Hannah Daniel (00:06):
Welcome to MedTech Connect, a new digital Health Regulations podcast from Citeline. I'm your hostHannah Daniel, and I'm a US regulatory reporter for MedTech Insight. Every month we'll interview aregulatory expert in the digital health industry who will help us break down policies and guidances
coming out of the FDA as well as other hot button issues such as cybersecurity concerns, the rise of AI
and ML, or the fight to protect medical data. New episodes published monthly, so be sure to follow
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MedTech Connect episodes come out.
In this episode, I speak to three experts at Hogan Lovells about the food and drug administration's
recent draft guidance on decentralized clinical trials, which we also refer to as DCTs in this podcast. So
the firm works with many companies who run clinical trials and the four of us sat down to discuss the ins
and outs of the draft, what pieces of the guidance still might need clarification and how they expect tosee the industry change as a whole. Now that DCTs are becoming mainstream, they also provide somehelpful advice for companies looking to run DCTs.
Kristin, Blake, and Stephanie, welcome to the podcast. I'm really excited to have you all here today totalk about decentralized clinical trials. But before we start, would you guys please introduce yourselves,
talk about who you are and maybe how you got into your position?
Kristin Zelinsky Duggan (01:28):
Sure. I'm Kristin Zelinsky Duggan. I'm a partner in the FDA medical devices practice of Hogan Lovells. I'm
based in Washington, DC. I have a background in biology and economics and so I started out in the
consulting world working with medical device companies, trying to get through FDA and then moved
into being a lawyer and generally work with companies that are making innovative products and trying
to help get them on the US market.
Blake Wilson (02:00):
My name is Blake Wilson. I'm a partner in the FDA regulatory group at Hogan Lovells as well. My practicefocuses on FDA's pre-market approval process across medical products including medical devices as well
as oversight of clinical trials. So a lot of my time is actually spent with sponsors of investigational
products with respect to study design considerations and the use of clinical data in FDA-relatedmaterials. And prior to becoming attorney, I worked in clinical research at Brown University and I also
hold a master's in biostatistics that I use to help navigate sponsors through the FDA regulated clinical
trial space.
Stephanie Agu (02:40):
Hi, my name is Stephanie Agu and I am an associate also at Hogan Lovells and I specialize in FDA
pharmaceutical and biotechnology development, and within that practice I work on a variety of issues
from exclusivity concerns to clinical research, bioethics, drug marketing and advertising. And I entered
this practice just because I had always been interested in government approaches to healthcare andsociety. And, on that note, it's been a fascinating few years in the FDA world certainly, and I'm excited to
discuss this topic with you.
Hannah Daniel (03:14):
Yeah, thank you guys for introducing yourselves. Really cool to hear a lot of bio background. I'm also aformer, I was going to say retired bio major, but you never really retire out of bio, but it sounds like thisguidance is really important to your work and the work that you do with clients. So we're just going tojump into the meat of it. So first I wanted to ask you all what about the draft was surprising? What was
expected? Did you feel like anything was missing from the draft?
Stephanie Agu (03:43):
Sure.
Blake Wilson (03:44):
This is Blake. I'll kick us off here. And I would say when the draft was issued, I actually thought that it
was pretty much in line for the most part with how I thought FDA would step into formally putting out
guidance in the decentralized clinical trial space, specifically follow the experience under the COVID 19
enforcement discretion policies related to clinical trials. I think FDA had a lot of time to actually consider
and weigh its options and how to implement the procedures for decentralized clinical trials. And I thinkthat you see a lot of those tactics utilized in this newest guidance document.
I would say one thing that I was hoping that would be there that wasn't discussed very much in theguidance document was actually around adverse event reporting. When you utilize ADCT format forclinical trials and specifically around more guidance on exactly when you use an HCP to collect adverse
events, how that should reporting should be conducted in order to make sure that it's generalizable withthe rest of the study data, and that all adverse events are being collected because I think that this is a
critical point and could create issues down the line when you actually are putting in the marking
application. So I was hoping that FDA would weigh in a little bit more on that, but I didn't see it here inthis guidance.
