The Latest on Digital Biomarkers, with Regeneron’s Rinol Alaj
Digital biomarkers offer industry a potential way of running trials faster, more effectively, and with greater patient centricity. Senior Director, Head, Digital Health Technologies, Rinol Alaj, MS, MPH, MBA, lends his expertise in digital biomarker development to outline how Regeneron approaches the space, the critical questions that need to be addressed, and keeping science at the center. Mr Alaj will be leading a panel discussion on the topic at DPHARM 2024.
You’re on a panel at DPHARM 2024 focused on advancing scalability and operationalizing digital endpoints in clinical trials. What can people expect from this discussion?
We’re looking at how we can run more effective, faster trials that are patient-centric. Digital biomarkers are a component of that. It is a relatively new field and area; some companies, including Regeneron, have been working in this space for a while, and others are more recently getting into the work.
We want to use the expertise from our panelists to share the journey, the challenges and lessons learned in developing and validating digital biomarkers, as well as executing them in clinical trials from an operational perspective.
We also hope to discuss how we incorporate digital biomarkers into program-level planning, versus viewing them as merely a technology that measures physiological functions. During the panel we will explore what that means and the benefits of starting with scientific questions at the program level.
Beyond the mechanics of operationalizing biomarkers, what else is important to include in this conversation?
The most important part of this work is collaboration. I hope to explore what opportunities there are for collaboration and ask the panelists how we can best work together, as an industry, to advance biomarker adoption.
We can’t do this in silo, and that’s one of the reasons why we host the annual Digital Biomarker Summit at Regeneron, which is an event that brings together different leaders from the industry, academia and research to create an environment that promotes collaboration.We compete on drugs, not digital biomarkers. Therefore, we need to promote working together in validating and developing digital biomarkers to advance this work.
"We may be intrigued by a technology and want to put it into a clinical trial, but if we’re not understanding the scientific rationale, it will fail."
How do you incorporate digital biomarkers into program-level decision-making?
At Regeneron, we always focus on the science and approach digital biomarkers in the same way we approach drug development. We may be intrigued by a technology and want to put it into a clinical trial, but if we’re not understanding the scientific rationale, it will fail.
We start at the program level in advance, even before getting into a Phase I study, looking at the disease in general, the area that we're studying and identifying the unmet need. We ask: What is the concept of interest that’s important for the patients? What are the opportunities for digital biomarkers to measure physiological changes that traditional endpoints or measures do not provide? How do we identify those early on and convert them into endpoints?
From there, we test those devices in the lab to make sure we can actually measure what we intend to, and then define the outcomes from there and what a meaningful change would be from the traditional method.
What needs to be included in success for digital biomarker development?
Success is measured in multiple ways.
One way for us is making sure we have the right teams, resources and experts involved and ensuring that we have the right processes in place to have the discussions early and identify what endpoints are needed. Developing digital biomarkers is complex and requires different functions and groups working together: digital biomarker engineers, clinicians, data scientists, clinical trial managers, operations, user experience, and more.
You need those different perspectives when, for example, discussing what benefits a digital biomarker can bring in better measuring functional decline, specifically in areas where we measure longitudinal decline due to disease progression, and where we can improve our signal-to-noise ratio for these functional design characteristics.
Another way we measure success is by how many publications we’re putting out per year, what impact we’re having on the industry, how we’re sharing the data, the number of endpoints used in primary versus secondary versus exploratory, and then how many studies are using digital biomarkers for internal decision-making.
"You need to be smart about what you’re investing your resources in, but it always comes back to the unmet need and the value you’re bringing."
How does a resource-constrained environment affect investing in digital biomarkers?
You need to be smart about what you’re investing your resources in, but it always comes back to the unmet need and the value you’re bringing.
You need to determine if it’s the right therapeutic area, the right biomarker, the right disease state, and where digital biomarkers can bring true value. There are areas where digital biomarkers are not as potentially beneficial, but there are a lot of areas, particularly where we see functional decline, where digital biomarkers can bring a lot of value.
The right digital biomarker can lower variability, increase effect size, and potentially lower the sample size required. It might be an investment upfront, but if it shortens trials in the long-term, then we’re able to potentially deliver therapeutics to patients faster. That’s the goal.
How is Regeneron working to validate biomarkers more efficiently and effectively?
The fact that we’ve established the ability to run these validations faster is a big win for us. We have established a Digital Biomarker Lab at Regeneron, which is a specialized facility that has reference methods and specialized equipment for verification. That allows us to conduct design simulation and test these wearable devices from both a verification and validation perspective, before we put them into a trial.
We can validate these biomarkers much more quickly than if we had to outsource them to a third-party device vendor, which could take a year or longer. We’ve done this work to have the capability and capacity to validate biomarkers quickly, work with vendors once we select the technology, be able to measure against reference methods, and ensure that the tools measure what they need to in controlled settings and with the introduction of confounders.
"There are a lot of areas, particularly where we see functional decline, where digital biomarkers can bring a lot of value."
What are the most critical questions of digital biomarker development that need to be accounted for?
First, what is the scientific need, and is there the ability for a device to measure what it needs to?
Second, is it usable, from both the site and patient perspectives? We have a User Experience Research team at Regeneron, where we test how a device fits within the patient lifestyle; we also have our Digital Biomarker Lab. On top of that, we conduct different types of usability testing and user experience research testing, where we gather direct feedback from patients on their experience with the devices that we plan to integrate into the study.
Third is the operations aspect. How can we scale it at large within a clinical trial?
Looking to the future, what are the hurdles you’re facing in your work?
One challenge is picking where to focus. How can we focus our resources in the right area, unmet need, or outcome? There is not much literature available, so it can be difficult to make the right decision or move in the right direction.
And then there is the complexity of data in large-volume data sets. How do you make sure you’re analyzing and processing the data to make the right decision?
Another reality is that a lot of the vendors in the space are newer. As we scale into larger, global clinical trials, we need to make sure that these vendors can send devices to all these different countries, especially when they require different regulatory approvals.
There is also the regulatory aspect. What are the needs? There is guidance published by the U.S. Food and Drug Administration (FDA) on digital health technologies, but it’s still a relatively new space.
The last challenge is having the right training and resources for our internal staff to be able to support the volume of work we have.
All in all, digital biomarkers are a promising field and just one of the many ways in which we are looking to innovate and modernize clinical trials.
