TRANSCRIPT
Deborah Borfitz:
Hello and welcome to the Scope of Things podcast, a no-nonsense look at the promise and problems of clinical research based on a sweep of the latest news and emerging trends in the field, and what I think is worthy of your 30 or so minutes of time. I'm Deborah Borfitz, senior science writer for Clinical Research News, which means I spend a lot of time with my ear to the ground on your behalf, and a lot of hours every week speaking to top experts from around the world. Please consider making this your trusted go-to channel for staying current on things that matter, whether they give us hope or cause for pause. In another five minutes or so, I'll be speaking with Doug Bain, founder and consulting partner of UK-based ClinFlo, about his proposed regulatory blueprint for digital trials. But first, the latest news, including a tool for detecting fraud and sampling bias in decentralized trials, automating the transfer of clinical data into trial platforms, technology for identifying potentially dangerous drugs before the start of trials, a novel women's health and menopause initiative, the possibility of a regenerative therapy for spinal cord injury, and a new oral treatment for preventing dementia.
Deborah Borfitz:
Researchers at the Medical University of South Carolina have produced a set of tools designed to detect fraud and monitor for sampling bias in decentralized clinical trials while making the data collection process easier for study participants. The cheat blocker tool helps to detect fraud during the early stages of a trial by checking for duplicate screening submissions, while the quota config tool watches for key characteristics during screening to ensure a representative sample is enrolled. A third My Trials tool provides a streamlined process whereby participants can use a single smartphone app to record and securely submit multiple biomarkers from home. The ultimate plan is to make the entire platform available to scientists around the world. The Mount Sinai Tisch Cancer Center has become one of the first big name research institutions in the U.S. to automate the transfer of clinical data from its electronic health record system into clinical trial platforms. The new capability is powered by Ignite Data's Archer platform and integrated with Epic, and early pilot testing showed reductions of up to 70% in manual transcription time, improving both data quality and workforce efficiency. The real-time data integration tool, initially being used in oncology, also allows oversight bodies to review aggregated safety and trial data sooner, helping to identify trends, hasten response to potential concerns, and accelerate decision making during the development of new therapies.
Deborah Borfitz:
To contend with one of the major reasons for failures in new drug development, researchers in Korea have built a machine learning-based technology that learns the differences between animals and humans to preemptively identify potentially dangerous drugs before the start of clinical trials. They looked at the genotype-phenotype difference between cells, mice, and humans in terms of how genes targeted by drugs function, focusing on the gene's perturbation impact on survival, the pattern of gene expression in different tissues, and the connectivity of genes within biological networks. The AI tool demonstrated predictive power significantly better than reliance on drug chemical data alone and existing state-of-the-art models, as well as the ability to alert users to drugs facing market withdrawal due to toxicity.
Deborah Borfitz:
Tufts University is launching a women's health and menopause initiative, a first of its kind academic collaboration uniting expertise in its schools of medicine and nutrition with the renowned Tufts Medicine Health System. A $4 million gift is funding the initiative, endowing two inaugural professorships whose holders will serve as co-directors and drive an agenda intended to advance clinical care, education, and research in novel ways that improves women's health across the lifespan. Across disciplines, Tufts scientists will focus on longevity and healthy living. Research work will explore vascular aging, neurobehavioral health, diet, and chronic disease, and build a national menopause outcomes registry linking patient data, clinical care, and research. We may soon be seeing a clinical trial of a regenerative therapy for spinal cord injury thanks to researchers at University of California's San Diego School of Medicine who harnessed bioinformatics to fast track the discovery of a promising new drug known as thiorphan, previously tested in humans for non-neurological conditions. In adult human brain cells previously not possible to culture, it increased neurite outgrowth, a key metric of regeneration. And when combined with neural stem cell graphs and rats with spinal cord injury, it led to significant improvements in hand function and an increase in neuronal regeneration into the injury site.
Deborah Borfitz:
And finally, researchers in Denmark are investigating an oral treatment for the prevention of frontotemporal dementia, aka Bruce Willis dementia, in people at genetic risk of the degenerative brain disease. It is the most common cause of dementia in people under the age of 60, progresses rapidly, and at present has no approved treatments. The first clinical trial shows that the treatment, which is being developed by Vesper Bio, can normalize levels of the protein progranulin in cerebral spinal fluid and has a favorable safety profile in patients who have not yet developed symptoms of the disease. The next step will be a larger clinical trial involving symptomatic patients. As a reminder, links to the articles, studies, and press releases referenced in this month's news segment can be found in the show notes.
