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Joseph Kim:
Welcome to Clinical Research Confidential. On this show, we highlight and demystify the inner workings of this greatly misunderstood activity called clinical research. Now, why is clinical research important? Well, it’s the basis for nearly every modern remedy for sickness and a growing method to build trust and solutions meant to optimize health, but it’s not for the faint of heart. And so on this show, you’ll hear what it really takes to succeed in the clinical research game. I’m your host, Joseph Kim, and I’ve spent over 23 years in the clinical research industry, now serving as the chief strategy officer for ProofPilot. Get ready for some adventures as we look into the underbelly of clinical research.

Joseph Kim:
For our final episode of the season, we have the one and only Craig Lipset who, I won’t even try to introduce him because if you try, you’ll just run out of time because there are so many different titles that you have. Greg, welcome to the show.

Craig Lipset:
Good to see you, Joe.

Joseph Kim:
As I alluded to, you do a lot of different things, and I remember you making a good-natured joke about me because I was recording music. You’re like, Joe, how do you find the time? And I’m like, Greg, come on, you do all these other things. So how do you find time? Anyway, I want to get into that for sure. But before we start, I don’t think people really know who you are. From the beginning, what is your origin story like? Your LinkedIn only goes back to the senior director level and few people leave college and all of a sudden become senior directors at companies. Tell us more about your education and what you studied. What was your first job?

Craig Lipset:
That’s a great question. My first job was scooping ice cream. My education was initially at Brandeis University, where I studied music theory. We can dig into that and your alternate career as well, Joe. But my night job through college was doing EMS work around Boston, so I always had this inkling for medicine. And like a lot of kids that age going down that journey thought, I guess that means I’m supposed to go to medical school. And along that journey fell for the field of public health along the way, the idea that you could impact the lives of many rather than just in that 1-to-1 relationship of traditional healthcare. And it was when I took this detour and went to get a master’s in public health and epidemiology that I started to see more and more of the economics and the impact around drug development and pharmaceuticals. I was just amazed at the dollar that went into drug development. It seemed absurd, but it also seemed like an area of a huge amount of opportunity. With so much money getting thrown into the effort to create one new medicine that there had to be some cool opportunities in there to do things better or differently. I started to look into careers in consulting and management consulting and wasn’t an MBA, I was an MPH, but I had it in my head that if I went to a consulting firm, I could see how lots of different drug companies operate, which ones make decisions in one way versus another, get this little smorgasbord of different experiences, but didn’t really have the background for like a BCG coming in as an epidemiologist out of grad school. So I discovered this other sector that I didn’t know existed, these things called CROs, and I navigated my way over to Parexel and Waltham, and very early on I was hired in as the project manager for the medical imaging department that had just been created, and there was one project manager and that was me, and the guy that was the director of medical imaging who created it was Marc Goldberg. Marc grew up to create Perceptive Informatics, he was later the president of Parexel, he had a storied career and I learned a tremendous amount. Riding a lot of that wave with Marc in terms of getting exposure to this opportunity for tech and tech-based services to make a tremendous impact on the field, and quite honestly, that CRO experience was really amazing. It gave me that visibility into, wow, this biotech company makes decisions based on trying to build unanimity across the entire organization just to make a go decision, whereas someone else just makes it entirely top-down. It gave me this visibility into that decision-making that I was really curious about and the different approaches the different pharma and biotech were taking. I stayed at Parexel for about eight years and really started this step in my career that focused on white space, this appreciation that lots of smart people in the organization doing smart things, but very often they’d start to get compartmentalized in their little domains and it would start to leave a lot of white space in between. And because I would gravitate to the white space that people weren’t doing, people left me alone to create and just do things. I wound up running part of that imaging business and then part of Perceptive Informatics from a business development perspective and got a lot of experience there, but felt like I needed some ownership over a molecule and made this leap into biotech. Went to a young venture-backed biotech company, called it Nexus Therapeutics. I was the VP of Clinical and Regulatory, which sounds grandiose, except for the fact that there was nobody in clinical and regulatory. It was 25 scientists at the bench, a really smart chief operating officer and then me, tasked with, get this thing into the clinic, whatever that means, whatever you have to do.

Joseph Kim:
What’s the year at this point when you went to this?

Craig Lipset:
Yeah, that has to be around 2005, 2006, and I started to appreciate the network that I had coming out of Parexel because I needed a lot of friends to be able to call on to figure out how to get an R&D filed and get a phase one study started in the clinic with the department of me. And it was funny, when I left, at that company, and it rebranded as Adnexus Therapeutics, it was bought by Bristol-Myers. I remember I went to go interview for a job at Pfizer and somebody there said to me, I don’t know that you really have hands-on experience with drug development at that biotech company. When I say I submitted an IND, I printed it, I put it in the FedEx box, I drove to Kinko’s, and when the FDA called the phone number on the cover, my phone rang. I don’t know how much more intimate you could be with the drug development process than that.

Joseph Kim:
Although what they were saying was like, you didn’t run the trial. You didn’t do, you know, the nits and nats of the actual trial. Is that what they were alluding to?

