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James Riddle and Luke Gelinas Explore Digital Health and Regulation

March 22, 2021

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About the Advarra In Conversations With…

The future of healthcare innovation hinges on research and clinical trials. Advarra sits down with leading experts to dig into pressing issues and explore cornerstone solutions. Join us as we discuss topics and trends impacting the healthcare of tomorrow and advancing clinical research to be safer, smarter, faster.

About this Episode:

In this episode, Advarra’s Vice President of Research Services & Strategic Consulting, James Riddle, is joined by Advarra IRB Chair, Luke Gelinas, in an enriching discussion on digital health and regulation in clinical trials. Riddle and Gelinas cover an array of topics as they explore how COVID has been a catalyst for change, what digital health means for running clinical trials, and how sponsors, CROs, sites, and IRBs can consider when reviewing new digital technologies as a result of COVID. 

Discussions with:

James Riddle
MCSE, CIP, CPIA, CRQM
VP of Research Services & Strategic Consulting
Advarra

 

Luke Gelinas
PhD
IRB Chair
Advarra

Episode Transcript:

James Riddle (00:05:00): Hello this is James Riddle. I’m the Vice President of Research Services and Strategic Consulting at Advarra and my colleague, Luke.

Luke Gelinas (00:16:03): Hi! I’m Luke Gelinas, I’m an IRB chair here at Advarra as well.

James Riddle (00:16:03): Welcome everybody to Advarra’s inaugural podcast. This is our first series in the podcast of Advarra in Conversations With.

We’re going to have a conversation today about digital health regulation, talking about why clinical trials have been challenged during COVID. And also about how COVID has been a catalyst for change and what digital health means for running clinical trials. Also, most importantly, how sponsors, CROs, sites, and IRBs can think about how does an IRB goes about reviewing some of these new digital technologies and digital health that are coming in, as a result of COVID?

Luke and I are going to have fun with this conversation today; it’s a topic we’re very passionate about, so hopefully, Luke what do you think? Should we get going?

Luke Gelinas (01:04:25): Yeah, I’m ready, I’m excited. I think there’s a lot here for us to get into so let’s get on into it.

James Riddle (01:10:06): All right, very good so the first question to tackle here is

in the lead up to COVID, it’s been a lot of challenges in clinical trials with enrollment, with people having access to clinical trials, being able to get to the clinic and I think we’ve had a number of conversations about this, but just thinking about how did COVID really shine a light on these on these challenges?

Luke Gelinas (01:40:13): Yeah and I think even before we get to that, I can remember you know first getting into the clinical research space and thinking about, sort of, what are some of the main challenges here. And it’s always striking to me to realize the very low participation rate and basically the very low level of even awareness amongst the public when it comes to clinical research participation.

And I think, really, if you talk to researchers, if you talk to people who conduct research, one of the things they’ll consistently tell you is that they have a really hard time finding enough people to get in their studies and stay in their studies, and I think this is a giant problem. Not only in the sense that, sponsors it slows down drug and product development, but also from an IRB perspective in the sense that, many studies get up and running and they don’t actually finish, right? And when the IRB thinks about these studies and whether to approve them, we typically assume that they are going to complete and kind of meet their endpoints and produce valuable knowledge. And that’s part of what sort of justifies participants undertaking the burdens and risks of research. And so, when studies don’t find enough people, and they end up underpowered and they don’t answer their questions, it looks like subjects are sort of participating in this research in vain, and I think that’s a real concern and a real problem.

James Riddle (02:59:00): Yeah, I would completely agree. I have been concerned for many years that we have more trials than we have participants to go in them, sometimes. And so you have to wonder, from an IRB review perspective, if you’re not going to be able to attract enough people to be in the trial, does it really have appropriate risk-benefit ratio to enroll the first few knowing that you’re probably not going to be able to hit the enrollment target? And, to the point of people being aware of clinical trials, I would say I’ve had more conversations with family members and friends about participating in research in the last year than, maybe, in the last 20 years.

It used to be this little, you go to an after dinner party or whatever, and people would ask you like, what do you do? And you try to explain to them about clinical research and how ethics committees have oversight, and IRBs have oversight of the clinical research, and after you get to a like about the first five or six sentences of that, people would start to tune out a little bit, but now folks are really engaged, right? I mean they’re like, “How do I participate in these COVID trials?” and, “How do I get involved in research?” And the idea that research is hip and cool again.