Kristin Zelinsky Duggan (05:12):
Yeah, I think that makes a lot of sense and I agree. I don't know that I was particularly surprised by anyof the elements that are outlined in the guidance, but I will just say that my overall impression, and I
think we'll probably talk about this a little bit more later, was really sort of how are people going topractically achieve this? It seems like a really sort of a tremendous logistical burden.
And as I was reading through, it was sort of like these are good ideas, but it seems like it would be a lotof work to do a fully decentralized clinical trial. And so it was really, and perhaps putting a lot of theburden on PIs to handle some of those logistics. For example, working with local sites or local healthcare
providers. I know that sponsors are very sensitive about putting more burden on PIs than they need to.
Obviously doctors are often very busy in their lives and usually sponsors want to take away a lot of thatburden. So that was just one thing I noted as I was reading through the guidance.
Hannah Daniel (06:16):
Before we go into some advice for companies, how do you guys expect to see clinical trials change overtime now that we have some kind of formal guidance in place?
Kristin Zelinsky Duggan (06:26):
Yeah, this is Kristen again. So I think that there are a number of things that can be implemented and anumber of aspects of the guidance that could be implemented. Perhaps I'm more on the skeptical sidefrom having done this for many, many years. I've seen FDA put out a lot of policies that really soundgood in concept and then don't necessarily come to fruition. So I think it remains to be seen how
sponsors will implement this, whether they will primarily take a hybrid approach and sort of takeaspects of decentralized clinical trials, which they're already doing as Blake noted today in the wake of

COVID and remote visits and things like that that have already been happening and use of digitaltechnologies and trials and take sort pieces of it or go to the fully decentralized clinical trial.
So I think that remains to be seen, but some of the benefits that I think they're hoping to achieve thatsponsors would hope to achieve too from the guidance are things like greater subject participation,
being able to enroll more subjects, more diverse subjects, subjects that might not be closer to majorclinical sites and possibly even sort of just retaining subjects better in trials, perhaps coming to a central
site at the beginning of the trial, but then being able to visit their local healthcare provider for follow-up
visits.
Kristin Zelinsky Duggan (07:44):
So perhaps increasing follow-up in trials. I think also the use of alternative data sources, the digital
health technologies, is obviously something that there's other guidances as well about that specificallyand use of electronic health records, but really collecting things in a much more modern way thannecessarily has been done to date.
Blake Wilson (08:05):
I definitely think there's going to be a lot of challenges here, but I think within my practice and thesponsors I've been advising on this, we hear a lot of excitement about the possibilities of decentralized
trials and one of, I think the key aspects is Kirsten was indicating around enrolling the broader
populations, but also being able to potentially speed up enrollment basically to pull everyone from asingle large center in the surrounding area and really being able to go out into more communities to beable to leverage those different pools of patients that may be available, and that this would actuallybring in a broader perspective from the patient population and give you a more robust, hopefully, data
output.
So I think companies are really excited about the potential enrollment opportunities. I think that you'll
companies trying to use this with respect to, again, not having to have everything focused within a single
site, coordinating all the subjects to come back within that location and instead giving more flexibility topatients to participate in clinical trials by allowing them either to have assessments performed at homeor to visit a clinical center or an HCP that is within a shorter distance to their home and allow that more
facilitative process.
And so I think the hope there is that you may actually just encourage more patients who would nototherwise think of participating in clinical trial to now become involved. So I definitely think that using
decentralized clinical trials is going to become a mainstay of how clinical trials are run, but the extent towhich is implemented is going to be the question mark, and we'll just have to see how well sponsors areable to manage it and how well PIs are able to manage this new scope of responsibilities when you haveadditional participants that are going to be involved in the management of clinical trials and actuallyproviding assessments.
