“Our biggest competitor is paper,” Andrea Bastek, director of innovation at Florence Healthcare, tells me. “I speak to software developers all the time who say [this],” she explains, “and I talk to people in the clinical trial space [who] say, ‘paper works great.’” Only, as Bastek well knows, it doesn’t. Running through a hospital, paper in hand, trying to track down a doctor for a wet-ink signature is hardly an efficient way of working. Nor is archiving medical records in rooms full of ring-binders or sending trial monitors halfway across the world to check on something they could just as easily have seen on a video call.
“The goal is for clinical trials to go faster and be more efficient, so that we get new drugs and devices to patients and medical professionals as fast as possible,” Bastek explains. “[But] there are a lot of things standing in the way of that goal.” Many of these challenges are related to time expenditure, like the time to develop a protocol, get regulatory approval and funding to run the trial, as well as selecting sites that have the right patient population and expertise. But there’s also the issue of recruiting the patients themselves and keeping them onboard so that the data is complete.
As if these constraints weren’t enough, clinical trials are also faced with “overarching issues of inefficient workflows, lingering paper processes, and technology that does not integrate”. And that is where Florence steps in.
“At Florence,” Bastek explains, “we have the goal of giving sites their day back from paperwork, so they can do the important work of advancing clinical trials. We offer eRegulatory and eConsent products to reduce paper and create efficient electronic workflows that also benefit the sponsor by making remote access possible and easy.” It sounds like a simple solution – but in the regulated world of clinical trials, Florence’s work is critical. “It does sound so ridiculously simple,” Bastek agrees, “but the clinical trial space is just so highly regulated, it’s so far behind the rest of the medical field.”
Change of pace
The introduction of technology like this into the clinical trial space has been growing gradually over the past ten years – but in the past two, the pace of change has visibly gained momentum. “I would say the rate of change from ten to five years was very slow; and from five years to one year was not much faster. But then Covid-19 really accelerated everything. Covid was such a catalyst for clinical trials. People would never have done the things they’ve done in the last two years had it not been for a global pandemic.”
The development of advanced technology, coupled with the circumstances of a global pandemic, has had measurable impact on clinical trials. Now, thanks to companies like Florence, workflow is beginning to be streamlined, so that physicians and investigators can spend more time on the things that really matter: patient recruitment and communication. Yet, as Bastek acknowledges, while efficiency gains are critical, they simply aren’t enough on their own to offset the innate difficulty of conducting a trial for a low-prevalence disease. “In rare disease trials, all of these challenges are amplified” she explains. “There are fewer specialised physicians for each rare disease, which means less possible clinical trial sites; there are less potential subjects to recruit and they are likely [to be] more geographically distributed, which means many won’t be close to the small number of clinical trials sites.” Increased geographic distribution means that there are more regulations to be considered, both on a national and regional basis. The limitations of studies that serve such a small population are numerous, and include sponsors being less inclined to fund them, as well as recruitment often taking place over a long time frame in order to have a statistically significant data set.
With all of these challenges to face, rare disease trials need more than a technological band-aid. As Bastek recently observed in an article for MedCity News: “Technology can help rare disease clinical trials by making it easier for sites to find patients, share data, and run studies. But technology alone won’t overcome the challenges […] We need to embrace a variety of strategies to serve the millions of people waiting for lifechanging rare disease treatments.” One such strategy Bastek suggests as a potential game changer in the rare disease trial space is genomic sequencing. “When people think of advanced technology,” she says, “they’re often thinking of AI. And, you know, if you can do genomic matching – that sort of advanced technology really will help when you’re talking about low-prevalence rare diseases.”
“One of the real challenges in rare diseases is that it is expensive to run the trials and that translates forward into expensive therapies that the health system is reluctant to adopt.”
