Transforming Clinical Trials: How Digital Endpoints Are Leading the Way

Okay, thanks. Well, hello ladies. This is the first time that Cut the Chat has actually had two participants and individuals that I'm interviewing. So welcome, Lauren, welcome Victoria. It is such a pleasure to have you both here today, and I am thrilled to be talking about this fantastic project around digital endpoints, the talk of the season, right? So we're excited to dive into this and to really hear your thoughts. We're going to cover some of the basics and then get into some details. Victoria, I'd love to start with you. Could you share with the listeners why this project, what you're looking to achieve, and some of your decision-making around choosing your partners?

Yeah, thank you so much, Sabine. And first, I just want to say it's so great to be here with all of you. The project that we're working on as part of the Digital Medicine Society's pre-competitive collaboration is focused on making the business case for using digital endpoints in clinical trials. First of all, DiMe is a research organization that is focused on moving the field of digital medicine forward. And as we all know, so much effort goes into the development of digital health technologies, and there's also a lot of promise and benefit in using digital endpoints in clinical research. But what we've seen is that their adoption has been quite slow, and the goal of this project really comes down to increasing adoption of digital endpoints in clinical trials. We hope to do that by showing their value, by being able to demonstrate the business case for using digital endpoints in clinical trials. And what DiMe does so well is develop open-source resources that are user-friendly, easy to use, and effective.
Ultimately, what we hope to come out of this project is providing some of these resources that teams within sponsor organizations and tech organizations can use to actually make the business case for why digital endpoints should be used in trials. And you bring up a good point about our partners — we've got a very diverse group of almost 40 organizations working with us on this project. It includes sponsor organizations, as well as the med tech companies that are actually developing the technologies, and some academics and researchers, and on the regulatory side — FDA is an organization we partner with closely, so it's nice to have their perspective on this project as well.
The reason we've selected these specific partners is that, even though we're focused on the business aspects, which probably touch the sponsor organizations the most, since they're at the forefront of deploying digital endpoints in their trials, there are so many various stakeholders who are affected by the use of the digital endpoint. Whether it's the companies focused on developing the technologies, who need to know what's important for the sponsor organizations and how they're to be used in clinical trials, or so many other stakeholders, we really just wanted to have varied opinions at the table and to hear from all of them, to inform how we're thinking and ultimately what we'll be sharing with the broader community once we complete the project.

Yeah, I was very impressed with the list of partners you're working with. It's quite a diverse group, and I think that's something that's going to add so much value to the entire project — getting that diversity from large pharma to consulting companies to tech companies. So fantastic that you've picked such a diverse group. Victoria, maybe I should go back and cover some of the basics. I think a lot of our listeners know and are aware of digital endpoints, but could you give us a brief definition of what digital endpoints are and really what their significance is?

Yeah, and that was actually the very first place we started with this project. We wanted to define exactly what it is that we'd be focusing on. What's interesting is that I think everyone is quite familiar with what "endpoints" refers to and what that means in clinical research.

But the digital endpoint aspect is quite new to the field. So DiMe, which actually hosts a glossary on our website, has now incorporated a definition for digital endpoints as well, which we define as a precisely defined variable intended to reflect an outcome of interest that is, one, collected digitally with a sensor, and two, statistically analyzed to address a particular research question.
So this definition doesn't veer too much from the definition of a traditional endpoint, but it does incorporate that digital aspect. In layman's terms, it's an outcome of interest that's gathered via a sensor, and the sensors can be embedded into wearable technologies as well as applications on our cell phones. Ultimately, it's data that's gathered digitally. And why is this important? Because, as I'm sure we'll talk about a lot today, there are a lot of benefits to this kind of data. It's able to be gathered continuously, in real time, and it's gathered in the patient's natural environment, which provides unique benefits compared to seeing the patient in clinic or in person and gathering data that way. Because of that, the data tends to be richer — there's a lot more data to work with, and a lot of times it's more sensitive than what's perceived as the traditional way of gathering data. So that's where I think a lot of the benefits of digital health technologies and digital endpoints specifically come in. I'm sure we'll talk more about how these benefits translate, but just to give some context.

Yeah, definitely. Great, thank you very much for that really great overview. And Lauren, we love our clinical space, don't we? I know how passionate you are about this topic as well. How do you see digital endpoints changing the landscape of the clinical trials we're working in, if you look to traditional methods?