Craig Lipset:
No, I think that they were thinking in the big pharma process of having this big machine and having to navigate. To a person in a large organization, drug development is a very complex process and it involves a tremendous amount of internal navigation. You’ve lived it at Shire, you’ve lived it at Lilly, at a small biotech company, you were it. So in some ways, you could say it’s easier, right? There’s not a lot of governance and bureaucracy, but in terms of knowing the details of what’s involved in the process, you’re the one printing off the IND, which is a pretty cool experience. So it was around that time frame I was looking, thinking, well, I should get some two years of big pharma experience on my resume. I hadn’t had that. I had this CRO experience, I had a little biotech, two years of Big Pharma.

Joseph Kim:
Why do you think two years was important? Did you have a destination in mind or were you just, this is a good check box?

Craig Lipset:
It was a check box. I thought that, for whatever it was I wanted to do next, I wasn’t really sure. I’m not somebody that had a 15-year career plan, but I figured I looked around and saw other people that I thought were impressive, and they usually had a couple of years of pharma and less than two years, seems like it was a little transient, so two years is what I’ll do. So I don’t know, it made sense at the time. We were living in Massachusetts, there was an illness in the family, we wanted to get back to the New York area, so I took a job with Pfizer that involved a relocation package that said, you’re going to be with us for two years. So I said, this is, this all works, right? The numbers add up and then you blink and two years turns to 12, and you think, how did that just happen? How was I at Pfizer for 12 years? What happened to that plan of two years and then move on, and I think what happened for me at Pfizer was there were so many reorganizations and these reorganizations would do one of two things. Either people would duck their heads and stop coming in to work in the parking lot would empty out, or you could show up, especially if you’re somebody new there without a lot of skin in the game, and say, hey, maybe this creates some opportunities that again, maybe there’s some white space associated with this reorg. That’s how I created this clinical innovation function at Pfizer. Nobody really had it on the org chart, but it was white space and I raised my hand during a reorg and was able to make that happen. And, you know, in large part, look, I don’t want to make it sound like oversimplistic, it was in large part because I had invested in building a really good network within the company to build up some trust early on. A lot of my takeaways from this journey are this importance of having a good network within and beyond, you need a good network inside of these large organizations. There will be reorgs, you can’t rely, you may have the best manager on the planet, but you can’t rely on that person being there long-term. They may find other opportunities or the organization may change around them. You need redundancy and you need a network, and that experience with that young biotech, the importance of having a network outside of your company as well. And this takes work, right? and some personalities that may lend themselves to better than others. I think people, Joe, assume that people like you and me are extroverts, so maybe this is natural for us. I’m absolutely an introvert. You don’t see me hanging out at the bar at conferences. I’m in my room having room service by myself. I like to think to have these very exclusive dinner meetings, very exclusive, only one invitation.

Joseph Kim:
Me, myself, and I.

Craig Lipset:
But it takes work. And you’ve been amazing at this, Joe. And I think that for a lot of people, it’s very easy to just be focused on the task that you were hired for, but in building up these networks internally and externally, I know have been, just an important part for my entire journey to date, and I think we’ll probably continue that way.

Joseph Kim:
Yeah, a couple takeaways I’m hearing in addition to what you just said is, and I often think about this too, which is nobody cares about your career more than you. And that sounds like a cynical way of looking at the world, but it’s actually a very positive thing. Like you shouldn’t rely on somebody to just lift you up, like because they’re not going to care more than you care. But that also means if you care this much, then they can care this much, right? They can only care as much as you care, and to the extent that you’ve done this, which is care about your career and care about it, it allows other people to care equally to the same degree as you do. I first met you like when you first started that clinical innovation role, and it was fantastic to see somebody with that title.

Craig Lipset:
It was a cool journey. I give a hat tip to leaders like John Hubbard, who is running DevOps at the time, Frida Lewis Hall, who was a great champion for me, being able to pull that together. Other leaders at Pfizer that, like Chuck Kunesh that maybe weren’t quite as prominent, but also just great voices and champions for us to be able to pull that together. And then by leveraging platforms like DPharm as a conference to bring people together and create a really nice community. I don’t know if I should say this, we shared a lot of job descriptions with other companies so that they could build up groups and functions and they had to obviously modify to fit their organizations, but we knew that there was power in numbers and that if other organizations were following similar paths, this was just a win for us all.

Joseph Kim:
While you were at Pfizer, one of the achievements, which came with mixed reviews but I thought it was still an achievement, which was the remote study. And this … use this as a foreshadow to what we’ll talk about later, which is decentralized trials, but can you tell us a little bit about the remote study and what you were trying to do? Let’s start with the year. What year are we talking about?

Craig Lipset:
So I started planning that remote study within about six months of landing at Pfizer, and when I landed at Pfizer, I was in a team, originally it was called Health Technologies, but then I got reworked into a group called Molecular Medicine. So I’m in a group called Molecular Medicine, the mandate for the group is enabling precision medicine strategies for our medicines. And I went off on the side and started to work to define and find partners and allies around this concept of remote, decentralized trial, which we affectionately coined a participatory, patient-centered trial way back then.

