What Is The Future For Research Sites? - Craig Lipset

This week, I'm joined by Craig Lipsett, advisor and founder at

clinical research partners. And I'm pleased to say the newest member of tecno's board, a former head of innovation at Pfizer. Craig is at the forefront of innovation in clinical research and medicine, development, bringing vision and most importantly, action at the intersection of research, digital solutions and patient engagement. During this episode, Craig talks about decentralized trials, elaborating on how they are changing, how we think about what a site is, especially in the post-covid era, and explains how tech CRO can help to support this transition.

Welcome to the podcast, Craig. Great to have you here. Now, while I think many listeners will be familiar with you, could you start by explaining more about your background? So I was at Pfizer, as you mentioned in that intro for about a dozen years, including time as head of clinical innovation.

But today I split my time in a few different directions. I do work as an advisor and board member with a number of organizations, both for profit nonprofit, both technology and service providers, but also pharma and research sites. I work as an educator. I am

on the faculty as an adjunct assistant professor at Rutgers University.

And health informatics. I continue to work as an innovator and help a number of very young startups come to life to try to make their impact in the field. And I'm an advocate. I serve as a board member for the foundation for sarcoidosis research, where I serve as vice president on their scientific advisory board, but also as a patient myself.

So I am splitting my time in a number of different directions, but they're all surrounding the same challenge. How do we identify and scale innovative new opportunities to impact clinical trials and medicine development? What may not be a well-known fact is that you are on Ted Cruz board. What are you hoping to accomplish as a board member?

Well, as I mentioned a moment ago, I have this opportunity today to split my time across a number of different stakeholders in our ecosystem, working with pharma, with tech service providers and sites as well as investors. And it gives me a lot of great visibility to the different challenges and opportunities that are out there. I am passionate about bringing that into organizations

that are growing and help them to make that impact that they hope to realize. Certainly with tech row, that opportunity is there, both in terms of where the company is and its state of growth, but also the talent that exists from the board straight through the organization.

The existing product is so well regarded, it just seems like a wonderful seed to continue to grow itself and also look for other adjacent areas that can help complement this ability to improve operations at the research site. There's a lot of hype around decentralized trials. COVID 19 triggered a lot of changes, and we're seeing a long term industry shift towards decentralized or at least hybrid trials. What aspects do you believe will stick or not stick post-pandemic?

That is a great question and it is the big question right now. Certainly decentralized trials weren't new. They existed prior to the pandemic. In fact, in January, just before the COVID lockdowns, I had presented a slide on the 17 year history of decentralized trials at the scope summit just a few months before things started locking down.

Now, my theme for that slide was we had an oversupply in the market. Given all of the investment, given all the capabilities being announced, we really didn't see widespread adoption. We saw a number of pharma that had interesting experiments at best. Now, during the pandemic, certainly we needed resilience.

We needed countermeasures in this unpredictable environment to make sure that patients could still access investigational product safety, could still be monitored, efficacy data could still be collected, and a host of other concerns at the site level and the clinical operations level and decentralized research methods just made a lot of sense, being able to introduce opportunities for video and remote visits, using whether visiting nurses or other innovative approaches. And so today we see organizations that have made changes to their SOPs and training, they've made changes to their protocol templates.

They have identified new types of partners and vendors that can help fill gaps. And they're systematically reviewing their protocols to look at where there are visits in the schedule that can be enhanced or supported by offering patients more choice and flexibility. Now there is a DCT 1.0 that is being widely embedded by many, if not most of the top pharma today, whether that's including electronic informed consent and/or use of electronic diaries or other types of opportunities for remote monitoring or services such as visiting nurses, and our ability to extend the supply chain for patients in the home.

Many of these are commitments that are already established in many organizations. There's also a

wide number of what I would think of as almost 2.0 opportunities that companies are experimenting with today, whether they're mobile or pop up sites and a range of other opportunities. So I think that when we look beyond the pandemic, this willingness to challenge the assumption that a patient has to come in for every visit will outlast COVID 19 and the appreciation that regulators are receptive to innovation.

They are friendly and receptive to having new approaches introduced that can support high quality data while offering patients more choice and flexibility. You mentioned that effectively decentralized trials are changing the way we think about sites rather than them being in one physical location like a hospital or a clinic. Clinical trials can be more local, a doctor, office, lab, et cetera. What challenges do you believe this will pose?