Yeah, of course. So Victoria mentioned some amazing benefits, which is of course the richness of the data, and how that really translates clinically is this opportunity to increase the frequency and volume of data being captured — talking to those unique data points Victoria mentioned as well. What this opens up the possibility for in clinical research is capturing continuous and passive data, which gives a lot more colour to the actual experience the participant in the trial is going through, because it's also capturing what happens in their home, not just at the more sparse site visits. And, as Victoria also mentioned, it's around that more natural setting, so we're capturing something that's a lot more realistic. To give an example of what that really translates to, it's things like comparing it to a six-minute walk test, which is done, of course, on a treadmill. That's quite different to how a participant would usually walk generally in their own home. Whereas if we're using a wearable and capturing that home data, we're actually capturing them popping to the kitchen to make themselves a cup of tea, which is a lot more natural than what they'd otherwise be doing on a treadmill.
What this offers clinical trials and sponsors is the ability to improve participant safety, as well as improving the amount of data we're capturing on efficacy, which directly translates to improving our likelihood of showing the possible impact that treatment option is having on the participant.

Fantastic, very interesting. We work a lot with biotechs, and I think biotechs are definitely organizations it's very interesting to pull into this research. How do you see them actually impacting the use of digital endpoints?

Yeah, I think this is a really critical point, and it's one of the reasons we're actually working with the Digital Medicine Society and have actively agreed to participate in this project, which I think is going to be incredibly exciting and impactful for our industry. The reason being that biotechs are primary champions for innovation, and more often than not it's actually becoming an expectation of them from potential partners and investors that they look for these innovations — so much so that it's largely becoming a requirement in order to survive as a business. So they have to constantly innovate to increase their likelihood of achieving financial funding to continue their work.

We also see that they're taking on these opportunities with vigor, but they also don't necessarily have the resources to really understand what other organizations are doing, what digital endpoints are being used. And as an industry, we're not very good at sharing what lessons can be learned. So we also see that being an innovator is actually really hard, and that more support is needed for them, because quite often they're the ones who bear the brunt of the lessons being learnt and getting their fingers burnt. So there's a lot more support that we need to do, and that's certainly our role in the project — to ensure that we keep that good link in with biotechs.

Do you see this as one of the hurdles, and could this be a call to action potentially as well — for both of you to call out to biotechs who are interested in participating and sharing their stories and experiences?

Yeah, I think what we're focused on in this part of the project is hearing exactly from these types of organizations, whether it's the large pharmaceutical companies or the biotechs focused on executing clinical trials. So absolutely, if there are opportunities to hear from them, we'd love that and be open to it, to help really inform how we're thinking about the deployment of digital endpoints and what their value is, from the large pharma companies to the smaller companies. We ultimately want to help the industry as a whole, and this is where I think biotechs, as well as any other company focused on producing clinical trials, have a really important say in how their work is affected by digital endpoints.

Absolutely. Their challenges are different to Big Pharma, which is why I think it's so important that we keep that good link in — they're the ones moving ahead and adopting these innovative digital endpoints, but they don't necessarily have the resources to support them. One of the main hurdles we see, because we work with a lot of biotechs who utilize these digital endpoints — which is really exciting and great to see, that they're at the cutting edge of innovation — is around validation. In the adoption of digital endpoints, it's fantastic that they're exploring that, but then having their fingers burnt because of a lack of validation means that, without the significant and required validation for the population group they're actually using the digital endpoint in, we can't necessarily use the data, which is critical for them and the success of the clinical trial.

Yeah, that's such a good point, Lauren. We always try to round up with some tips and tricks, and I think that's an important one for any sponsor — to really ensure their vendors and providers who are supplying these digital endpoints are validated, and that processes are in place for that. Do you think that intimidates organizations? Have either of you experienced that, to the point of not wanting to work with digital endpoints?

I'd say absolutely, because particularly if biotechs have had their fingers burnt in the past, they're less likely to do it again, which is not where we want to be — we want to be pushing innovation, adopting more digital endpoints. That's why it's really important that we're increasing the amount of support available for when they're actually considering these digital endpoints. It is a big ask — some of the validation work we've looked at in the past, to help sponsors who are mid-study with a digital endpoint they've then realized isn't validated for their study population, depending on the level they've already achieved toward validation, could take up to a year and cost over €100,000. So it's not insignificant, and it's not a cost that's expected, because it's a mid-study realization that suddenly has a big impact on your timelines and budget. That can be extremely off-putting for biotechs. But certainly that's why the selection of digital endpoints and vendors upfront is so important, and actually doing the qualification of certain vendors is so important.