Joseph Kim:
But this was a little bit off-center from the role at hand. This doesn’t sound like molecular …

Craig Lipset:
Nothing to do with my job description. I had a boss at the time named Aidan Power, who was really, just let us stretch the definition of molecular medicine and precision medicine and keep stretching that in expansive ways around thoughtful uses of digital and gave me latitude and some cover to be able to do this. It was not my job, it wasn’t in my job description, I just inserted myself. There were some leaders that were owning innovation at a corporate level. It was mostly under IT back then, that were serving as good mentors and champions for me, I was new in the company, so names like Kathy Gibson and …, they had been there for a while and knew how to navigate and helped coach me a bit, but it was really very nascent. So we started to set this up and we tried to tell the story of a decentralized trial, which at the time we didn’t call it that, but that it was really just a string of pearls. We tried to make it feel more accessible for the organization by showing, here are 12 modules that we are going to string together, and these different modules we’ve either done in isolation like an electronic diary, we’ve done incrementally like an electronic consent, or maybe we’ve experimented with a little bit, but nothing here is radical and new. And to try and show that really all we’re doing is putting these already known pieces together to create something new and special, but to make it feel accessible by showing that the pieces themselves were not radical and far-reaching and science fiction for us. Now, a big part of that story then was also pairing up with some external thought leaders like Steve Cummings from UCSF, who together with Anthony Costello, had created this company, Mytrus, based on what we were trying to create. Mytrus was born after we started working together with that group on what this could look like, and that part of the journey really helped me to appreciate the power of an external thought leader amplifying our work. I continue to try to serve that role for friends and industry today because, I appreciate it so much, the important role that having somebody from outside played in helping to validate the things that some of us inside were already saying but needed that extra voice. And with that, we were able to build support with leaders there, like Andy Lee, who was at Pfizer at the time and now leads development at Merck, bringing some fabulous project management with names like Miguel Ori, and bring that to life. The remote trial was initially designed as an experiment. We took an approved drug, Detrol, we took the original registration study for it in overactive bladder and we tried to tinker with it to make it work as a remote, decentralized trial that would take place entirely online. We would have to screen hundreds of thousands of women with overactive bladder in order to enroll hundreds of women who would be able to participate in a study entirely from home. We were probably a little overly aggressive in saying this had to be direct-to-patient, and I think that was one of the shortcomings that we had in this story, because ultimately the systems we strung together worked from a systems perspective, they worked from an audit perspective. The people, when we did, in recruitment efforts, we had thousands of people show up for screening online. The challenge was we took an already existing protocol, so we had very restrictive eligibility criteria. The definition of overactive bladder in a clinical trial protocol for registration purposes is very different from the definition of an overactive bladder in the mind of a woman who is having an overactive bladder, right? Like the clinical grade of severity that we needed was very hard to find, and it was particularly hard to find by going direct-to-patient. If we were more inclusive about going to providers in the community to engage them and their patients, I think we might have had a better chance, but we ultimately spun down the study because our recruitment efforts just were not finding us the right woman with the right severity. So we wound that down and said, we’re going to reboot. We’re going to take what worked and double down and the things that didn’t work, we’ll have to keep tinkering and working at the edges with. But we did try to share everything, Joe, and I think that certainly got us out there quite a bit and hopefully helped to spark a lot of the subsequent investment from a lot of other companies.

Joseph Kim:
For sure, on the most basic measure, I think it was a success. The fact that you actually got it up and running and approved and out the door. You’ve learned a lot with regard to patient recruitment for that specific indication, for that specific protocol. It’s always different, every protocol is its own special snowflake, I like to say. And you can’t just like lift and shift and cut and paste tactics from one to another. I remember the day it came out and, not the day, but the day it was announced and I think it was a SCOPE conference we were all very excited about, and you were going to read out the learnings very publicly, but it’s a big foreshadowing to what you’re really focusing on today as a centerpiece for what you do, which is decentralized trials. But before we get into that, as I alluded to my intro, like, who are you? You do so many different things. Tell us about the exit from Pfizer, because you left a big vacuum there. And it’s still, I think the innovation group still exists at Pfizer, but there’s not like a externally facing recognizable leader as you anymore, so you left a bit of a vacuum there, but it still continues. What did you do? How did you exit there and what are you doing now as a profession? Because you don’t work for any one organization anymore. You work for yourself.

