Decentralized Clinical Trials and Regulatory Changes

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About This Episode

DCTs are more than just technology! In this episode, we discuss the evolution of decentralized trial modalities, tailoring clinical trials for the participant population, and possible solutions to regulatory challenges.

Chapter 1: Defining Decentralized Clinical Trials

00;00;03;26 –> 00;00;23;02

Hi, everyone. Welcome back to the Advarra in Conversations With… podcast. I’m Julie Ozier, the Senior Vice President for IRB Review at Advarra, and I’m thrilled to explore decentralized clinical trials or DCTs, as you may hear them today, with the Chief Scientific Officer at Medable Pamela Tenaerts.

00;00;23;02 –> 00;00;55;01

Thanks, Julie. I’m excited to be here today, like you, said I’m the Chief Science Officer at Medable, and as such we really try to understand evidence or create evidence, best practice and important policy with the work that we do here, and obviously decentralized clinical trials and the regulatory changes that they sort of lift the landscape that’s changing around this are sort of top of mind for me, and always excited and interested to talk about how those are shaping the present and future of clinical trials which we all hope are going to be better than the ones we’ve had in the past.

00;00;55;01 –> 00;01;20;04

Absolutely well look great. Let’s just jump right on in. As you said, I think you’re right. It’s becoming a little more commonplace for folks to use DCTs, and there comes a lot of benefits with that. But then also a lot of challenges, and I thought maybe we could sort of explore some of those benefits and challenges and think of different ways of doing research within a decentralized model.

00;01;20;04 –> 00;01;55;23

Great. And I think maybe what where we could start is with the definition, because it’s one of the centralized trials are one of those terms that people have different visions of when they heard here the term, so the one that maybe we could start with is the latest one that was described in the FDA Omnibus Reform Act. The FDORA Act that was just signed in December. They describe it. It’s an American legislation, so obviously it’s American but I think it describes it pretty nicely that a decentralized trials, a clinical study in which some or all of the study related activities occur at a location separate from the investigator’s locations.

00;01;55;23 –> 00;02;58;00

So, it means that there’s different DCT configurations, such eConsent the use of clinical outcome assessment captured on your phone or web. So eConsent, and other things, and that these elements should be fit for purpose and based on the study populations, the condition under study and the phase of the development and the goal going back to what we hope these the technology or digitizing clinical trials will enable is that we can improve participants access and experience while maintaining their safety. We also hope to improve the site experience and then also maintain an improved data quality and increased study performance. And what I mean by that is sort of due to things better operationally in a clinical trial, which means, maybe ending faster, finding, you know, enrolling faster, improving a diversity, a lot of talk about that trials need to represent the diversity of the people living with the condition. So maybe technology can be used for that as well. And then also, eventually we hope that it will reduce cost.

00;02;58;00 –> 00;03;40;13

So with that, I think I mentioned some of the benefits. Some of the other things that that may happen unintentionally is that with digitization, we may be excluding a group of people that don’t have access to technology like other people have. And there’s a really interesting article that was in The Atlantic in the last fall that talked about the pandemic legacy, and there they said that technological solutions tend to rise in the pandemic pent houses whereas the inequity seep into its cracks. So it’s kind of this idea that technology is not evenly spread across a society, basically and how we can use technology to overcome that.

Chapter 2: Representation in Decentralized Clinical Trials

00;03;40;13 –> 00;04;32;18

I love how that you mentioned, and that the also the definition mentioned that it’s more than just technology. It reminds me of the study where they were testing blood pressure in African American men and their awareness of it, and they took the study to barbershops. So they took the study where the participants were, and it was just a lot easier to be able to recruit when you’re in the area that they frequent. And so it’s not all technology like you said, but absolutely it is. Technology is one very, very big piece of it. And I like how you mentioned the digital divide. That is so. True. You know the elderly or the people that don’t have Wi-fi signals readily available or don’t know how to use an app on a phone. You know you have to be able to include those participants as well.

00;04;32;18 –> 00;05;31;14

Totally agree. And I think I mean we’ve all heard the statistic that 70% of people in the US live more than 2 hours away from a research site. So just right there, logistically, it’s probably hard for people to get to a research site. So how can we get closer to them? You mentioned the barber shops as one option, I mean the other option is using home health nurses, having people come into their houses or maybe get closer into their communities in in places like retail pharmacies or grocery stores, and sort of incorporating all those things like really go to where the people are, so that they can participate. That also means, by the way, that we need to think about potentially the research site as a as a different site than what it’s traditionally been. And maybe it’s more of your local physician and your local hospital systems that can participate in research. And as you mentioned, all of that is likely enabled by technology. But we need to think of all those things.