Luke Gelinas (04:09:16): Totally I couldn’t agree more, and I think COVID has presented this sort of awesome opportunity for sort of raising public awareness around clinical research. I completely agree with you. Before COVID, when I would tell people that I was in clinical research, worked in an IRB, they had sort of no idea and weren’t at all interested to learn, frankly. But now it’s like, they know that people are asking me, “Well, what about the COVID vaccine trials, how are those going? Are they including pregnant women?”

I think the level of awareness and education amongst the public has soared, and that presents a real opportunity now to make inroads in terms of increasing those recruitment and retention rates.

We talked about the low participation rates. When you ask them, “why don’t you participate in research more?” it’s usually pretty mundane things like, I have to go to the site, and I just don’t have time to do that because I work and I have kids, or I don’t want to bother with parking.

So, I think that some of the changes we’re starting to see may help alleviate some of those obstacles, maybe we could shift to those.

James Riddle (05:09:07): Yeah, and some of the technologies that were available before COVID are now what I would consider being more commonplace, and I suspect that they will probably be around to stay.

The idea that a participant in a clinical trial has to go to a physical site to get their blood pressure monitored, and to have their physical exam, or their five minute walk test, or whatever it is that the protocol calls for. The idea that you have to go to a clinical research site between the hours of 8 and 5 Monday through Thursday… that excluded a lot of folks. It really excluded a lot of folks who might be in more rural areas of the country, who might not be close to a large population center with research sites. But now, there are technologies coming onto the marketplace that really help and support mobile visits.

Luke Gelinas (06:05:01): I feel like we had been hearing for years about kind of the coming decentralization of trials and how mobile health technologies we’re going to remove the need for in person visits.

I think COVID has really accelerated those trends and brought them home and I’m not sure we’re going back, and I think you know, maybe we could talk a little bit about whether, what sort of benefits, and maybe some of the risks and challenges are for that.

I think we’ve already touched on some of the benefits of when you have these technologies, mobile health technologies, that are capable of collecting data at home, telehealth that permits visits via remote modalities and Zoom and the like. You have home healthcare workers who are increasing increasingly being leveraged to come into the home and to administer research procedures.

That really sort of democratizes research, right? And it improves access for people, it allows, as you referred, as you sort of alluded to earlier James, lost populations that may not have been able, previously to participate to now have the ability to do it because they don’t have to leave the home, they don’t have to find childcare. So I think from sort of a patient-centric perspective, this has the ability to be a real game changer. But I wonder, too, if there’s also some potential concerns and challenges, and I’d love to hear, kind of, your thoughts about what you see as the challenges of that.

James Riddle (07:20:10): Yeah I think from my perspective, what I hear your talking with colleagues and talking with sites and sponsors, there is a general concern that moving to more remote, decentralized trials with different technologies for virtual visits, virtual trial technologies, whatever language you put in there, that it is different to have a remote monitoring device measuring somebody’s blood pressure or somebody’s health, versus seeing them in person.

The doctor-patient or investigator-participant relationship, has been an in-person kind of affair for however long we’ve had these things going on, and to go to a more virtual environment, maybe not completely virtual, but where you’re integrating virtual trial technologies into the clinical protocol, there is an element of having to wonder, am I getting as good of data?

One of the examples, I was having a conversation with a friend of mine at a site, and they were concerned, because traditionally, a participant would come to the site, they would get their blood pressure monitored by a technician on a calibrated device that was known and monitored and maintained. And this first person was pretty concerned that a clinical sponsor had allowed for the idea that they could get blood pressure information from a remote device. So basically, their concern was, “Gosh, when I’m doing it myself, I know I put the blood pressure cuff on correctly, right? I know that my equipment is calibrated correctly. And now I’m going to rely on a participant who’s not trained, using their smartphone, or smartwatch, or whatever, to get an accurate reading.”

Ultimately, the data that goes into these clinical trials, is going to end up being part of a regulatory submission to a regulatory agency, whether it’s US FDA, EMA, somewhere. And the regulatory bodies are going to make decisions about whether it’s safe and effective, these new compounds, based on data that was collected at the clinical research sites.

We have to be able to trust that data. I think a lot of the resistance in the past to using these more remote virtual trial technologies really did boil down to: Can we trust the data that’s being generated?

So from an IRB perspective, when these virtual trial technologies show up in a clinical protocol, how does the IRB you know evaluate how the risk-benefit ratio of the research is adjusted based on these virtual trial technologies?

Luke Gelinas (10:07:17): Yeah, I mean I think there’s a few things to cover there. I wanted to just comment on the data integrity point first, because I think it’s a good one.