Craig Lipset:
One of my great joys, working at Pfizer, aside from a lot of the great people I got to spend time with, was being able to define a scope for what clinical innovation would go after that I believed in and that was meaningful to me. And so we were tackling digital and trials, patient engagement and experience, multi-stakeholder collaborations like transcelerate and others, partnering with large health systems to integrate research and care. Those were some of our biggest pillars. When I left Pfizer, I didn’t give up on those areas. Those were the areas that I continued to believe in. I had carved those out as our scope for a reason. And so why did I leave Pfizer? I left Pfizer for, I guess, a couple of reasons, but some of them that really jump out are, I think in a lot of ways the organization outgrew having a centralized leader for innovation. I had that title for a while, and suddenly, like I was mentioning earlier, 2 years turned to 12 really quickly and I started to look around and feel like, am I becoming the man that, like some young person, has to come in and they’re going to have to figure out how to navigate around because now I’m so comfortable in what I’m doing that I become entrenched in my ways. That was never my intent or expectation. But I think also organizationally, so many of the areas we had been working on had greater ownership internally, and you didn’t need a central guy named Craig to own them anymore. They really needed to get moved closer into the business, which meant I would have become something more of a strategist than an owner of a lot of these areas. And as I mentioned earlier, I quickly learned it early in my career at Pfizer, people learn to listen to strategies externally much better than they listen to strategies internally. And I knew if I was just going to be a strategist, I’d much rather do it from outside the organization, the odds are people listen better. So I used that as an opportunity and said, let’s see what else is out there. And I wasn’t really sure what that was going to be until one day I changed my LinkedIn profile and added the word former to my title around Pfizer. And I think that’s when I started to see what I was going to be able to do next because of the types of inbound inquiries I started to receive. And at first, my hesitation was people are just calling because you’re the ex-Pfizer guy. They want to pump you for info on how to sell into Pfizer, but it certainly seemed like a lot more than that. And I was able to weed out the ones that were just ex-Pfizer guy and find these ways to continue to do the areas that I believed in, digital patient engagement, collaborations, and different ways to partner with large health systems in the US to really integrate research and care, and I built my own little thing around that. A lot of that has been advisory work, so I do a fair amount of either board work or executive advising that tends to be retained with pharma, with tech companies, with health systems, with nonprofits, and with investors on the venture side, most of all, the companies on the tech side that I spend time with are venture-backed because I like the innovators, the younger companies that I can help guide and influence. And quite honestly, we spend time together as long as I can make an impact, and when I can’t make an impact there, that’s all good. I only have so many hours in the week to be able to do this. So if the impact isn’t there for me to be able to help with, we move on. But then, in the year before the pandemic, Amir Kalali had reached out to me and said, maybe it’s time for us to take this DCT thing and do more than just talk about it at conferences, because we would have recurring panels in SCOPE, at CNS Summit, at DPharm with the same or different people, and we talk about the same challenges and very often we might leave some scraps on the table of, wow, there would be some cool things we could do together. And so we started to scope out what could that look like if there was a space to collaborate around decentralized trials. Well, the pandemic hit and everybody was heads down, so we put it a little bit on pause in early 2020, but picked it up with a lot of those stakeholders by the end of 2020, and by the end of 2020, we were able to bring the Decentralized Trials and Research Alliance, DTRA, to life, initially with 50 organizations as members, within a year that was over 100, and now I think we have a pretty good steady state at around 130, 140 organizations as members working together to try to address that global challenge of adopting DCT and decentralized research at scale. I spent a fair amount of time on the DCT topic, but it’s not my one and only child. That’s why I enjoy spreading myself around the way I do.

Joseph Kim:
Yeah, so at the end of the day, if you have three hours left in the day and there’s five things to do for five different organizations, one of which is DTRA, do you focus on that? Is that your centerpiece, would you say?

Craig Lipset:
I just find more hours.

Joseph Kim:
Eight days a week, like I said.

Craig Lipset:
Right, I work on things that I’m passionate about, and that’s one of the greatest joys I have for this stage in my career. I’m hardly retired, but I feel like I have this good fortune at this time in my career to choose the people I spend time with, and they’re great people, and the challenges I want to address, and yeah, if I’m working eight days a week and stacking up the hours, it’s because these are challenges I really enjoy with people I really enjoy spending that time with.

Joseph Kim:
So let’s jump into decentralized trials. This has been a very hot topic and on both sides of the spectrum, there are evangelists, there are naysayers, there are charlatans, there are snake oil salesmen, there are the tried and true. It’s a bit of a wild West. And if it were a religion, I don’t want to talk about religion, but if it were a religion, it’s all these different splinters. And I’m a fan of the notion of a DCT for sure. I have no problem with this term. What I have a problem with is that everyone is now using this term to sell their wares. Like when I went to SCOPE earlier in 2022, this was the first like big conference that came back to, and all of a sudden overnight, every single provider was a DCT company and I was like, come on, bro, this has gotten out of hand. So help us understand from your perspective how you really think about a DCT and what is its intention. What’s the whole plot of a DCT?