Stephanie Agu (10:04):
I have one thing I wanted to add here as well, and this is Stephanie. To Kristen's point about in thecontext of diversity and greater diversity, I think something to mention here is that we often think aboutclinical trial diversity in terms of patients, and I think certainly DCTs do lend themselves to increasing
patient diversity, but I think also there's a potential for DCTs to also diversify the trial staff and personnel
involved in clinical trials. I think one of the features of DCT is being that those living in geographic areas
outside of your typical academic medical center can become more involved in clinical research. The
guidance speaks often about the use of local HCPs in clinical trials, and so I think that is a route that canbe used as well for us to see greater diversity in terms of clinical trial staff and other entities involved inclinical research.
Hannah Daniel (10:54):
Yeah, absolutely. We've done a lot of stories over here at Medtech Insight talking about different
companies and how they're working to increase diversity in clinical trials a lot of times using hybrid
clinical trial models. But yeah, some interesting conversations I've had recently around how do wediversify the staff as well and how do we educate people who are running these clinical trials so that theaccess is not just given to the patient.
I hope you're enjoying this episode of MedTech Connect. If you want to hear more podcasts like this,make sure to follow Citeline on SoundCloud, Spotify, Apple Podcasts, or Google Podcasts to be notified
about the newest episodes. Also, don't forget to check out our daily news publication Medtech Insight at
Medtech dot Citeline.com for all the latest on medical devices in the EU and US Again, that's Medtech
dot Citeline.com. Now back to the episode.
So a lot of promising things that are coming with decentralized clinical trials being popularized andcoming into the mainstream, but let's also talk about some concerns, and something of note is how
decentralized clinical trials are going to go through the inspection processes. So what concerns do you
have about how these decentralized clinical trials? Will be quality controlled?
Blake Wilson (12:21):
This is Blake, and this is a really great question. I think everyone recognizes, in theory, decentralized
clinical trials sound great. The reality is though that the devil's in the details of how it's actually being
executed. And so I think you'll see throughout the guidance document that FDA issued, one of theirconcerns that they raise, and it's a natural aspect of ADCT, is that there's going to be more variability
involved because you just have so many more people participating in the trial in terms of who's
conducting the assessments, who's reporting the adverse events, and how they conduct each one ofthose procedures. The benefit of a centralized trial is that you're going back to the same place. Usually a
set staff member is conducting those procedures, and so you have a lot of consistency from patient topatient. Once you start to enter into a either hybrid or a fully decentralized clinical trial, all of a sudden
you're adding more and more variability into the process.
And so that creates the possibility that people are going to conduct study procedures in slightly different
ways that could potentially introduce bias, and this is one aspect of the inspection. It's going to become
very important because FDA is going to be looking for those sources of variability that exist and may
have skewed study results. And so that is I think, one concern from the inspection standpoint.
In addition, simply the ability to monitor decentralized clinical trials can be very challenging within acentralized aspect. You have a limited number of sites. You can set up monitoring visits on regularschedules. You check to make sure informed consents are being conducted correctly, spot checkthrough the data, and it's a well-established procedure for how you do that. When you start to moveinto decentralized clinical trials, though, the ones to actually manage and monitor all these different
participants who are helping to conduct your clinical trials becomes much more challenging from alogistical perspective.
I think FDA tries to be very clear that the onerous is both on the sponsor to be monitoring the clinical
trial at the high level, but on the PI level, they're also going to be in charge of managing anyone thatthey're delegating responsibility to. And so essentially, whenever you're creating the opportunity formore people to be involved, again, you have this opportunity for more variability to be introduced or for
people to not perform the study correctly. And so monitoring is going to have to be a key aspect of howthis is being performed and making sure there is significant coordination between these different groups
in order to make sure that the study is being run in a scientifically valid manner. So again, you're going tohave to make sure that you have ample training upfront. All these aspects I think are going to become
very important.
