Andrew Brackin: [00:00:00] I’m Andrew Bracken and this is First in Human. Vial is a CRO that empowers biotech with faster and more efficient clinical trials. Today, we’re talking about decentralized trials with Craig Lipset of DTRA. Hi Craig, How are you doing?
Craig Lipset: Hey, Andrew. It’s great to be here. Thanks for having me today.
Andrew Brackin: And, DTRA is the Decentralized Trials…
Craig Lipset: …Decentralized Trials and Research Alliance. DTRA. It’s a global collaboration with about a hundred organizations from pharma and biotech, CROs, tech companies, government agencies, site networks, and advocacy groups working together to ease the global adoption of decentralized research. And, I have a feeling we’ll have a few minutes together to talk about what exactly that even means.
Andrew Brackin: Exactly. I’d love to know more about your background and how you got here.
Craig Lipset: I have a couple of decades in clinical research. Recently, I went from a tech and services background to biotech to pharma. I was the head of clinical innovation at Pfizer, leading innovative work in their development organization for about a dozen years. During that time, I had the opportunity to help design and lead the industries first fully decentralized clinical trial.
I’ve been independent for the last four years. I split my time as an educator, teaching in health informatics and clinical trial innovation at Rutgers University, as an advisor with a number of pharma tech and investors, as an advocate with groups like the Foundation for Sarcoidosis Research, and as a board member with groups like the Decentralized Trials Research Alliance and others. All of my energy is focused still on the same problem, on the same use case. How do we identify and scale, smart and innovative opportunities to impact clinical trials and medicine development? I just tackle it from a lot of different angles at the same time.
Andrew Brackin: That makes a lot of sense. Why don’t we start at the beginning. Can you explain to us what is a decentralized trial and how does it differ from traditional trials?
Craig Lipset: That’s a great starting place. When people hear decentralized trials their minds may jump in a lot of different directions. To keep things simple, let’s go with its definition. A decentralized trial is one that leverages technology and or processes that can help enable visits to take place outside of a traditional research site. If you break down those words that I just used, this is a story about certain technologies, like electronic consent, self-reporting, connected devices, digital measurements, use of video.
But equally important, can be the use of innovative processes, extending our drug supply for people at home, using visiting nurses and home health services, maybe configuring our research sites themselves to service central virtual sites. Importantly, I didn’t say that everything takes place in the home or everything has to take place one way or the other. This is about, ideally, creating pathways that can give people more choice and options in how to participate in access research.
Finally, that last part outside of a traditional research site. Because those visits could take place at a site, they could take place at home but, increasingly, we’re seeing more expansive locations for where research can take place. This all fits in that overarching theme of how do we open more doors for more people to be able to participate?
Andrew Brackin: The hybrid model is just incredibly interesting. When you think about some of the visits that happen in the clinic today, it feels like so many of them could be hybrid remote visits. We’re obviously doing this interview remotely, and it feels like the ability to put more remote visits into trials will allow for far more flexibility for patients, increase retention, and solve all these other underlying problems that we have when we run trials.
Craig Lipset: Hybrid just makes sense, right? It’s how we are operating our lives as businesses. We still have meetings and conferences, but we can operate remote and virtually. It’s how we do our grocery shopping and order dinner versus go to a restaurant. I don’t want my supermarket or restaurants to close their doors to me. I still want to show up once in a while, but sometimes I need other ways to access them.
When we look at ratings of experience at research sites around the world, they’re overwhelmingly positive. Our challenge in clinical trials is not that people don’t like their experience with sites. The challenge is they can’t always get there. The opportunity isn’t: let’s shut down sites and replace them with entirely virtual models. There may be some types of studies where that’s fully virtual approach could make sense. But, for most people, when we talk to people and listen to patients and different indications around the world what we hear is pretty consistent. I’d like to be able to get to a site when I can, but I’d like other options to be able to access, just to be able to fit with the other burdens and challenges in my journey as a patient and in my [00:05:00] life as a human.
Andrew Brackin: Do you think that some of the decentralized and virtual trial vendors are building for a world of a hundred percent or most of the trials that they support being virtual and decentralized? Whereas the traditional software vendors aren’t really adopting or implementing software that would allow for greater decentralized trials. It almost feels like there could be a bit of a disconnect today, and maybe Vial should solve this gap eventually where you could support more of that hybrid model where certain visits are in person and then others are virtual.
Craig Lipset: The universe of tech and service providers supporting this decentralized category are extremely diverse in the approaches and strategies they’re taking. Some are definitely creating tools that can be used at this site or it can be used from home. But, we still see hybrid in most implements as being ones where our protocol is dictating that visit one shall be in the clinic, visit two shall be with a visiting nurse, and so on.