00;05;31;14 –> 00;06;01;21

Absolutely, you know, and it and it in thinking about this and searching for what participants might actually want, it seems that with some diseases and maybe some studies. There is a little bit of face to face that they would want as opposed to being all remote or all tele health. So I think a hybrid approach is really interesting, and might even be better to offer participants sort of their choice of how to do it.

00;06;01;21 –> 00;06;21;01

Exactly. And I think when I think of DCTs I’m probably pretty much in the middle with a hybrid approach. I don’t often think of it as completely decentralized, and we just need to make sure that we give people options because the participant population is also not monolithic.

00;06;21;01 –> 00;07;12;06

So while in, I think, 2016 or 17, which is now a little dated that maybe the numbers are slightly different. But when I was at Clinical Trials Transformation Initiative (CTTI) we asked people if they wanted to participate in what we then call the mobile clinical trial, a trial that allow technology to, you know, to run the trial. And in that survey we found that about 70% of people said they would prefer it, but that then also means 30% of people did not, and it may just be situational. There may be days that if I’ve been on the phone all day long for work, maybe I want to go outside and go see. Go to the research site to just do something different, and maybe some days I don’t so. It’s giving that optionality. I think what it’ll be important. And just to remember that different disease different conditions may have people more likely to choose one over another, but that doesn’t mean all of them want that or this other thing either.

00;07;12;06 –> 00;07;26;27

Absolutely. It is so interesting, though I read a statistic the other day that said that during the pandemic that 98% of patients were happy with telehealth visits as opposed to coming in. So that’s really interesting. That’s a lot.

00;07;26;27 –> 00;08;20;10

That is a lot. And maybe during the pandemic that was driven by whatever the circumstances were back then. But maybe now some people actually might want to come in. So I think it’s important to know that what we thought had to happen, which was a participant needed to come into the specialized research site. That probably wasn’t exactly true, because we now learned that people actually don’t mind doing things off their phone or using telehealth. But what it also doesn’t mean is that they exclusively only want to do those things ,right. I was at a site for 12 years, and we had a group of people come in. They became friends. They had to sit there for a long time doing pulmonary function tests and sort of over time. They like coming in. They became a group of friends that were playing cards while they were waiting on their next assessment. 30 min, an hour. And so you know. Some of those considerations also need to be taken into account.

00;08;20;10–> 00;09;12;09

Absolutely. And I wanted to kind of think about. You know what are the challenges with the regulatory framework work around this I know, having been at an institution. Sometimes it’s hard to be able to have the resources to have home health nurse help with research, for you know, any kind of mobile units, for you know, blood draws, or anything like that. because, you know some institutions it’s hard for their investigators to be able to delegate authority to those things in a clinical trial, so it’ll be interesting to see how the regulatory landscape changes to accommodate this, because I think this is something that it’s going to have to be a little more flexible. And I’m specifically talking about. You know the thought of being engaged and not engaged in a research, and who is and what they have to do in order to be engaged.

00;09;12;09 –> 00;10;10;15

I think you’re hitting the nail on the head here. Some of the policy things are going to have to change, how they change will remain to be seen but the one big one hurdle that comes up often, let’s call it that is the oversight of the principal investigator. And how do you do that now versus when I was at a site I think I left there in 2007. There was No, I don’t think there was an iPhone. Maybe there was an iPhone, but then we, you know there were no systems like that where you could even think that you could do research differently. But now the clinical trial landscape involves home health nurses, involves potentially a retail pharmacy, involves remote screening. So how can somebody oversee that appropriately and that’s really the goal of PI oversight and again, for mainly US Environment. But the 1572 sort of the details, how what the expectations are, and what a principal investigator agrees to. Well, some of that now is not as clear cut.

00;10;10;15 –> 00;11;00;11

When everything happened in your research site. It was clear that you would have oversight of who was entering the data, how they were entering the data, whether you knew about adverse events or not on time. What are you manage those appropriately or not? Now, with different people coming in from all angles sometimes people that you may not have contractual agreements with. How do you oversee somebody that you have no way of overseeing in some way? So that’s some of the work we’re doing at Medable is trying to understand that, and maybe create a sort of we did a survey. We’re going to have a meeting about this to sort of think through what is appropriate oversight mean now that maybe we’re not all located physically, but we’re still all working on the same trial with the same participants and all of that. Another policy angle is sort of ethics review of DCT trials.