Craig Lipset:
It’s funny you mentioned SCOPE. It was 2020, January, at SCOPE that I had used this one slide that was meant to show the oversupply of decentralized trials capabilities in the market, and it’s pinned on my Twitter feed, @CraigLipset. The slide just showed the 17-year history of DCT up to that point and how there was so much investment and announcement of capabilities, but really a pittance of adoption, right? It was just little experiments here and there at a handful of companies, nobody doing anything meaningful at scale. And so it is funny to think then two years later, what SCOPE starts to look like. Now, I will say this, that the early folks that have been marketing the heck out of saying that they do DCT, I don’t hold it against them because I don’t know that they’re all charlatans and snake oil salesmen, but what they’ve done is they’ve defined the term in their own image. I do DCT because I have some visiting nurses, I do DCT because I have an\ electronic diary that could be used in the context of a decentralized trial. There are lots of components and tools that are part of a decentralized toolbox of methods and processes that are needed there. Now, there are some that certainly push those limits. There are certainly some that you’ll see say we do end-to-end full-service decentralized trials. And I’ll think to myself, do these folks really even know what it means to try and do a fully decentralized trial, or if the market even wants them to do a fully decentralized? Now, fast forward to where we are today, DTRA has their glossary or harmonizing that with IMI, the Innovative Medicines Initiative, in their trials and homework, and so hopefully we’ll be able to come away with some really well-accepted definitions. Now, does that mean organizations are required to use them? Of course not. Does that mean that people won’t need to embody DCT in their own image, meaning I have these capabilities, so therefore, I will define DCT based on what I offer. They’ll continue to do that, but at least hopefully we’ll be able to contribute to a better market of buyers that are able to better scrutinize and challenge folks when they start to push too far on what they’re offering. What is DCT really? It’s a set of tools and methods, it’s not just technologies, it’s processes that organizations are increasingly committing to. But as I posted on LinkedIn the other day, it’s all about intent of use. If you’re an electronic content solution provider, do you support decentralized trials? Hopefully, but not necessarily. It depends on the how protocol was written. Your paper consent could be more decentralized, if your study process is, we’re going to mail out a paper consent and let people review it and complete it at home, and your e-consent process for that protocol is the patient has to be in the clinic to pick up the tablet and do the e-consent. Which one is decentralized? To me, it’s the piece of paper. So it’s not just about having great technology. It’s how you’re deploying it in a way that gives people choice and flexibility.

Joseph Kim:
I love that. I think that was a great way to help people not wear this badge of DCT artificially and not cast it in their own image, as you said. But let’s get to the other big picture, which is why would anyone try and do, and this is not a dumb question, this is like a rhetorical one, but in your words, why do people want to even embrace these things that allow a decentralized deployment of research? What’s the real big picture here?

Craig Lipset:
I think that from the beginning, most of the factors were patient-facing. And when you look at Cities’ 2018 recommendations from the Clinical Trials Transformation Initiative on decentralized trials, you see mostly patient factors. What could be the impact on recruitment, retention, representation, access, experience? And I think that those factors still are predominant on people’s minds. I think that especially today, where more and more organizations are baking patient insights into their study design and planning process, when you go out and you talk to people in the disease area about their burden of study access and participation, it’s hard to come away and say, I’m not going to do any of these things that aren’t available to me. And that, I think, is the big difference today. Two years ago, three years ago, it was easy for folks to say, these tools sound nice, but they’re not really available to me. They’re not available to me because I don’t know what the regulators think. They’re not available because I don’t think there are good solutions out there. They’re not available because I can’t navigate it through my legal regulatory and compliance people. That’s what’s different today versus 2 or 3 years ago. People can’t say, I can’t do it, these things aren’t available to me. Most large pharma companies at an enterprise level have been spending the last year to figure that out and make them available to you. Now, decentralized method is right for every protocol? Absolutely not. But are there probably 80% of studies where some decentralized methods could be introduced and spare create options for some of the visits? Absolutely. Patient factors will be a driver, as we keep listening to patients, I believe that resilience will be an important additional driver. What sells best in the clinical research industry is not innovation, it’s risk mitigation. And in an unpredictable environment where there’s increasing risk around us. Is it COVID-26? Is it war in Eastern Europe? Is it murder, hornets, fires, or whatever stands in the way? Something will stand in the way of patience in your 24-month study being able to get to a clinic consistently, and how do these decentralized methods start to create some business continuity and resilience for us? I think one of the newer areas for why do this is emerging to be around corporate social responsibility. Most publicly traded companies today have very public commitments around ESG, around environmental, social, and governance, around being able to demonstrate they’re making a positive impact in the environment. And I think as we increasingly are using study design and planning tools that can start to show us how different scenarios have different impacts on the environment, I think that’s going to start to emerge as an interesting additional lever. It’s going to be a yes and after the first two patient factors and business continuity, but I think it’s only going to help.