Our challenges for clinical trials remain the same whether the patient is coming into the clinic for every visit or staying at home for a visit or any permutation in between. We have to ensure patient safety. And we have to have confidence in being able to demonstrate data quality and integrity. Those are no different.

When we're starting to unlock other locations where a patient visit can take place, we still have to have confidence in our data flow and that does get more complicated when the data is being collected potentially in different locations. And we have to have confidence in the safety measures that we have deployed for monitoring our patients. Now, fortunately, most decentralized trials today are able to take advantage of a number of different remote monitoring technologies, specimen collection technologies, and otherwise that give us a much, much greater sense of flexibility in how we can monitor safety and how we can do so in ways that are not compromising data supply chain, data flow, data integrity.

But we still have challenges. We have challenges today for sites around topics like the complexity of various technologies that are being deployed. Sites have always been trapped in this space of having to use. So many different technologies on a study by study basis.

That's only becoming an even more complex web in this world of decentralized the way we're implementing today. We also have a challenge around investigator oversight and helping investigators to ensure that they are able to fulfill their obligations in terms of serving as the GCP trained investigator for the trial. So what do I mean by that? As we're introducing more and more different stakeholders around the site, stakeholders that can

improve access and convenience for patients?

How do we, as sponsors and Cros, make sure we're continuing to fill our commitments and obligations around oversight? And we're not separating the investigator from the patient through intermediaries. That removes the investigators ability to perform their function as the central party responsible for patient safety. So we have challenges.

Some have become more complex because of decentralization, but I also think we're still in the early days around how we're implementing, and I suspect we'll see quite a few new models still evolving in this space. So if we think about tech Roe's role in plugging these communication gaps, if we think about decentralized trials and all the different parties involved, there's a huge opportunity to help with protocol, compliance and even patient retention. Can you explain more about this? You know, as we were mentioning a moment ago, the universe around the investigator patient relationship is growing and it's growing more complex.

There are new stakeholders that are being introduced and getting involved in the process, whether that may be visiting nurses or retail pharmacy, whether that may be mobile pop up research units in the community. Maybe it's around our ability to acquire cat scans, imaging and specimens closer to the patient's home that may be supported by central labs or even ways to include and engage the treating physician in New ways. And a new roles. All of these layers surrounding the investigator add new stakeholders, and these new stakeholders need to be aware and informed of what is needed in the study.

They may not have traditional roles going forward. As just investigator and coordinator, we need to make sure that all of these stakeholders know what they need to know. Even despite the complexity of being involved in these trials that have lots of different support systems to improve access and convenience for patients, you know, while on the one hand, everything I just described can seem like a question of, well, why would we introduce such burden? But I often like to remind folks that burden in a lot of ways is it's like matter.

It can be neither created nor destroyed. We just move it around. And so this burden always existed in the trial. It was just a burden that we push on to the patient or the study participant.

They had to come in for every procedure, every visit, every blood draw. Now we're creating more access and convenience. Some of that burden gets shifted around. And the question is, who's going to be there to absorb it?

We can't push it all onto the site. There are already as a stressed environment in terms of capacity. And so I think as our systems here get better and smarter, are we pushing that on to other third parties? So is it going to land on cross on sponsors, on tech partners?

We'll see. But while it may seem to some that decentralized feels like a place where we're just adding burden, remember, that burden was already there. We're just trying to take it away from the patient. We talk about the fact that there aren't enough investors involved.

In clinical research. And unless we get more referrals, there aren't enough patients to participate in clinical trials.

How do you see doctors changing either patient or physician engagement in clinical trials? When I was at Pfizer and we were designing and starting to execute that first remote trial, one of the first fully decentralized trials with a product under an FDA phase Ii.

And I remember this distinct hallway conversation with our vice president of commercial development, and he stopped me in the hall, and he shared his reflection that if this model worked, we would be creating a new way to engage with treating physicians in the community. And that led to a conversation where we were talking about the options that we provide for physicians today. In today's world, we either, a, invite a physician to become an investigator in a trial, or, b, we ask that physician to refer their patient to be in a trial. Neither of these options are really fulfilling for the overwhelming majority of physicians in the community.

I think about my wife and who's probably seeing patients in our dining room on video right now. She's never been an investigator in a clinical trial. She's a family physician here in New Jersey. She's never been an investigator and she's not

interested in sending her patients away.