00;11;00;11 –> 00;12;25;10

So regular brick and mortar trials typically is like one month Review. Sometimes, you know, if you missed if the IRB agenda was full this is what I experienced some time in the month of May I had to wait till June to get my trial reviewed. But basically, you kind of knew what the timelines were. In a DCT it’s a little. It’s become a little different. We understand because it’s not always clear what elements are really digitized in these new trials and how that’s operationalized. And those are some of the things that IRBs need to know about. So we’ve worked with the MRCT Center at Harvard to sort of go through the whole patient journey and identify if you have a eConsent, you know, what would you need as documentation for then the IRB to have the appropriate decisions and to not overreach. So those recommendations are going to be coming out in, probably, but the second quarter of the year. But it’s really about equipping ethics committees, and IRBs with the right things to ask for asking the sponsors and the and the PIs to submit it in the right way so they don’t have to go dig in a consent to figure out if something is an electronic consent, or if it’s actually paper and things like that, and then creating some standards around that, so that the quality can be ensured. There’s no overreach but the appropriate conversations are had to ensure that patients’ safety and integrity in the trial are maintained, and that’s oftentimes about privacy and data security. So we were working on some of those things. Yeah.

00;12;25;10 –> 00;13;09;29

I love that you mentioned that because that is exactly some of the things as an IRB that we worry about. You know we want to know how the data is going to be secure. But also I love the idea that you are giving some guidelines, because not all IRBs are really familiar with what kind of security methods are out there, or what even kind of electronic tools are out there to be used, and what is secure and what is not. So I think that is something that IRBs really worry about a lot, and you know part of the review process, as you said, is to look at the consent process and to look at the data and where it goes, and what happens to it, so that they can make sure that the participants are informed, and that that’s part of the decision of the risk of the study.

00;13;09;29 –> 00;14;10;19

Yeah, we had some really interesting discussions, because, while sort of MRCT and Medable sort of facilitated the discussion, this was really a multi-stakeholder group of people representing IRBs at academic centers, Advarra was represented. They were industry sponsors represented, there were patients that were there, there were sites, so that we could really think of this from all angles, and come up with recommendations that were sort of based on a multitude of opinions and stakeholders, and that really sort of maybe create a path forward for how people can approach this like what is the intake form look like when you submit a decentralized trial, because it probably needs to have some extra little things that yes, check if it’s, eConsent, check if it you’re using televisits, and then to have the appropriate discussions. It was actually super interesting. I learned a lot. We had regulators there. We had representation from FDA and OHRP so we feel that well, the group came up with is might hopefully be a valuable tool for others to use.

00;14;10;19 –> 00;14;19;04

I love that, that is that is great, and we, as an IRB, will be really enthusiastic to hear about some guidance on that as well.

00;14;19;04 –> 00;14;21;12

Well you helped create it, so it was good.

00;14;21;12 –> 00;14;34;09

Yeah. So I wanted to explore Pamela what your thoughts are about, what populations, you know, are really going to struggle with DCTs, and what populations is it really going to benefit, or can we really tell yet?

00;14;34;09 –> 00;15;07;01

My one comment would be that we can’t make assumptions about populations. I think the EMA paper that came out a recommendations paper on these decentralized clinical trials did say that you have to really look at the populations at hand to make sure that this works for everyone the study populations, because, for example, you might consider that some elderly people might have a harder time with, you know, digital tools. But there’s plenty of older people that have no problem with that whatsoever.

00;15;07;01 –> 00;15;53;27

But there might be other things to consider such that maybe some populations would be better served using their own phone because they’re familiar with it, and they wouldn’t have to learn a new tool, so to speak. But if you only ask people to use their own phones, A. some phones may not work for the clinical trial, For example, My dad, when he was alive, had a flip phone. You cannot do any co assessment on a flip phone, no matter how hard you try. But then some people might not have a phone. So then you exclude people. So it’s this conversation about bring your own device versus provision devices. So bring your own device might be easier for an older population. But maybe some of those older people don’t have a device, and then you still have to provision devices. So it’s really an assessment of what it is they would be using it for.