Joseph Kim:
Yeah, so I love what you said, which was risk mitigation. And one of the earliest, most successful DCT methods was what we called back then centralized rating, right? Early 2000s, to mitigate the risk of inter-rater reliability and psychiatric rating scales. That is, having 50 raters across the country interview patients and score them on the Hamilton Depression scale, whatever, you have three of them that are centralized and then it gets deployed in a decentralized manner because you’re mitigating the risk of inter-rater reliability and rater drift and that sort of thing. And that science actually was so powerful and profound that everyone was like, obviously, this makes a lot of sense. And you got a whole psychiatric community of research to move that way, and I love how …

Craig Lipset:
My early career at Parexel was in the medical imaging business. It was exactly that same narrative that we had developed a competency around the same issue of inter-rater variability in interpreting medical images or other endpoint adjudications. And so just as you’re pointing out, the history of centralizing stuff in clinical research is really long and it’s really positive. We have labs, we have IRB reviews, we have endpoint determination. It’s that centralization that helps to power decentralization. It’s the fact that so much of our competency can be driven in a better-controlled way with centralized resources that can enable then more distributed access. It’s the argument that Clayton Christensen made in the innovator’s prescription around centralization in healthcare enabling minute clinics and these distributed access points.

Joseph Kim:
So we’ve devolved from that really good way of creating a business case and showing that the data proves that this method is better, to today, we’re getting very flimsy or not quite watertight business cases. If you do DCTs, you’re going to save millions of dollars, which isn’t about, then what you’re saying, you’re then focusing the value on like enrollment, which isn’t always the reason to do DCTs as you’ve articulated, it’s not just enrollment. It’s about helping people stay engaged once they’re there, making it more convenient for them to stay, because you may not be able to enroll the entire state of California because you still have to come to the clinic for a specific endpoint or something. So you still have, you haven’t changed the enrollment curve, but you just made it easier for people to stay in, and that’s good enough reason. So what I’m trying to struggle with is, we used to be so good at saying, here’s a method, and here’s why it’s better and the science is unequivocal. So then, like some of these like more looser business cases that aren’t like really kind of saying two different things, like how do you address some of that? How do we tighten that up to …

Craig Lipset:
We have to separate out the scientific and clinical measurements that are a cornerstone for decentralizing versus a lot of the more operational tools that can improve access and experience. The cornerstone for the success of decentralized is to be able to continue to demonstrate patient safety and data integrity. These are our guardrails for all of clinical research. Now, the key enabler for decentralizing will be whether our endpoints can be measured in ways that do not compromise integrity and more flexible locations. That’s why we, centralized imaging and invested all that energy into the inter-rater reliability, that’s why we centralize psychiatric assessments. That hasn’t changed. When we’re looking at decentralizing, the endpoint itself is still paramount. We still need to be able to demonstrate, with the same reliable, robust methods of validation and qualification whether this is a new digital measurement we’re trying to introduce or something otherwise, something, I know you were very committed to in the work at Lilly in your latter years. That is the key enabler here, and we can, there’s no compromise in there, right? If you are mucking around with an endpoint and you’re just going to drop it in a willy-nilly way, you’re destined for failure, and you deserved to be because you’re not investing in the right space. Now, on the flip side, do we need the same level of evidence of impact in using e-consent that we would need in using a digital measurement to replace our six-minute walk test? I’d argue no. I would argue that there are some things that we can believe in, even with a lighter ROI, a lighter level of evidence. We have to have confidence in the quality and integrity of the systems. We should be spending time with patients to make sure it’s something that they want, but that we don’t have to have that same body of ROI that we need for the validation of a new measurement or endpoint. Now that being said, organizations need ROI, right? They’re making an investment, they’re going to continue to make that investment, but every organization that I talk to on the pharma side, the ROI they’re looking for, is a little different and is unique to their own culture and their own priorities. For some organizations, they’re just looking at their existing KPIs and they want to know that we’re continuing to support and enhance existing KPIs. Some are looking more at dollars, but they’re looking at dollars in a much more macro level than just, can I swap the dollars in this one study budget and keep it all cost-neutral? So there’s a lot of different drivers for different orgs and it makes it hard right now. I’m looking forward to the IMS Radio study will be an interesting head-to-head comparison of a group of patients and diabetes that are enrolled to a brick-and-mortar site or to a fully remote study. I think there’ll be some interesting data points that come out from that as far as more operational considerations. But Joe, you lived this life at Lilly, that level of rigor in validating a new endpoint, we can’t possibly bring to every operational tool in decentralized.

Joseph Kim:
Couldn’t agree more. I think, so to your point, something like an e-consent, let’s say, you’re right, we don’t have to create an ROI that shows millions of dollars in savings. The problem is some people think that they need to and then they create these sort of false, not false, but like flimsy, don’t even go there I’d say, just stay in your league. And if you can just prove that it’s better or more acceptable, like it doesn’t always have to be saving millions of dollars because then what happens is you define, not you, people define something as intending to save X amount of money and then you try it and then it doesn’t because the whole thing was built on a, on sand anyway. So I would urge the community to stop trying to over oversell, not literally oversell, but also oversell the impact. It doesn’t have to save trillions of dollars each time. Let’s just be modest and controlled and talk about really what the impact could be, because it doesn’t have to be huge cost savings. And at the same time, I’ll say one more thing, at the same time, at Lilly, we did some surveying of patients and a great many of them didn’t want anyone to ever come to their home, full stop. So this notion of optionality, I think, is equally important as it is as compared to decentralizing things and sending people to the home or making it more quote-unquote convenient, because for a good portion of patients, that’s it’s less convenient, right?