If if our models for equity in clinical research are dependent on physicians being investigators, then we have a broken system because we can't expect every physician in every country to be an investigator in every trial just to help ensure their patients have access to that study. And now, likewise, stimulating referrals is something of a unicorn. We talk about it a lot, maybe from a recruitment strategy. We provide the site some template letters.

They can send out to physicians in the community. But remember, in markets like the United states, physicians operate on a fee for service basis. They generate revenue to feed their families and support their practices by seeing patients. And if they're simply taking that patient and sending them away to be in someone else's practice, creating leakage to their practice, to their business, that's undesirable.

You know, when I think about the state with my wife as an example, as a primary care doc here in the u.s., if there is a patient who might be eligible for a study, she's not going to look for a study to send them into. She's going to refer them to a specialist. And that specialist is not going to be chosen by her based on whether they are an investigator in a particular study.

She's going to send that patient to a specialist that she knows and trusts. And from then we have this same challenge serendipity. If the patient is seeing a doctor who happens to be an investigator in a trial, that happens to be right for them, great. Maybe they'll learn about the study.

But short of that slim chance now, if decentralized can let us enable a visit to take place at home or in a pharmacy, how can decentralized enable us to host those study visits inside the offices of treating physician and the community? And just like the patient's home is none a 1572 in the US marking it as a site. Well, how do we think of the doctor's office and the community in the same way? Having investigators supporting visits by video can start to enable new ways for us to unlock that new role for physicians in the community that head of commercial development stopped me in the hallway about years ago when we can enable patients to be seen consistently by video.

How does that or with the support of visiting nurses, how does that let the physician in the community no longer feel threatened by a referral? They don't have to send their patients away. They can keep them and offer research as a new option within their practice without necessarily having to be an investigator or an investigator in every single study. In

order for that to happen, I'm really excited to see these new types of models unlock.

Some of them are going to be really nice consequences of the increased adoption of video and visiting nurses and other decentralized research methods to enable the vast majority of physicians to have a way to engage in research that they've never had before. Yeah, if that happens, that would be a real game changer. Now, if we move to the topic of diversity, equality and inclusion, how do you believe that? It's addressed challenges around these industry goals.

Diversity, equity and inclusion have so many different sources in terms of why they represent a challenge for study participation in different countries. Some of the reasons for why there may be a lack of representation in a trial could simply be due to physical access, that the sites are just too distant, that they require time off from work and therefore marginalized those who may not be of sufficient employment, that they can just have flexible time. If you're salaried and taking time off from work in order to travel across town for a study visit, you're losing money. And so some of the challenges for some may just be around access.

In other cases, though, so much of the challenge around diversity and inclusion is around trust, and DCT alone doesn't solve trust. As we were talking about, decentralization can help in terms of enabling ways for your local trusted physician in the community to participate. Maybe we'll start to see more mobile and pop up sites align and affiliate themselves closely with embedded, trusted entities in diverse communities, whether churches or other locations that people in the community already know and trust. But importantly, there was a line I remember hearing from an advocate back when we were planning the Precision Medicine Initiative in the US at the National Institutes of Health.

The line that they shared was, you have to stop talking about building bridges into diverse communities and instead shift your thinking to building bridges out of diverse communities. And what they meant was just showing up in the community with a bunch of white people and white coats isn't going to earn you trust. That's not going to be a solution. Building the bridge in from where you're

sitting.

How do we begin? By engaging in communities, listening to people around their challenges and helping to build the bridges out. I know that may seem like semantics, but it does mean a mindset shift in terms of how we think about using some of the different decentralized research methods and ways they can truly make them work. Maybe we shouldn't just be building a bridge in and trying to pop up one of our sites, but building a bridge out by listening in the community, identifying where there is trust, building that bridge it out, maybe using some of those same tools, video or a mobile unit or what have you.

But it's a mindset shift in terms of how you design it to begin with,

listening and earning that trust. So my long story short around this is decentralized can be a great enabler to support diversity initiatives for patients where physical access, geographic distance or the barriers in and of itself could be a solution. But where we're really trying to overcome long standing issues around trust, decentralized can be a great tool that needs to be a part of a much larger toolbox that can make true and meaningful change in how people view research and access it across all different communities and in the different countries we're trying to touch.