Mark Caulfield
Reality check
In the UK, genomic sequencing is becoming a reality. In November 2021, the ‘100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care – Preliminary Report’ was published – and the first findings are already revealing just how transformative genomic sequencing could be in rare disease diagnosis and treatment. “One of the real challenges in rare diseases,” explains professor Sir Mark Caulfield, a primary investigator on the pilot, “is that it is expensive to run the trials and that translates forward into expensive therapies that the health system is reluctant to adopt. So, we need to improve the opportunity cost of these trials. One way of doing that, which we’ve set out to do in the 100,000 Genomes project, is to create a resource where, based on informed consent, you longitudinally live-course follow people, right up until after their death. You have the ability to concentrate all their electronic health data, alongside their genome, so that you can research on the disease of interest, but also on other things that turn up in that data.”
In other words, genomic sequencing is far more than just the next technological add-on; this research really does have the potential to transform the rare disease clinical trial as we know it, at a structural level. “What if,” Caulfield asks, “from a national genomic medicine service, you could have your entire nation’s rare diseases – which have been through your diagnostic investigations – there with their data (or as many as consent), and that is then your sampling frame?” Not only would this help “address the major block, which is that it’s difficult to enrol people for rare disease trials”, but it may mean that the clinical trial becomes a more prevalent part of life, even from infancy. “In rare disease, if you had such a platform […] in early life, perhaps in the newborn period, where you could detect these diseases when they’re fully penetrant,” Caulfield explains, “then you would be trialling your therapy not simply after someone has got a series of fixed deficits that you can’t recover, but at the earliest possible stage.”
“Country-specific regulations are often outdated, based on paper models, and vary from place to place. It isn’t one software company that’s going to be able to achieve that – but there are organisations working on it.”
Andrea Bastek
Caulfield’s prospective model seems almost utopian, yet it does reveal one of greatest hurdles that the rare disease trial has yet to overcome: for now, a genomic medicine service like this would have to remain a national, rather than global, enterprise. For rare disease trials, some form of international consensus “will be necessary”, Bastek urges. “In order to get the data needed to show the success of new treatments [and to] reach more patients with a rare disease so that enrolment is faster. However, this raises huge regulatory and data privacy challenges. Country-specific regulations are often outdated, based on paper models, and vary from place to place. It isn’t one software company that’s going to be able to achieve that – but there are organisations working on it.”
The Global Alliance for Genomic Health is one such organisation, aiming to create, as Caulfield explains, “national data assets that can be linked together through electronic methods such as application programming interfaces, [which] connect assets. So, the data asset doesn’t leave the jurisdiction, which means it complies with laws […] but there is information sharing. And that information sharing allows access to data in a way that you don’t get from simply sitting within your own silos.”
Battle it out
At the end of the day, these questions will need to be battled out by national and global regulators and lawmakers, not by software developers and scientific researchers. But what is clear, from both Bastek and Caulfield, is that we need to be investing in technological solutions – from something as simple as an e-signature, to something as revolutionary as genomic sequencing – if the future of the rare disease trial is going to improve. Collaboration will be key, as Bastek emphasises, between sites and sponsors, between patients and physicians, between nations and regulators – and between different technologies. “In a utopian word,” Bastek says, “all software works nicely together, we don’t have [workflow] redundancies, and we can really get things done faster, we can reach more people.”
For Caulfield, the future holds the promise of early diagnosis and intervention through advanced national platforms. “What we need to do is to get the earliest diagnosis and earliest intervention, because we’ve got the greatest chance of modifying disability and adverse outcomes if we do that. I also think by having national platforms, [through] which we can access and recall patients for research, then we can do these trials much faster and much more affordably – and this will then make the medicine more affordable [for] the health systems.” What’s more, as Caulfield says, “we are entering an era where – whether it be rare disease, cancer or any other trial – we should longitudinally live-course follow people beyond the end of the trial, because there may be late signatures of harm or signatures of benefit that are not captured within the finite period of the trial.”
The key, it seems, to advancing clinical trials for rare diseases, lies in a total shift in perspective – the kind of shift that only technology can bring about. With Florence’s digital software, then, we can start to think beyond the constraints of space and site. While, with genomic sequencing, we might even begin to surpass the limitation of time.