Craig Lipset:
I think there were, I don’t want to point fingers at management consultants again, but some were, I think, overzealous in setting expectations with management and pharma that this is going to be associated with some significant cost savings. And I think when you look at approaches like having optionality and choice like you pointed at, it’s hard for me to say that there is a future that’s going to be substantial cost savings to a study design. If we are going to have futures where I as a patient for visit three can choose between a visiting nurse, going to the clinic, or coming in and having that encounter over video or going to a pharmacy, you’re standing up a tremendous amount of potentially redundant infrastructure that I’m going to choose not to use. And so it’s hard for me to come to the conclusion that DCT done the way patients want us to do it is somehow going to have direct cost savings on your budget. Will that have an indirect cost savings or at least hopefully play out as close to neutral in the aggregate? I do believe that’s the case, but I’m completely with you there, especially with these approaches like you’re describing, with optionality and choice baked in. The only way we’re going to get really good at offering people optionality and choice is if we’re much, a, much smarter and more rational with how much it costs to stand up these options, and b, if we can develop the level of sophistication of predictive analytics that leaders like Amazon have been deploying for years, right? Amazon has a box of coffee waiting to ship to me at a depot somewhere in New Jersey because they know that next week I’m going to run out of coffee and they’re going to ship it to me. Without having that level of predictive power to know which scenario is likely to go down for a particular patient for a visit, we run the risk of having boxes of coffee at every depot in the country just in case somebody orders, rather than having the intelligence to know where we need to deploy our resources.

Joseph Kim:
Yeah, and this level of automation, which is like there’s a predictive analytic and then it automatically fires off the coffee delivery when you hit that threshold for sure. Let’s go back to this risk mitigation thing, because at the scene at Summit, the last thing I said was DCTs are going to be more complex, and that doesn’t mean they’re bad because now you have a whole host of actors that are not under the same chain of command nor within earshot under the same roof. So how do we think about organizing and coordinating those different new organizations into the research ecosystem? It’s very different from people in the same building, all working as a team, 365 days a year.

Craig Lipset:
I think you’re right, especially again, as we’re thinking more about optionality and choice. It’s one thing to say that, that’s fine, I’ll just ask the patient in my app of which one do you want, but what’s supposed to happen downstream of that? If I’m saying now, I’d like to come in for a visit instead of having a home visit, how is that scheduled? How are these different stakeholders coordinated? If I’m now switching and saying, you know what, it’s not convenient for me, it’s close to the holidays now, I’d like there to be a visiting nurse coming to my house? That’s a whole other entity that needs to be coordinated and scheduled, and so there is a layer of complexity there. Now, it will be interesting to see, though, Joe, right, when players like CVS and Walgreens emerge at scale that have visiting nurses and local drop-in spots, will they start to become the more integrated players there? We have in our ecosystem some very large established site networks, often backed by private equity, some of them are investing in their own technology, some of them have invested in their own home health services. Will site networks emerge as the centralized, coordinated ecosystem player? My hunch is maybe, right? I think a lot of them will have some capabilities that check multiple boxes to say, for my patients, I can do home health, for my patients I have my own telehealth or other platform I want to use, but I think we’ll still have this complexity that to make this work across the United States, across the planet, there’s going to be a lot of different players involved that need to be fit together, that need to be on the same page, that need, we need to understand their training and compliance, that we have confidence that they know what to do, and that their checklist manifestos are being presented to them, really.

Joseph Kim:
Yeah, our company, ProofPilot, doesn’t position ourselves as a DCT company, though we do plenty of DCTs, but this is definitely one area where we want to help DCTs be successful to orchestrate and coordinate all those other different players. I’ll give you one anecdote of my experience with DCTs at Lilly. As a champion of them back in 2018, I think, we did a DCT and this was one of those rare moments where you could actually do head-to-head. Much like the remote study, it was in a marketed drug, picking it up from CVS, we had eight brick-and-mortar sites and two DCT sites. I won’t say who the provider was, but much to my chagrin, like the DCT didn’t enroll as much as the brick-and-mortar site. And like you, learned on the remote study for overactive bladder, for our indication, it came down to a little bit more of a HCP patient relationship that made that enrollment happen much faster versus an unknown investigator trying to enroll the state of California. Now, the good news is the study went off without a hitch, there was no error, so it was done with quality, but it just didn’t return that ROI that we thought it was going to. Now, in a different indication, would it? Maybe. Migraine? Maybe, but for this one, it just didn’t. So the one thing I learned was it’s not for everyone. It makes total sense for certain things, and done right, you can, the data quality can be just as high. We check that box, so I’d love to hear.