Let's look to the future. How do you envisage a typical site operating in five years and at what point do you think DCT or probably more hybrid trials become standard operating rather than something shiny and new? Well, I guess my answer will be twofold here. On the one hand, I could say that sponsors are embedding this and there are processes.

You have some sponsors that have modify the template language in their protocols to include these methods systematically. And so as we see those types of changes in training, sops, template language, the idea that these are no longer shiny and new but become embedded is a pretty good path. But as I mentioned, our current models are creating significant stress and burden on the research site staff. And so as I think about the coming five years, I do expect there will be some shifts in what decentralized starts to look like.

I think that we can expect to see certainly this continuing trend about trying to offer patients choice and flexibility on a visit by visit basis. More and more sponsors are scrutinizing their protocols along those lines. Exactly reviewing that schedule of events and trying to identify all of the ways in which a visit could take place. But the place where we need to see some transformation over the coming

five years is to shift the mindset of sponsors and cross the mindset that to maintain control in my trial, I need to push study specific technology down on the research side.

Sponsors and zeros have done this for years myopically because of the perception that improves quality. If all of my sites are using the same tools for all of my patient visits, I'll have more consistency, more quality, more confidence in my data flow and integrity. Of course, any site would laugh at that notion because they're being thrust upon with so many different technologies and tools for every study that they're touching in their portfolio. There's no way for them to use those in a consistent way of quality and ensuring integrity, rather.

The question going forward needs to become what technologies and tools is the site using? How do we have confidence in the minimum quality standards of that technology? How do we backfill and supplement them with technologies only when needed? And how do we as operators on the sponsor and 0 side focus not on pushing unfamiliar tech but focus on interoperability?

To me, a great example is electronic. Informed consent and consent can be a great resource for so many reasons. If you are a research site that is spending half of your time running a government funded or investigator initiated research, there are tools you're probably already using for your own practice. If you're a large academic center, maybe in the United states, you're probably using something like REDCap.

And so for half of your studies, you're using an open source platform like that. And then for the other half of your studies that are sponsored research with phrma, you're getting a dozen, two dozen different other consent solutions going forward. How can we let the site use the technology with which they're already familiar and focus on minimum quality standards? So how do we define to say if a site is using technology X that's acceptable and on interoperability that matters?

So in that case of consent, what do we really need as sponsors, signatures, dates and versions? If there is another way to capture the consent information, that is easier for the site, we should let the site use it. We should be focusing on data flow, data integrity, and making sure that the site is able to capture that in ways that work best for them. It's early days for those types of conversations, but as we start to think about product roadmap and as we start to see voices of site get louder and more clear, I do have optimism that we are going to start down this type of journey over the coming years.

Will that be a site model in five years or ten? I'm not sure, but I do have confidence that will become a significant part of the future and hopefully improve quality in the process. Because when sites are able to use tech on which they're already trained, familiar and using every day will have less training errors, less retraining needed people will just use the systems they already know. So I just wanted to go back to.

Question one. And I think you mentioned mainly what will stick. And I'm wondering if you could specifically address what you don't think will stick. One of the things that won't stick, I believe, is this chaos of lots of fragmented, disconnected tools and services that are getting thrust upon sites and other stakeholders.

I think something else that will not be sustainable is to maintain this ambiguity of different services that pharma are contracting with directly, that are wrapping around a site and expecting the sites to sign delegations of authority, that they'll continue to be able to do their work, even with these other foreign stakeholders, unknown to them contracted by the sponsor, kind of being pushed around them. I think some of those models, quite honestly, are just not sustainable. On a closing note, I would say the thing of stickiness that has a risk of not sticking that we all need to find ways to make sure it sticks.

Is this receptive mindset that so many of us embraced over the last two or three years? I won't say that you have to embrace decentralized. You have to embrace risk based monitoring. You should be looking closely at these in your organization.

But if I had one wish for what would stick coming out of the tragedy of the COVID 19 pandemic, it would be the receptivity that people have shown to try in a thoughtful way, to take calculated risk and introduce new approaches, new countermeasures, new strategies in our studies. This spirit of thoughtful risk taking in whatever area we operate, managing and mitigating risk while also being able to embrace the new. If there's one thing that sticks coming out of the pandemic for all of us, I hope it's this.