Deborah Borfitz:
It is now my absolute delight to bring in clinical trial data innovation veteran Doug Bain to talk about some of his recommended changes to the now outdated 21 CFR Part 11 regulation of the U.S. Food and Drug Administration related to the use of electronic records and electronic signatures. Thanks for joining me from across the pond, Doug.
Doug Bain:
Thank you, Deb. Very nice to be here. I'm happy to discuss something that I've probably been thinking about for 25 years or something.
Deborah Borfitz:
And we're going to try to cover it in about 20 minutes, maybe. We'll do our best. Okay. Well, since we're talking about regulations here and the ones in effect in the US, I wanted to start out by covering what call qualifies you to hold an opinion on such things and perhaps gives you a bit of professional sway. 20 years in, of course, is part of that. Could you please uh take us all on a quick journey of your career up until the recent launch of your consultancy?
Doug Bain:
Absolutely. So as you say, I think I'm I'm I'm referred to as a veteran. I'm not sure if that's a good thing or a bad thing. Um, but but it does mean that I've been working in this particular field pretty well full on since 1996. Um primarily I've focused on software. So I'm a tech guy. Uh so used to work at IBM, uh, worked on the ClinWare platform, uh, worked at Metadata, so I was uh one of the early employees at Metadata joining in 2004. Um but I've also developed my own platforms, so I developed a platform called Clinpal. Um I also had five years at a CRO, which was also very useful, understanding that side of things. Um but earlier this year I decided to branch out my own and uh form my own consulting company. And that's given me pause to consider where I feel things do need to change, not just obviously in the software side, but in how uh regulations help support and control um good and and bad uh technologies.
Deborah Borfitz:
Yeah, I'm sure it helped you appreciate uh a lot of the on the ground realities of end users as well. Is that all sort of part of your mission here? It seems to me that was what I was getting from you last we talked.
Doug Bain:
Yeah, I do feel strongly that that we do hold quite a lot of responsibility. I say we, you know, those involved in the technology development and technology use, we hold responsibility for the safe and effective study of of drugs. And sometimes I do feel that things are getting in the way. Um technology should be helping, not hindering. Um so I'm always looking at ways that can uh improve the experience of technology for sites and patients. Um and I think the way in which regulations have uh aged, if you call it, um has led to increasing levels of inefficiency, even um, in how we run clinical trials. And I just thought this time I put forward some ideas on how we can avoid it.
Deborah Borfitz:
Yeah, okay. Well, this is a good way to segue into a discussion about uh your strategy for turning uh 21 CFR Part 11 published during the early age of the internet into a more practical regulation that helps streamline rather than bog down clinical trials. Um before we dig into the particulars of your plan, which we're going to do, could could you give us a sort of the 10,000-foot view of your blueprint and what what sort of anchors it?
Doug Bain:
So, I mean, I think there's there's a few areas where um the actual application of the regulations they don't hold value. I mean, I I think ultimately uh if you were to speak to uh you know a chronic uh cancer, chronic disease cancer patient and say, you know, do you care about something like source data? Um they wouldn't. They they wouldn't see the value in it. And I think there's been quite a push on the last few years about risk-based. And I think some of the uh criteria that are defined in 21 CFR Part 11 don't really consider risk. You know, the definition of source or the use of cloud platforms, there's there's there's there's old um rules applied to new methods, and that they're not as efficient as they could be. So I I I've sort of thought through, based on my experience of developing my own platform, what would I like to see change that I believe would bring uh therapies uh more rapidly to market while not uh compromising quality and safety.
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Deborah Borfitz:
Well, I definitely want to hear, I know there's various pieces to this plan, if you will, and one of them is this idea of the trusted third party. Um can you, you know, tell me what would qualify someone to take on that role and how would trust in that entity be built? And as envisioned, would would every trial or set of trials have its own? I guess your TTP is what we call then the third trusted third party. You know, yeah. Walk us through, you know, what would that entail being a trusted third party and and what value does it bring to the table at night and where do the efficiency gains come from?