Can we find ways to, sort of, confirm that this data collected out there in the real world is good? I think there’s kind of another side to this, so there are challenges. But you know, we’ve also been hearing about kind of the value of real-world evidence for a long time now, and so there might be an upside as well, although I think there are challenges and sort of opportunity. The opportunity might be that some of these remote modalities have the ability to sort of pick up on data points that would otherwise be missed in an in-person visit, right?

People who are suffering from certain conditions might have symptoms that don’t show themselves when they go to the doctor’s office. It’s like when you have a noise in your car and as soon as you take it to the mechanic your car will always stop making that noise, right?

James Riddle (10:57:05): I know that, I know that happens to me!

Luke Gelinas (10:59:24): It stops! And I think it’s the same, some people have that experience with their medical conditions, right?

So these devices have the ability to kind of track and monitor people, and in real-time, and their real lives, and pick up on things that might otherwise be missed and that could be a beneficial thing. I don’t think it removes this challenge of how do we confirm kind of the central liability of the data, but it’s sort of an interesting opportunity and potential benefit that will be really interesting to see how that sort of plays out and how the regulator’s kind of parse the data and what their standards are when it comes to sort of assessing remote data on this.

But to your point, one of the big things on the IRB we worry about when we see these protocols are sort of privacy and confidentiality concerns that stem from use of these remote technologies. I mean, some of them, and I’m thinking of here like wearables, smart devices, that are usually configured through apps on your phone, collect incredible amount of data, and some of it is quite fine-grained. We have, you know, sometimes tracking apps collecting location data, they collect everything from your sleep patterns, to your movement patterns, to your heart rate and blood pressure, and so on. That’s just a tremendous amount of data to be collecting about people that have privacy implications. Some of it is inherently identifiable, some of its not. I think we do spend a lot of time wondering about, you know, are people sort of adequately informed of the privacy implications and are we worried at all about confidentiality breaches? And how do we protect against them, and protect people’s data?

James Riddle (12:32:26): That’s definitely important concerns and I think that just in reviewing protocols that have these virtual trial technologies embedded in them.

Just within the last 5, 6, 7 months, I think sponsors and CROs have gotten a lot better about describing how these virtual trial technologies are embedded with inside their protocols, the options that are available.

And I think some of the vendors too, have gotten a lot better about describing how their devices work, providing that information to the IRB. So that has been super helpful, and I really do hope that that trend continues. That really helps the IRBs, whether it’s us or some other IRB, or research ethics committees around the world, we all have sort of the same kinds of questions.

And so, to the extent that the sponsors and CROs can put that information into the protocol for us, it makes the review process just that much easier, I would imagine.

Luke Gelinas (13:29:26): I completely agree the more information you have about these devices, the easier the review is.

We’ve kind of been dancing around this question of access, which I think ties to notions of justice and fairness and enabling research participation. When we review these protocols, people who are economically vulnerable, who may not either have access to these technologies, or who may not have the savvy to use them correctly, which ties into these other points about data and so on. For studies that use these technologies, should sponsors, as a matter of course provide, let’s say, a smartwatch or a phone to someone for the duration of the study, or is it a reasonable expectation to limit enrollment to only people who have these certain devices? Is that compatible with considerations of fairness and justice?

James Riddle (14:15:15): Yeah, and Luke, that’s a really good question, because if you’re thinking about integrating a virtual trial app, so some kind of like eDiary or any kind of remote monitoring, or some something along those lines, sometimes those applications, if you don’t have your own smartphone, you can’t participate, right? Or you don’t have Internet access.

I think, best practice, just to address your question, best practice still feels like you would take a hybrid approach that, particularly for clinical research trials, that might have some potential for therapeutic benefit. So, think Phase 3.

To have the option if people don’t want to use the technologies, to go to the clinic in a more traditional sense, and so what I’ve been seeing in a number of protocols, and in vendors that provide these virtual trial technologies, is that they’re working in an optional environment.

I actually think that the utilization of these virtual trial technologies is improving the justice issue and access to clinical trials in a way that we weren’t able to before. If you think about who in this country has ready access to clinical research it’s generally people who live in fairly large population centers, who can have the economic means to be able to volunteer to be in a clinical protocol, and sacrifice and volunteer their time to go. Well, that excludes a lot of people. But if you can have home visits, remote monitoring, you can provide people with more flexible options. Personally, I think that actually increases the reduces justice issue, but it increases access to clinical protocols that, to people who maybe wouldn’t have been able to participate in the past.

Luke Gelinas (16:08:19): Although, I also agree with you that overall it is helping access, so where do you think we’re going with all this?