It’s hard for us to truly embody what a study with choice and optionality looks like. One where we’ve scrutinized every visit and every schedule and we’re creating every possible opening for every doorway for each of those visits. One of the reasons that’s hard is just the cost and the logistics of operating in that environment, how do I have a visiting nurse on standby? And an investigator ready on the video screen and the study coordinator ready to receive someone at the clinic, just waiting for them click a button and make a choice. Do they have to click that button and choose a month in advance for me to manage the logistics, or, can they do it within a few days?
It’s certainly much easier in my local restaurant, because we can leverage certain shared infrastructure. A DoorDash driver could deliver for my Chinese food or my pizza and is pretty agnostic. Because our studies are so granular and specific. It’s harder for us to leverage shared infrastructure like that. It makes it much harder for us to operationalize some of these approaches today. We also are still hungry for next generation predictive analytics that can help us to anticipate what a different patient may want or need for their next visit so that I’m not sitting three different scenarios always ready on standby.
Instead, how can I use more data to predict and anticipate that this patient is going to want a video visit or a home visit? Amazon does this with all of us as consumers every day. They know that I’m gonna order batteries tomorrow and have some batteries waiting at the depot closest to me, ready to go. How do we bring that same type of savvy around prediction and bring more of that into better managing experience for patients in our trials?
Andrew Brackin: How has the pandemic and Covid 19 impacted the adoption of decentralized trials? It seems like the COVID 19 trials, themselves, although Covid 19 may have increased adoption, did not really use any decentralized visits, as far as I’m aware.
Craig Lipset: The pandemic catalyzed a spike in the adoption of approaches that were already available for us. We didn’t have to go back to the bench and start coding and creating tools to help decentralize our trials. They were already there. What we found was the prior to the pandemic, operators perceived these approaches as bringing risk. During the pandemic, there was other risk in the environment that outweighed the risk of adopting these approaches. The risk that I’ll miss patients, lose patients, lose data points in my trial outweighed the risk of whether I could successfully implement video, whether I could successfully implement a home visit in a trial.
It was a question, always in our industry, of risk benefit and with adding in the additional environmental risk we adopted. The interesting question will be what happens as this pandemic recedes, becomes endemic in terms of adoption curves? I think that we will certainly expect to see some hesitancy come into the environment when there’s uncertainty around how regulators will percieve these approaches going forward.
We’ve already seen papers coming out with decisions from EMA, China, Japan, Taiwan, other markets. We have guidance that’s on the horizon very soon from the FDA, all around decentralized trial adoption. As we remove that ambiguity, I think we’ll continue see that upward trend in the use of these tools. Because as operators, we now know how to use them. When we take increased operating confidence and regulatory ambiguity, then we can see that type of adoption continue.
Andrew Brackin: Let’s talk about the drawbacks and challenges associated with decentralized trials. We’ve talked about a lot of the benefits. What do you think companies are struggling with from your perspective?
Craig Lipset: When you think about that risk benefit story, the patient factors ideally in terms of improving access experience. Ideally being supportive of our goals of representation. During the pandemic, this [00:10:00] was really a story about resilience and business continuity. Why did the White House Office of Science and Technology policy put out an RFI about emergency clinical trials? Some of it was to see how do we stand up more of these approaches for continuity of research in an unpredictable environment? In between war and pandemic and other concerns that will stand in the way. There will always be some environmental factor that places a patient in jeopardy of not being able to get to a site. Increasingly now, Andrew, we see a third factor even beyond the patient factors in business continuity. We see, primarily coming out of Europe, a focus on green trials and sustainability efforts.
As organizations, both large public and private biotech, focus on ESG and corporate social responsibility. Certainly the large public pharma, but the small biotech, because their investors, the different funds involved, want to show their supporters that they’re placing smart bets in these spaces. How can decentralized help us in terms of quantifying a better impact, a better footprint, less burden to the planet. But to your point, there are definitely downsides and risks, here.
We can’t throw unfamiliar technology at patients and at sites and expect this to just work. People don’t want to be left at home with an unfamiliar gadget and a box of investigational medicine. That’s daunting. And, so making sure we have robust tools, tech, processes, and support in place. You hinted earlier about enthusiasm waiting for the FDA guidance. We’ll get some clues when we open the EMA’s recommendations on decentralized that speaks extensively about the importance of investigator oversight in these trials.