Doug Bain:
So so maybe it's probably best described more from the end-user perspective. So when you do when you do clinical trials, most typically the a sponsor will fund the technologies that are involved in that clinical trial. Um and as a sponsor uh funding the technology, generally they they almost own the uh the entity, the data that surrounds that. So they'll let's say it's an electronic data capture system, they'll license a system, you know, EDC system, it could be from Viva or Metadata or one of the other vendors. Um, and they then are the the sort of let's call it the key holders uh of the system. Um now what that means is that you end up with certain levels of inefficiency in that when you do a trial, instances of software are set up for the sponsor, um, and sites will be asked to log into these instances of software. Um now that's led to a few issues.
Doug Bain:
Well, first of all, uh as I'm sure sites will be familiar with, many logins, uh, because we're setting up an instance of software that's specific and controlled by the sponsor. Um and also they can't necessarily take their use of this EDC system and take it forward to other studies and other sponsors they might run with. So the sponsors each hold their own control over these instances, um, and it leads to terrible inefficiencies. So you can't uh typically carry forward maybe training, uh, you can't use single sign-on to the same degree, and so on and so forth. Um, what I would like to see changed is this idea of a trusted third party where all the different stakeholders can sign up and be, can have a light, can have an instance of this platform beyond the scope of a single study or beyond the scope of a single sponsor. So, you know, the way that might appear to a site is they sign up to, you know, uh ABC EDC platform, and they will continue to have an account on that environment for as long as they want, um and they will be able to apply that account to any trial or to any sponsor and be able to effectively reuse a login or reuse training um without uh the direct control of the sponsor.
Doug Bain:
Now that this goes further if you think about it from the patient's perspective. Uh the sponsor, if the sponsor controls this clinical trial environment, the uh patient's uh existence in that platform is limited to the existence for a single clinical trial. With the trusted third-party platform, what you have is you have an environment where patients and sites and so on can sign up to it. And at the end of the study, they can still, you know, potentially use that platform and potentially even have access to the data in that platform, maybe their data in the clinical trial. And they can sign up on the same platform for other sponsors and other trials. So the idea of trusted third party allows this instance to continue to exist beyond the scope of any individual organization or person because it's the trusted third party who controls that environment and manages the security and validates the security to ensure it always works. So that's the idea of it. That's the idea.
Deborah Borfitz:
Very good. Very it sounds brilliant and complicated, and we have a ways to go for sure. Um, and I also wanted to talk about another sort of piece of your puzzle, if you will, this proposed hypertrials designation. You know, what sort of speed gains would a sponsor realize by seeking that status as you've recommended, and and what might the FDA eligibility criteria look like?
Doug Bain:
Right. So this is I mean, the name hypertrial is not something that's that's out there. It's something, it's a name I've given to a set of uh particular approaches to running a clinical trial. Um, and the the overall idea is that it's more digital, it's less paper, and any of the processes that maybe still remain in order to support you know investigator-led studies, um, don't necessarily need to be um slowing down studies that may be able to run faster because they have the resources or or size or capacity to go faster. Um so I think if uh I'm sure people will be familiar with clinical trials that were uh run to support uh COVID vaccines, they ran very, very quickly. And it was almost despite the regulations. You know, they did follow the rules and regulations, but it was it was quite a difficult. There was a lot of dialogue, a lot of discussion, a lot of agreement between the uh drug manufacturers and the regulators to allow the studies to run in that particular way. Uh, we would like to make this a matter of course in uh provided you meet certain criteria, you can run on a high-speed basis. You have to agree to have integrated systems, you have to agree to run in a fully digital fashion, and so on and so forth. Um, and by doing so, you can speed up the overall process, both for the uh sponsors, but also for regulators gaining access to information.
Deborah Borfitz:
That all makes total sense. Um, you've been campaigning for a while now for the FDA to retire the term source in favor of authoritative data that is everyone's point of reference for a study. Why has this been such a hard fight to win? And have we inched any closer to that new day?
