Navigating the Path to Approval for PDTs Using Decentralized Clinical Trials

Insights From DTx West 2023

Craig Gravina, chief technology officer, ObvioHealth, sheds some light on the current digital therapeutics landscape, including regulatory challenges, the prescription DTx model, and solutions to improve clinical trial research. 

Read full transcript:

Welcome back to Pop Health Perspectives, a conversation with the Population Health Learning Network, where we combine expert commentary and exclusive insight into key issues in population health management and more.

Today we’re joined by Craig Gravina to discuss digital therapeutics or DTx, including the prescription model and ways to improve clinical research.

Nice to meet you. I'm Craig Gravina and I'm the chief technology officer at ObvioHealth. ObvioHealth is a decentralized clinical trials (DCTs) provider and we offer both the platform and the technology to deliver decentralized trials, as well as the services related to protocol design, study design, data management, and all the operational aspects of running a trial. 

A bit about my background, I have primarily been a tech entrepreneur most of my life. Second half of that being in the health care space, and so have done quite a bit of interesting products and solutions within the provider market, the payer market, and the pharma market. I've kind of covered all the major Ps and I think it's a tremendously fun environment to work in.

Can you describe some of the main challenges emerging as digital therapeutics gain popularity?

What I believe any DTx provider is struggling with is the regulatory environment and how they navigate a DTx through the complexities and rigors of a traditional pharma-based trial, while still making sure that we're taking advantage of the ability to bring solutions to the market fast—like any app-based or tech-based provider would. I think the regulation is certainly challenging for DTx companies in general to just begin to get their arms around, but there are also more and more DTx companies taking a dual approach or maybe not even pursuing prescription because the device doesn't really necessitate a prescription, but clinical trials are still important to providing evidence of efficacy and so forth. So I think there is a challenge amongst many right around which of those paths to pursue or whether you pursue both in tandem.

Regardless, I think there are greater challenges around the way that evidence is collected, way that outcomes are measured, as well as the operational aspects of how you deliver a trial and then monitor safety and efficacy over time. That’s really the area where I think we have really focused our research and the clinical science around the measurement of evidence is in eliminating some of those challenges. What I mean by that is when you are working in a traditional pharmaceutical world, you remind somebody in the trial to take their medication. You are complimenting the medication adherence aspect of things. It's not introducing any noise into the data. When you're dealing with an app as the therapeutic itself, there's a certain amount of bias that you may be injecting into the utilization of the app.

Typically, a decentralized clinical trial will use an app—as ours does. That app usually is sending reminders to go fill out questionnaires or do activities, maybe schedule events. In the case of a DTx, that typical approach would be, hey, I'm reminding you to go use the DTx. The reality though is that many of these DTx, the actual therapeutic is the fact that someone is using the app on a regular basis because they enjoy using the app because it's providing them benefits. They may be monitoring their health and just by virtue of monitoring your health and caring for yourself more, that is the actual therapeutic. So you wind up in this conundrum of am I influencing and biasing people to use the therapeutic vs is my therapeutic and app compelling enough that someone is going to use it on a daily basis and then take advantage of the therapy?

So I think that's an kind-of-yet-undiscovered issue that is going to surface around the truly app-based therapeutics and one of the ways that we have solved that is by providing a conduit to capture the outcomes and the evidence directly from the therapeutic so that we minimize the amount of redundancy in initiating an action or the taking of the therapeutic. Thaat's one piece that I think is a challenge. 

The other challenge in the DTx world is a lot of the regimens that are provided are actually the same kinds of clinical scales and instruments you would need to measure the efficacy. So for example, a mental health DTx is typically going to administer the PHQ-9 and the GAD-7, CNS scales to determine various aspects of your mental health.

Those are also typically the scales you would use to measure the efficacy of the drug or the therapeutic. So you don't want to ask the participant in the trial to fill out both those forms. By being able to capture data directly from the use of the therapeutic, we can eliminate that redundancy and really treat the app or the DTx in itself as the primary interaction with the participant and the clinical trial app becomes a conduit for collecting outcomes as well as the complement to add additional evidence to the measurement of its efficacy. 

Those are some big challenges that I don't think have yet surfaced as widely as just the regulatory challenges, but one that I think is going to become pretty widespread and one that we've anticipated and created some unique methods of collecting data directly from the therapeutics.

What technological solutions are available to mitigate challenges in DTx trials?

The DCT technology—the decentralized clinical trials technology—is really well married to the whole DTX clinical trial approach. You are typically dealing with therapeutics in this space that are done from home. There really isn't a lot of requirement to visit a site. People are mobile. So having that same approach to the actual trial as is taking therapeutic, I think, lends itself well, not just to the methods of collecting data, but to the user experience in participation in the trial. 

I talked earlier about the technologies of eliminating bias and adherence and reducing the amount of redundancy in collecting outcomes from the participant, but another piece that is important and one that we are certainly creating solutions for is understanding the usage patterns and the behaviors of users when they're interacting with those DTx.