00;15;53;27 –> 00;16;33;11

Then the condition itself sometimes, maybe for Parkinson’s you might want to make some accommodations. If people have a harder time, you know, working with smaller like, have motor movement issues. So I think all it’s just really not taking it for granted and going through the EMA paper also outlined vulnerable populations to maybe consider differently and pediatric populations, right. To sort of think of all those things, and just not make assumptions, and maybe start with a small feasibility study or an assessment, or maybe a literature search to make sure that what you’re trying to do has been tested, and you don’t make the assumptions that it’ll work in that population.

00;16;33;11 –> 00;16;54;13

You know I live in the South and in the South there’s a lot of distrust with healthcare and

a lot of folks won’t even go into the doctor. And so I think you know, getting that population might take some creativity, and it might be just the right thing for something decentralized, because they may not want to actually come into an office and see anybody.

00;16;54;13 –> 00;17;11;03

And then it goes back to what you mentioned earlier, which is working with those local communities to understand what it is that would make this work in the populations that we would want to make sure are represented in the trial because they might be disproportionately affected by the condition that you’re studying.

00;17;11;03 –> 00;18;03;15

I guess of what I would say is none of these solutions are by themselves a silver bullet. It’ll take a tapestry of things to make clinical trials better. Technology can help. Yes, we have to work with communities and patient groups to make sure that what we’re trying to do as far as a clinical trial works, and that there that we consider their concerns and their things upfront, because if you don’t, you’re going to notice it in lower recruitment rates right. the technology has many benefits, may have some drawbacks, but those can be helped. If you then also include the communities in which you work. Talk to the patients that you may want to consider and just put all that together upfront, and you should be able to end up with a trial that accomplishes what it plans to do, which is, try to understand whether treatment is safe and efficacious in the population you want to study the treatment.

Chapter 3: Patients First

00;18;03;15 –> 00;18;26;02

I love that, and I loved it, You know, over the past 10 years plus, a lot of medical centers have been looking at participatory research within the community. You know, how do you get the community engaged in research. And how do you get them to help you design researchers have input, on it. So I think what we didn’t know 10 years ago was we were really laying the ground where work for some DCTs.

00;18;26;02 –> 00;19;13;00

Right and some of the recommendations that CTTI wrote a couple of years ago and recently updated. Say that you know you need to involve the stakeholders, so you need to involve the sites you need to involve the patients and the communities and the investigators, and just make sure that your trial is set up in the best way. Because if you start off with a bad, you know a less than optimal trial, let’s say DCT technologies isn’t going to sort of magically make your trial all better. It’s not a magic wand, DCT elements work best in an optimized clinical trial for all the things like using quality by design focus on the data that matters focus on the things that matter, watch the things that are critical to the success of your trial and use the technology where it makes sense.

00;19;13;00 –> 00;19;29;02

Absolutely, I would agree. I think we’ve come to a conclusion that hybrid is going to be best and really choice of what, to what, how to design it is going to be best, and really allowing the participants to be able to have a voice in that as well

00;19;29;02 –> 00;20;32;17

Correct, I mean in the end, the participants are the experts on living with the disease, and therefore then also deciding what studies they want to participate in, because that’s the other part right. There’s a lot of studies, and oftentimes patients now will make conscious choices about the trials they want to participate in, and if they don’t work in their daily lives, for you know, maybe logistical reasons. If they don’t work in their life because of the science isn’t what they’re interested in, or you know all those things then we will continue to see low enrollment rates. But The Regulators needed to approve something to make sure something is worth. You know every medical product has side effect, so you just have to make sure it has more benefits, a whole lot more benefits than the side effects.

00;20;32;17 –> 00;20;41;02

Patients have to decide what treatments they want, and physicians have to decide what they might want to offer their patients. So we all need this data to be as reliable as possible.

00;20;41;02 –> 00;20;54;07

Absolutely and as transparent as possible. Well, thank you, Pam, for joining me in this important discussion on DCT and regulatory changes. I’m so happy we’re able to connect and really appreciate your perspective.

00;20;54;07 –> 00;21;04;24

Thanks so much for having me, Julie. It was a great conversation. I think we could talk for hours, if not days, about these topics, so look forward to the feedback we’re getting, and thank you.

00;21;04;24 –> 00;21;22;04

Absolutely. Thank you all for listening. If you enjoyed today’s episode keep a look out on Advarra’s social channels and on advarra.com for our next discussion.

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