And I think that's such a great point, Lauren, about validation — that certainly is a huge hurdle, especially given how relatively new a lot of these technologies are, and we're just needing more evidence around their validation. Another hurdle we keep hearing about, from talking to more organizations as part of this project and hearing from clinical teams, especially within sponsor organizations, is some of the operational complexities involved in deploying digital endpoints and digital health technologies. As these technologies are still relatively new, there are potentially additional trainings involved, additional support needed for using DHTs in clinical trials, and with that comes additional costs. As a field, we haven't yet developed a very strong muscle around deploying digital endpoints seamlessly, so I think with time, some of these operational challenges will become easier and probably not as big a hurdle. But currently that's another hurdle we hear about quite frequently.

That's interesting. Do you see that actually impacting the decision not to use digital endpoints in certain trials?

At times, yes, it does tend to be a deciding factor, because people will ultimately want to lean on something they're familiar with, or that already has a pretty clear pathway in the clinical trial. So that tends to be another reason.

I think return on investment is always important for key decision makers, isn't it? There are a lot of aspects to look at. If they're making the decision to move forward and willing to look at the investment that's needed, what do you see as one of the biggest returns on investment? Obviously there are different trials, and it could be specific to certain therapeutic areas, but would you say there's a general return on investment in using digital endpoints?

Yes, there is. We've actually already seen some data reported on this from a few publications I want to reference here. One is the study done by a group led by Hiro Mori, largely referred to as Project Moneyball, and also DiMe's recent collaboration with the Tufts Center for the Study of Drug Development, which was accepted for publication as well, where we showed significant return on investment in phase two and phase three clinical trials. That return was largely attributed to shorter trial duration and lower recruitment costs, because of needing smaller sample sizes. In terms of specifically what we're seeing on that return on investment, a lot of it is related to recruitment, because digital endpoints tend to be more sensitive and provide richer data, as we've been talking about. It allows us to screen patients more effectively at the very start — we're able to get a much more specific patient population to include in a study, which reduces some of the costs associated with recruitment. Additionally, because you're getting a more specific patient population, you need fewer patients overall, so there are a lot of benefits to using digital endpoints at those early stages around recruitment — we're seeing that ROI directly.
And then the other aspect of ROI is really captured in terms of treatment effect. Because digital endpoints tend to be more sensitive and provide richer data, we're better able to determine treatment effect and safety of the therapeutic much earlier in the process, which typically informs earlier decisions about the therapeutic and allows us to understand overall treatment effect and safety much earlier on — which can help inform future decisions in clinical development and can certainly reduce additional costs down the line. So treatment effect is another important aspect here. And to that end, if we're able to detect the treatment effect earlier, that means we can end the trial

sooner. Yeah, that's so true. We see the numbers around every month — what an additional month on a trial costs. And it's interesting, because often we see trials extend through change orders because of patient recruitment issues, so this can actually have a very significant impact. It'd be interesting to see a cost comparison — going back to the validation costs we talked about earlier, how that nets out against the savings in the long run, and whether it's potentially even more significant than the validation costs at the beginning stages of the trial. Is there data around that we could also share at the end of the podcast, looking at decreasing the number of patients required for trials?

I'd definitely refer everyone to check out the publication that was just published, the collaboration with the Tufts Center for the Study of Drug Development — there's very compelling data there, and I'd honestly love to see more organizations reference that in their work. That would be my first go-to data for the value of digital endpoints.

Yeah, absolutely, we'll make sure we reference that — we'll add it to the notes from the podcast today. So thanks for that. We've been talking a lot about sponsors, but vendors are also impacted, right? CROs and other vendors as well. Looking into the future, Lauren, there are so many stakeholders — what would be your top two or three bits of advice for organizations looking to implement digital endpoints in their trials?

That's a great opportunity to speak about the future. My top two or three would be, firstly, to be inspired by the opportunities — either as a tech vendor, by the advancements in technology and what we can actually create, or as a sponsor, by the amazing digital innovations being utilised today to benefit clinical trials and ultimately patients. But also to have a robust selection process — or, if you're a tech vendor, a robust pipeline for your product — to really get to grips with what the study needs, what your clients need, and what the patient population needs, so you can be very clear on what it is you want to achieve, because it's very important that the data we're using for a clinical trial is required and has a purpose, not just because it's nice to have. So it's important to be very clear on the why. And once you've been inspired, done the research, and invested in and acquired the technology you need, really learn from the community — the lessons learned through engaging with organisations like the Digital Medicine Society and other experts — in order to get the support you need for your operations, because it is challenging and it is new. But the benefits certainly outline the reasons why it's so important to consider, if not agree, to use digital endpoints.