So, again, it may be that there is a specific regimen that you want to see in the app usage that may just be as simple as did you use the app—which would be the equivalent of, “Did I take the pill?” But the reality is that it's more complex than that. It might be, “Did I use the app and did I read the health management content that was provided to me in order to better care for my condition?” “Did I engage in the exercises that were required for me to do the therapy and did I do them for a long enough time?”

I think you have these DTX apps that are becoming more sophisticated and you have a scenario where there's the technology of DCTs is catching up to how to measure a DTx, and that combined with we're a mitigating bias and redundancy in the outcomes capture is really what the DTx APIs that we have developed on top of our DTx platform are really meant to address.

How does the trial process vary for prescription vs nonprescription digital therapeutics?

I mean, to some degree it's the same process and it carries along with that all the rigor of evidence and so forth. There have been some programs that the FDA has put forth to try to accelerate some of these DTxs. I think there is actually an advantage that's beginning to surface in the regulatory world to try to keep up with the pace of technology and afford paths to regulatory approval that take into account the speed at which a DTx might progress in its drug development process than a traditional pharma based therapeutic might. 

When you think about the differences between a prescription or nonprescription element is really about a trial—it probably really comes back to how do you accomplish the clinical oversight in a DTx trial with the rigor that you would in a traditional pharma-based trial.

In most cases, that participant's not coming into the site. So you need to have the various methods of capturing more clinically relevant data than just ePRO and questionnaires. It's typically going to be less obvious when a patient is experiencing an adverse event and you may not have only the ability to detect it, but also the ability to diagnose it as well. So I think that’s where you wind up with the challenges and I think there are benefits that you could take advantage of with a DTx that you probably couldn't necessarily do in the world of prescription- or pharma-based trials. Those are things that kind of counteract that same statement.

There are ways to monitor vital signs and a lot of these DTx may already be doing that. There is ways to facilitate communication and telehealth based assessments. 

So a lot of DCT providers will say, "Well, we are building an advantage because we're eliminating the site and we're eliminating the site visits and therefore you have less costs." I think that's the wrong way to consider it. 

It's really about how can you capture better evidence in the trial and how can you facilitate the kinds of activities that might happen at a site for the basis of better monitoring and oversight of the patient's progression. In an electronic world where we are able to capture the utilization of the DTx, the outcomes from the DTx, and be able to service that directly to the care coordinators and the clinicians that are monitoring the trial, you really wind up with a better conduit to the state of the patient.

Great, thank you. Our next question, what populations do you envision benefiting most from DTx?

Historically, diabetes has been one of the first avenues that people have entered into from a therapeutic area in DTx. A lot of times what I think it's an easy one to understand because people say DTx and they think just apps, but a lot of the DTx solutions in the diabetes space are using devices to measure glucose levels and other things. 

You really have to think about this as not just an app, but potentially an app in a companion device as well. We have done quite a bit of work in women's health, and when you are dealing with conditions that are addressing urinary incontinence and other women's health issues, there are typically that kind of companion app and the vice therapeutic that are treating the condition.

The ability to participate in the trials from a remote location in the privacy of somebody's own home are areas that really, we've seen a lot of traction in the DTx and the embracement of DCTs. The obvious one is within CNS, right? When you're dealing with cognitive issues or behavioral issues, there's a tremendous amount of ePRO instrumentation that interpret to a regimen of maintaining your health as well and self-monitoring a health. Also, the correlation between the actual delivery of the therapeutic and the measurement is extremely high. There's a lot of overlap. I think that's an area that's poised to have accelerated trials and so thus might be an area that really gains traction more so than just from the condition itself.

Beyond just looking at populations from a condition perspective, you obviously have other types of areas that are interesting to focus on in terms of location and being able to reach a remote patient pool. A lot of chronic disease sufferers are in these remote locations, so I think those are the chronic disease and health management and coupling that with a remote population is I think a very synergistic environment for the DTx. Then I think the other piece that the clinical trials environment has suffered from is the diversity in the populations that are participating in the trials. So again, I think with DTx, given that there is no reliance on location or proximity, you wind up with better ways to potentially recruit participants, there is also an opportunity to really expand equity and access to these kinds of DTx as well.

Is there anything I haven't asked you about or anything that you'd like to add?

I think in general this space is one that is going to continue to evolve at a very accelerated pace. Traction has already been accomplished. There have already been some predicate devices and pioneering companies that have launched product to market in both the nonprescription as well as prescription model. 

I think the area that it really needs to accelerate even more aggressively is that wider support across the clinical research environment and the companies that are delivering trials or providing the technology for trials or finding ways for sites to participate in these kinds of trials to accelerate the time to market for these therapeutics. The regulatory bodies like the FDA have put programs in place to accelerate it. I think now the challenge is for the clinical trial and clinical research ecosystem to try to provide ways to accelerate the driving product to market as well.

Thanks for tuning in to another episode of Pop Health Perspectives. For similar content or to join our mailing list, visit populationhealthnet.com.

This transcript has been edited for clarity.