Doug Bain:
I wish I could say yes. Um the the term source is is just hung around. I mean, it's it's almost something that's unique to clinical research, and that uh for those maybe not familiar with it, you know, we have a special designation of source data where it's considered uh the point of reference um when carrying out clinical trials. So uh the place in which data is originally captured is called the source data. So if that uh data happens to be in a post-it note or a you know a pad of paper or wherever, that is the source data. And and in principle, according to the regulations, it's that source data that should be uh confirmed as being uh the the a match for the data that's entered into or transposed into an ECRF. Um so my my challenge there is that um that data may not be good or may not even be as as good as the data that's gone through an EDC system with edit checks and you know and dynamics and so on. So I would like to see uh uh a better uh support for uh what I've referred to as authoritative data, um, rather than simply always referring back to the original record of data. Because I believe I believe the systems are are capturing this data according to a protocol, according to uh relatively strict standards, validated standards, in many ways should be considered a a better representation of the data rather than whatever was scribbled out in a post-note.
Deborah Borfitz:
Yeah. Yeah, and the FDA, of course, has a new administration with its own set of priorities. How do your ideas square with what uh the new FDA commissioner and director of the Center for Biologics Evaluation and Research have publicly disclosed as their modernization plan?
Doug Bain:
Well, I think we're I would say we're on the same page. We're both trying to achieve the same thing. Um uh what I would like to do is is is certainly coming come at it from the industry's perspective, the technology industry perspective, they're saying, you know, here's some ideas for you guys, you know, this is where we are currently, we feel we are being slowed down. Um and if you were to, you know, accept these standards or um then I then I think we would we would move things forward. And you so I I don't want to be just ripping up the rule book altogether. I think there are very, very good reasons why the FTE exists and the uh rules and regulations that that support the FTE exist. I just think that we can move the bar a bit further forward because of new technology and you know the evolution of standards and so on. Um so I know I th I think we're on the same page, and I I I'm really just volunteering um some potential uh approaches that might improve my okay, very good.
Deborah Borfitz:
This all makes perfect sense to me. So let's wrap up with next steps on how you plan to test your hypotheses and where you imagine the FDA fits into this experimentation phase. What sort of case studies might we expect to see moving forward and realistically when and where could they happen?
Doug Bain:
So I think you know, the the idea of many of the uh the concepts, it it's actually not you. You know, I I was running clinical trials on tablets, uh capturing data as as source data into these tablets way back in 2001. So it's not that it cannot be done, it's just not considered the the gold standard. So I think we need to continue to go to the regulators, and uh, you know, I've pointed I've pointed the finger more at the FDA, it tends to be the general point of reference uh for clinical research. Um, but you know, I I'm in the process of reaching out to the EMA and other regulatory authorities saying, right, you know, how would you uh see these proposals? And I'm sure if we're looking at them, you know, it's it's close to what the EMA are looking for, the some of the regulations and improvements with risk-based approaches, uh, changes to ICH with the R3 release, they're all going in a similar direction. Uh I think as a case of just continuing to have a dialogue, speaking to the regulators and seeing, you know, uh whether it's actually a change or whether it's just a relaxation on the on how the the existing processes are interpreted. You know, I think that's what we need to be doing. We need to be speaking to the regulators more and pushing for these changes as soon uh you know sooner or later.
Deborah Borfitz:
Okay, very good. I love your vision with all this stug, and appreciate your tireless devotion to improving the throughput of clinical trials, as well as the experience of people participating in them, meaning both sites and patients, of course. Um, thanks for being a guest on today's show. And when you move the needle in any sense, please give me a call and we'll talk again. Sound good?
Doug Bain:
Love to talk about it.
Deborah Borfitz:
And as always, a big thank you to everyone out there for listening in. If you're not subscribed to this podcast yet, please consider going to Apple Podcasts and doing so right now so you don't miss your monthly dose of news and perspectives. You'll be hard pressed to find anywhere else. And if you're up for it, I'd also be so very grateful if you'd leave a rating and review while you're there. One final note: if you'd like today's show, it's only a glimpse of news and insights we have on tap for the next Scope event taking place in sunny Orlando, Florida, from February 2nd through the 5th, 2026, where, spoiler alert, Doug will be moderating a panel discussion on the great data capture debate, EHR eSource and traditional approaches. Two expert panels, one comprised of vendors and the other sponsors, will come together to provide a more holistic view on what truly matters from an operational and strategic perspective. Please plan to join Doug and me there, and be sure to use discount code SOT10 for a 10% discount off any current rate. For more information, visit scopesummit.com. Bye for now.