James Riddle (16:18): It’s a really good question. So, first of all, I think virtual trial technologies are here to stay. I think that COVID, as a population, we have adopted the idea of Telehealth.

I don’t think we’re going to get rid of, or eliminate the principal investigator at a clinical research site interacting with the participant, in some manner. In the idea that you would be able to do a clinical trial completely virtual without any kind of physical interaction works for some trials, maybe Phase 4 post-marketing maybe some late Phase 3, where the compound is in a stable form that can be shipped through the mail.

But if you’re talking about Phase 1, Phase 2, any kind of research that involves visit to a clinic to get an MRI, or scan or something that can’t be done in the home, you’re always going to have that participant-Principal Investigator relationship. So I think what we’ll continue to see is more flexibility on doing telehealth for visits.

Luke Gelinas (17:23:26): I fully agree and I was really struck relatively early on in the COVID pandemic with FDA who basically issued guidance more or less promoting the use of these remote modalities for data collection during COVID. So I think the fact that the regulators seem to be encouraging of this – not  just the way I read FDAs guidance on this, is that they’re not only sort of permissive of it, they’re almost recommending it, at least during COVID-19.

That to me, suggests that we’re probably not going back. As long as, I think it makes sense from an economics perspective for sponsors, and I think that ties back into the earlier point: If these trials really can increase recruitment and participation rates, then that is going to make sense for sponsors. When you have to shut down and study early because of lack of recruitment and accrual, that’s just the killer. You’re wasting all those resources of conceptualizing the study, getting it up and running, and now you’re getting nothing from it. If you can actually improve participation rates, to the point where you know you’re minimizing the number of studies that have to shut early, you’re getting more studies done more quickly. And, as a result of these decentralized modalities, then I think sponsors are going to love that, and there’s no going back.

James Riddle (18:47:14): And I think we get a little bit of a clue in the FDA guidance on how to conduct clinical trials during COVID, a few of the more recently added frequently asked questions in that guidance, have said things like:

Yes, you can do really cool e-consent, remote consenting, kind-of-activities, but you still need –this is the James Riddle paraphrase version – to make sure that those electronic consenting tools that you’re using are validated for Part 11 compliance, right? And that kind of language really leads me to believe that FDA is probably going to draw back a little bit when the pandemic ends, because, and you know it really does boil down to: How does FDA know that they can trust the data that’s being collected by these software programs? And the way that they know is they make the software vendors follow the guidance on computer software validation. Which, for those familiar with that, it’s FDA is testing methodology. It’s what you have to do to prove to the FDA that your software works the way it’s supposed to and generates the data that’s supposed to.

Luke Gelinas (19:56:02): Yeah, I mean that drawing back seems totally reasonable. I mean, we can get all excited about it at the IRB and research site level, but I think it does, it is so important to keep in mind at the end of the day that we’re doing all this in order to produce data that can be, you know, assessed for liability and to essentially to try to figure out whether it’s investigational products warrant are safe and effective and warrant marketing, right? And so I’m kind of reassured, actually, now that I think about it, that the FDA probably wouldn’t rush into this maybe as quickly as some of the rest of us would.

James Riddle (20:33:10): I’ve been really encouraged with the level of flexibility from the agency. They were really out front with, look, we need to keep clinical research running, this is really important. And so FDA was really, in my opinion, out as a leader on this.

The independent IRBs, we were all very good about putting out fresh guidance and, as much as we possibly could, creating flexibilities for people to work with. And those flexibilities – we’re  going to have to solidify around some of them.

Luke Gelinas (21:04:24): Yeah, I just want to come back to the earlier point, which is that I think, again, COVID has raised the profile of clinical research, and I think we have a real opportunity, just as a community, to kind of make inroads with the public, gain public trust, you know, continue to be transparent, and the IRB is here to protect the rights and interest of the participants. But we’re also generally pro research, you know, we want to see therapeutics advance, we want to see new cures and treatments for patients, we want to facilitate research.

I think we have a real opportunity, given now due to COVID, to essentially, kind of, continue to educate the public and show them what we do and to, you know, increase public uptake and trust and research.

James Riddle (21:49:13): Alright well hey look it’s been a pleasure; I hope everybody has enjoyed our first episode of Advarra In Conversation With. If you liked this particular episode, make sure to follow us on LinkedIn. All of our most recent content always gets posted on LinkedIn: blogs, white papers, webinars, podcasts, etc. Or, you can visit our website at advarra.com, and we’ll look forward to talking to you again on the next podcast.

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