Kristin Zelinsky Duggan (15:13):
Yeah, no, I think you really covered it, Blake, and I would just add that in addition to all the different
players involved and all the different entities involved, devices involved as well, the various monitoring
devices, the ways that the data is collected and how it flows, how both for the sponsor when they're
monitoring the study, but then also for inspectors, how they're verifying that all the data that may be
coming from a wider range of sources really is valid and appropriate and that there's sort of a chain ofcustody of that information. And I know that's also covered in a different guidance, but the DCT
guidance that came out covers that as well. Another source of variability, I think in the trial that you
were talking about.
Stephanie Agu (15:58):
Well, I think one thing to mention, which the idea of where inspections can take place, and so there is acomponent in the guidance that mentions that FDA will inspect the central location and the central
locations where all of the trial related records are kept and stored. But it's important to remember that
FDA has expanded inspectional authority to really inspect any sites, facilities, and persons involved in or
who have engaged with the sponsor in terms of data collection and data analysis for the trial. So eventhough there is a central location where all of the records will be stored, and that's definitely up for
inspection, it's important for sponsors to keep in mind that there's really wide variety of different
entities involved in a trial that can be inspected as well.
Hannah Daniel (16:45)
It seems like there are some concerns and there's a lot of variables, and maybe those will be addressedin a final guidance. Maybe those will be addressed in the field, but for companies who are starting to dip
their toes into DCTs, who are already full steam ahead on them, for people who are unsure, what advice
would you all have for companies who are interested in running a decentralized clinical trial?
Kristin Zelinsky Duggan (17:08):
This is Kristen again. I think one of the things is to really plan for all the logistical challenges that we justtalked about. There's a number of considerations in the guidance, figuring out the roles andresponsibilities of the sponsor and the investigator who's doing what, who's responsible for supervisingwhom, making sure you have plans for monitoring plans for ensuring the integrity of the data. I think
there's probably going to be a lot of having to develop procedures and SOPs that maybe would beoutside of the standard ones that companies would already have for clinical trials. I think another thingis talking to FDA as they put in the guidance and as we sort of always recommend talking to FDA when
you're planning your trial and certainly getting their buy-in and their thoughts on the trial design andhow you're planning on conducting it could be helpful. And then this is sort of basic, but whether or not
the format really lends itself to your trial, I mean for many kinds of medical devices, implants and otherthings like that, it may just not be all that practical to do. For example, a fully decentralized clinical trial.
Obviously you couldn't really do that, but which aspects from this guidance might make sense in the trial
and for what kinds of devices it may be appropriate for versus not.

Blake Wilson (18:25):
And I would advise sponsors to be very careful about the assumptions that they're billing into theirclinical trial design when they're trying to incorporate a decentralized format. And a lot of that comes
down to really thinking about how transitioning from a traditional centralized trial to a decentralized
trial could have an impact. And this includes on things like sample size calculation and effect size. If
you're using data that is from a centralized clinical trial, in order to establish what you believe a likely
effect size for your product is going to be, you need to take into consideration that decentralized trials
naturally have more variability and that this will impact what your sample size calculation would be.
In addition, we were referencing digital technologies for remote monitoring and assumptions that may
be built in about what validation was necessary to establish the validity of that product for use in aclinical trial, and making sure that you reach out to the FDA before you start to run the clinical trial.
These issues are extremely hard to address after the fact and may become a huge hurdle in order to getpast a marketing submission.
Stephanie Agu (19:36):
Then on that note, the comment period for the draft guidance is still open. It'll be open until August 1st,
so we expect to see many members of the industry submit comments and see if FDA will incorporate
them in the next final guidance.
Hannah Daniel (19:50):
Well, that was a perfect way to wrap up, so I wanted to thank you all for being on this episode ofMedtech Connect and sharing your thoughts about the decentralized clinical trials guidance.
Blake Wilson (19:59):
Thank you.
Hannah Daniel (20:00):
Thank you so much for your time.
Kristin Zelinsky Duggan (20:02):
Thank you.
Hannah Daniel (20:07):
MedTech Connect is a podcast by Citeline. If you'd like to learn more about this topic, check out
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Note: This transcript was generated with the use of AI.