um building this now into process officially. So it's, you know, we've had a good time with experimentation on things like co-pilot and tools, and there's different adoption of great tools like Power Automate and DI and things like that. So it's it's really simplifying with rigor, automating at scale and making our work more efficient and productive so we can do more because we know we need to continue to fuel our RD engine. And, you know, from a personal standpoint and and and you know, professional as well, is really taking care of my leadership team, making sure that they have the right skills to to help their teams optimize. I need growth mindset and and people to get behind why we need to evolve and and modernize. So it's it's making sure I'm bringing my leaders along and supporting them and then building the future leaders. You know, it's it's really building the future leaders of clinical trials. It's to me, pairing up some of the these heavy tech skills with the clinical skills so that they can come together and sort of have a best of skill set for what the this environment needs. And, you know, always as a leader, I think it's important to take care of yourself physically and take care of your health so you show up well for your team. So that's that's a commitment to me, as well as um making sure I'm upskilling my my digital acumen uh in this environment too.

Ben Comer: 54:55

Right. Excellent. Well, thank you so much for being here, Jen. I really appreciate it.

Jennifer Sheller: 55:00

Thank you. Thanks, Ben.

Ben Comer: 55:01

We've been speaking with Jennifer Scheller, Senior Vice President and Head of Global Clinical Trials at Merck. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out new weekly video casts of these conversations every Monday under the Business of Biotech tab at life science leader.com. We'll see you next week and thanks as always for listening.