Thanks for that, Lauren, great tips. Victoria, we've talked about the clinical side, CROs, vendors, and sponsors — but what does the qualification of the first digital endpoint as part of the FDA's Medical Device Development Tools Program mean for the future of clinical research? Do you see any impact on the regulatory perspective globally?

Yeah, I think you're referring to FDA's approval of Apple's AFib History feature as a medical device development tool, right? That was a huge, and first, big step.

Yes.

And honestly, I think we were all very encouraged in the field. I think it truly paves the way for future digital health technologies to gain approval as well. The regulatory aspect is crucial here — it guides a lot of the clinical research decisions being made, and we've talked a lot about validation, so anytime there's that kind of approval from a regulatory body, it certainly increases confidence and that kind of validation of a digital health technology. So my hope is that it only continues to increase our confidence in DHTs more broadly, and openness to actually using them in clinical trials. So again, such an encouraging development in the field, and I hope to see more of that.

Yep, very good — those are exactly the steps we need to take, aren't they, in order to move this forward. And going back to encouraging sponsors to take steps, because if they don't, who's going to do this, especially to share the information — just another big call to action. Any organizations interested in having a discussion, Victoria and Lauren will be very happy to talk with you, so let's plug that again. It's also interesting — we talk a lot with VCs as well, Lauren, we work a lot in that space. What do you think — should VCs also have their eyes open, looking at what their portfolio companies are doing in this space with digital endpoints?

So this is a really good one, because we've recently had a good number of incredible dialogues with VCs around the use of digital endpoints and their viewpoint on it. What we're seeing is that it's hugely attractive for them if biotechs are utilizing digital endpoints, for some of the reasons we mentioned earlier — the benefit of potentially reducing the timeline of the clinical trial by increasing the richness of the data, and therefore being able to better demonstrate treatment effect. That's becoming a lot more well known and understood, and it's certainly an attractive point for VCs when they're looking at where to invest next — it really should help the biotech or pharma company stand out, or at least be neutral, if it's a digital endpoint that's being more broadly used. I think the challenge becomes the fear of being left behind, so it's very important to be aware of what digital endpoints are being used within your specific therapeutic area, and to consider that impact — we generally move quite slowly as an industry, but we are certainly moving.

Yeah, definitely. And ultimately, we all know why we're in this business — it's for patients, and I think that's such an important part of this initiative, because ultimately we're looking at ways to improve how patients engage, and the ease with which they engage, in clinical trials. I'd really like to pull it back to that, because that's what the output is — obviously we're talking about digital endpoints, but ultimately it does get back to the patient. Have either of you had any feedback along those lines, from patients in trials, or around ease of use?

Yeah, absolutely — you're right, Sabine, it all does come down to the patients, and we certainly need to be thinking about them in everything we do related to clinical research and this work of trying to adopt DHTs more into clinical trials. A lot of the business benefits we've been talking about actually relate to the patients as well. Let's talk about safety for a minute — there are business benefits there, but there are enormous benefits for patients too. If a digital endpoint is able to identify adverse events earlier, or identify any changes in health status earlier, that can lead to better clinical outcomes, which directly impacts patients. And you mentioned engagement — what we know is that patients who are monitored with digital devices often report being more engaged in their healthcare, because they receive immediate feedback and insight into their health conditions. So there tends to be overall enhanced patient engagement, and that feeds back into clinical trials, because we know that when patients are more engaged, they tend to adhere better to protocol and treatment guidelines, which results in higher-quality data and more reliable trial outcomes. So this all loops back to the effectiveness of the trial as well — the benefits of DHTs for patients have also been largely looked at, studied, and are certainly important.

Yeah, absolutely. Thank you so much. I think there are so many more topics, and I know I still have a long list of questions, but I don't think we're going to be able to cover it all today. It could be interesting, as you move further into the project, to do a kind of midterm catch-up and see how things are moving along, so we'll definitely share the progress — everyone should have a look at the website. What DiMe is doing is amazing work, and we're thrilled to be a part of it and happy to be working with you and the team, Victoria. So thanks so much, Lauren, thanks for being on the podcast today as well — it was a pleasure. Let's watch this space, we may all be together again sometime after we start to get some initial data in. So thank you so much.

Thank you both.

Yeah, thank you. It's been such a pleasure — you've had such amazing speakers, so it's great to be invited on Cut the Chat. Thanks for the invite, it's a real honour.

Yeah, same here. Thank you, Sabine.

All right, out.