Craig Lipset:
There’s so much we’re still learning here, right? Remember the Science 37 Roche work in Pemphigus Vulgaris, where at one point their central site was outperforming by 7x their brick-and-mortar sites. And you think, pemphigus, that’s not a very common one. That’s hardly like just a traditional basic, easy, easy derm indication. So it is interesting to me the different approaches and where they seem to work well and where they don’t. But I’ll tell you my, when we did that first remote study, the head of commercial development at Pfizer was a guy named Michael Williams, and he had stopped me in the hallway one day and he had said, this whole like remote trial is going to create a new way for us to engage physicians in the community. And I said, go on, what does that mean? And he went on to say that, today for clinical research, we give doctors in the community two choices, refer your patients to an investigator or be an investigator. And we know those are pretty weak offers that we lay out for most doctors. My wife’s a family physician. She’s never sent a patient to be in a trial, she’s never been an investigator in a clinical trial. And she’s perfectly happy with the world that way, right? If she’s going to do a referral for a patient, she’s going to refer them to a specialist, she’s not going to look and see, is that specialist running a clinical trial that’s right for this patient? No, she’s going to refer them to a specialist that she knows and that she trusts. Then it’s serendipity. Is that specialist in a … trial? Statistically, they’re probably not. And are they then going to refer a patient to another specialist in their field? Egotistically, they’re probably not. Why would they? They’re a gastroenterologist and nephrologist, they treat people in that indication. Now, what Michael was pointing to, though, was how will this whole decentralized movement, even back then, he saw it, create opportunities for that physician, my wife, to have a different role to play in a trial without giving up her patients and bleeding patients from her practice and without the burden of becoming an investigator, and I think we’re starting to see that, which to me is perhaps the most exciting part of this story that’s still yet to be told. How do we enable treating physicians in the community to have new role in research that we haven’t been able to offer them before? Don’t be on a 1572, don’t be a … It is not right for everybody, but how do we help you to open up research access for your patients without it looking like it’s, we’re just there to bleed patients out of your practice? Decentralization, maybe dropping video into their practice, maybe that sense that they’re not losing the patient in the process. I think is a great story that we’re really just at the beginning of.

Joseph Kim:
Or even having a patient being able to self-integrate their EMR record from a physical exam and push it over to the investigative site, you’ve indirectly have involved an HCP in that way. And we, of course, we do this responsibly, but I agree with you, there’s a whole bunch of other opportunities there.

Craig Lipset:
Because these people that we’re looking to enroll in trials aren’t medical mysteries. They have a diagnosis, they have a prescription in most cases to be eligible for our trial, which means they have a doctor in their life. And in most cases, our clinical trial is suggesting to them, did your doctor come into my trial? I think that’s a dish that’s best served by going to the source, the person that patient’s already trusting, their doctor in the community. How can we better engage my wife to be able to stimulate referrals into trials? That, by the way, is when I will retire from the industry. When I get my wife to start making referrals into trials, I’ll say my job is done.

Joseph Kim:
Hopefully not too soon, right? We want you around. So last question here. Make a prediction that you hope comes true.

Craig Lipset:
I think that we will start to see some signals of guidance from at least one major regulatory authority on the planet that starts to demystify the expectations of decentralized in that region. And by the time we are at this point where we are recording this right now, we’ll start to see even more of that from other agencies. These will be really important examples to help stabilize this space, we’ll start to see greater harmonization around our language as well, which hopefully organizations will embrace, but we can’t guarantee that. And then I think the DTRA annual meeting, one of my favorite blocks of time, was having folks from Pfizer, BMSBI, Otsuka, each come to the stage and share how they’re normalizing DCT in their organizations, and really looking forward to seeing even more of those stories, because this is what people need to see. It’s, there’s hype and there’s rhetoric and there’s lots of articles preaching the future of virtual trials, but seeing organizations really normalizing and stabilizing, that’s what we really need to see in this space.

Joseph Kim:
Yeah, fantastic. So guidance from a regulator, a couple of real stories from pharma companies doing it. I hope to put …

Craig Lipset:
Continuing to lead.

Joseph Kim:
In the Bruins.

Craig Lipset:
That’s right.

Joseph Kim:
We hope to be part of that conversation. We’re spinning up a couple of DCTs right now, so when there’s something to tell, we’d be happy to tell it to help put wind in that sail as well.

Craig Lipset:
Outstanding, outstanding. I really appreciate this opportunity, Joe. I love how you’re continuing to use your voice as you’ve done so well in your past lives at Lilly and before, and continuing to make sure that good stories and truthiness prevails out there.

Joseph Kim:
Listen, kudos to you for always being on the forefront in the vanguard of a lot of these things. It’s been great watching you, working with you, and interviewing you today. Thanks so much for joining us and have a great day, Craig.

Craig Lipset:
You too, thanks again.

Joseph Kim:
Thanks.

Joseph Kim:
Thank you for tuning into Research Confidential. We hope you enjoyed today’s episode. For more information about us, show notes, transcripts, and resources, please visit ProofPilot.com. If you’d like to debunk a clinical research myth, share some war stories, or maybe just show our audience what kind of heroics it takes to pull off gold-standard research, send us your thoughts, episode ideas, and more to help@ProofPilot.com. This show was presented by ProofPilot and is powered by Outcomes Rocket.

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