When we think about drawbacks and challenges, that’s certainly one of them. How do we make sure that our investigators have the data and tools that they need if there’s a visiting nurse going out, if there’s a connected device that has data flowing over to the right, and some other contracted visiting nurse providing some support over to the left?
How does all this data and intelligence come back to the investigator, so they can do their job in terms of oversight and safety? Finally, making sure we have important considerations embraced around our endpoints and our measurements. For many organizations there are great investments taking place to digitize, and modernize measurements and end points. That certainly helps us to create more flexibility around location. How do we have confidence that the way we’re measuring it at home is the same as the way we’re measuring it in the clinic? When we have a digital measurement, we get more objectivity and reproducibility agnostic to location. But these are some of the challenges we have to consider when we’re planning.
Andrew Brackin: The endpoint question is a challenge across the industry, right? Looking at certain areas of medicine where some of these more subjective endpoints are being questioned. Not just in decentralized trials, but in all trials we’re looking for better endpoints. That would be a great benefit. All that technology will create a lot of value across the spectrum.
Craig Lipset: So many organizations have different initiatives happening in place. I know a lot of Vial’s community is emerging biotech companies. But just for them to be cognizant of: how do I leverage these? When you look at the non-drug initiatives in the development organization in pharma, you see over here about real world data. Over here, about digital measurements. Over there, about decentralized. Over there, about AI and predictive. Over there, about DNI. How do other organizations, in particular small and mid-size biotech, be able to take advantage of what is coming from a lot of that work, even if they don’t have resources to run half a dozen initiatives like a Pfizer and a Novartis might.
Andrew Brackin: How do biotechs, should they engage with the DTRA and if there are any biotechs listening that, are considering using some decentralized strategies in their trials, how should they work with you?
Craig Lipset: It is funny you mentioned that. We have this year a new program reaching out to biotech leaders. I wasn’t even planning on bringing that up here today, it is that new. But, if you are a leader in biotech, we are making room for you in DTRA. So much of our community are the larger pharma and biotech that have been investing in this area. We realize that CMO, that head of R&D at that emerging biotech or mid-size needs to understand what is reality, what is actually capable of happening today? What are the regulators really supporting?
So within DTRA, something that we’ve introduced this year are these micro communities. We have a community of DCT leaders in pharma. We have functional communities for different folks that may be leading in monitoring or data management in these areas. And we’re looking to bring together a similar community for leaders in biotech that have their own issues, concerns, considerations, and needs, and how we can bring those [00:15:00] stakeholders together. I would encourage folks to take a look at dtra.org. If you are from biotech and you’re interested, there’s a form to fill out and an email address: secretariat@dtra.org. We’d be happy to follow up there. It’s an exciting opportunity that, before this year, we weren’t well positioned to support.
Andrew Brackin: That’s exciting. We have a number of listeners who will be looking up your website and doing a lot of research after this interview. I want to close out with a question about equality and equity in clinical trials. Diversity in clinical trials is obviously one of the top priorities of the FDA. They’ve made very clear that any drug that will be approved in for the foreseeable future, they’ll be looking at the diversity of the patient population and making sure that it’s representative of society and of the real patient population for that indication. How do we ensure that decentralized trials are accessible and equitable for all patients considering the technology requirement that we spoke about earlier and the learning curve involved?
Craig Lipset: When we think about the technology involved with any of the tech in our studies, we can’t assume that people have access to either certain devices or certain bandwidth and connectivity in their homes in order to support participation. Even as our industry has made a very important step towards BYOD and enabling people to use their own devices in our trials, we still need to anticipate provisioning, technology, or connectivity for those who don’t have in order to make sure that this is a level playing field.
As organizations are developing their diversity action plans, I hope that none of them are putting the word decentralized trials at the top of the list, checking the box, and then flipping the page to work on another challenge. Decentralizing is a great companion for your diversity plan. It is not a solution for diversity in our trials. We have to address important top of the funnel concerns, in terms of earning trust and making sure that people feel that they’re invited to participate.
Once people are being engaged and to even consider a trial, because there is trust and awareness and that invitation has been extended, decentralized then can help in terms of making that trial more accessible. Help that person when they’re moving through that decision funnel and considering a trial, as far as whether or not it’s right for them and then in terms of their participation. The decentralized can be a part of your diversity plan. It shouldn’t be the first box on your plan. It should never be a place where we check that DCT box and feel diversity is now baked within. It’s a great companion for improving access.
Andrew Brackin: Thanks so much Craig. I appreciate the time today. It was great to learn about decentralized trials and the opportunity ahead of us.
Craig Lipset: I appreciate the opportunity to join you here, Andrew. Thanks, again.
