John Zibert, CEO of Studies&Me, dials into our virtual meeting from his home. “I’m in a big forest,” he says, “just north of Copenhagen. It’s been good during Corona, just to have walks around.” It’s something that’s been heard a lot over the past 18 months: more and more people migrating out of big cities to discover the virtues of working from home – however remote that may be. But it’s not an altogether new refrain; and it’s not only working that people have learnt to do from home.
For the past few years, clinical trial designers around the world have been working strenuously to make studies more remote, more decentralised and more virtual. The Covid-19 crisis might have created the perfect storm, but the systems and technologies that have made remote activities possible were in place long before the pandemic. “I wouldn’t say that everything was smooth under Covid-19,” Zibert admits, “but one thing’s for sure, it raised some awareness about this industry; it promoted us, indirectly. A lot of regulators suddenly saw that e-consenting, IP [investigation product] distribution to the patient’s home, and remote visits can be done.”
Zibert set up Studies&Me, Europe’s first virtual contract research organisation, back in 2015. “I had this passion for doing things differently,” he explains. “I felt that the way that we conducted clinical trials was a little bit too narrow and too little focused on the greater good of the patient. We just saw patients like a lab mouse that you wanted to treat. So, how could we make it even more personal?” Zibert and a team of four piloted a trial of fish oil tablets.
From their office in Copenhagen, they were able to run an entirely virtual trial, recruiting 60 patients in Canada through a prototype of Studies&Me. The study was a success, Zibert reflects, resulting in two things: “First, we could target, identify and recruit patients for the trials, and, secondly, we had a new operational model that would be completely centralised with respect to trial staff, but decentralised with respect to patients.”
Lead the way
Studies&Me is one among a number of spin-out companies from Danish organisation LEO Innovation Lab, including Noie, KlikKit and OMHU – all mobilebased technologies that have helped to push clinical trials on to the virtual stage. And while the Danish hub is blazing a trail in Europe, the US FDA is leading the way across the pond. The MyStudies app, another platform developed for use in decentralised clinical trials, was released by the FDA in 2018. As Leonard Sacks, associate director for clinical methodology at the FDA, explains, “The MyStudies app was a customised way that we could get information directly from patients themselves. It’s a secure mobile phone app that allows us to collect patient-reported outcomes sometimes used in clinical trials.” During the pandemic, he says, “The app was actually modified to facilitate trial electronic enrolment for patients who are in isolation and can’t use standard procedures for informed consent. So it was adapted to the Covid environment and it’s there for use afterwards.”
Yet, as Sacks is keen to stress, “mobile apps are related, but only to a small piece of what we’re really talking about, which is Digital Health Technologies (DHTs).” This term DHT, which the FDA is currently drafting guidance for, “includes a very broad swathe of mobile technologies”, Sacks explains, “including mobile sensors, mobile apps, and platforms for data acquisition, like cell phones and tablets.” Though there are a number of apps that help to diagnose, treat and monitor health disorders (take LEO Innovation Lab’s Imagine, which tracks treatment for skin conditions), mobile apps tend to be limited to patient recruitment – like Studies&Me and MyStudies – or informative resource platforms – like The Duke University Mobile App Gateway. As Ryan Shaw, faculty lead on the project explains, the Mobile App Gateway “is a resource for our community, where if you have questions about how to leverage mobile apps, wearable technologies, or digital health at large, our team helps to provide guidance on how you do that; how to select tools, how to select data, how that might be incorporated into a research process for a trial or to a care delivery”. In other words, as the name of the project implies, apps are a gateway into the world of DHT, but as Shaw notes, echoing Sacks, they’re “just one little piece of how data gets flowed and captured across the entire feedback loop”.
Nevertheless, mobile apps do remain an integral piece of the still-evolving DHT puzzle, helping to “democratise” virtual healthcare, as Shaw suggests. “I think that one of the biggest benefits is that this is happening across socio-economic backgrounds and across geographies.
“I felt that the way that we conducted clinical trials was a little bit too narrow and too little focused on the greater good of the patient. We just saw patients like a lab mouse that you wanted to treat. So, how could we make it even more personal?”
John Zibert
60
The number of patients recruited for an entirely virtual trial in Canada.
Studies&Me
“You don’t just have to have a computer to get access to these remote data collections. And now that we can collect data from people at almost any time and anywhere, it can be much more democratised,” he says. “We can tap into tools that allow us to capture data from people’s pockets or in their home, or in their car. Same thing for clinical trials – we don’t just have to have zero months, six months, 12 months, we can capture all day long, any day. That can be excessive, but it creates brand new opportunities to have real insight into people’s lives and into what health really means. And I don’t think that can be overstated.” Along with the benefits, however, there are the inevitable obstacles and challenges, and people have to be aware of these if they’re going to make the most of DHTs. For starters, “it is extremely expensive”, Shaw admits. “But once it’s built it’s so scalable. There’s this really expensive curve at the top, but it really evens out and becomes much cheaper. It’s like any new technology within a society – it’s a lot more expensive for the early adopters.” And then there are data and privacy regulations. “Those are such critical concerns,” Shaw notes, “because it can be hard to figure out where the data is going. It’s not as simple as: it goes from a phone to a hospital. The data might go around the entire world – and the question is, whose servers is it going to? Is it a consumer device? And do you consent to give it to these third-party companies who can do whatever they want with it?”
A learning curve
When it comes to healthcare, developers have to work extra hard to make sure that these technologies are safe, secure and validated – but it’s not impossible. “To us,” Sacks says, “best practice would be having well-validated systems and making sure that the technology has been verified. When different technologies are used, performance specifications may be important to ensure that they can be used interchangeably.
“We have a lot of safeguards in there to make sure that things are ethical and that they’re scientifically reliable,” Sacks continues. And it’s not just the FDA that holds this view. As Shaw explains, “[there has been] a big global push for interoperability; in other words, having the same data structured the same way so that it can be exchanged. The major group doing this is called Health Level 7 (HL7), which is an international organisation that’s been pushing for years, and they’re really creating these centralised data exchanges that are global.”
These frameworks and systems have been in place for some time now, but we’re still on a learning curve. “We’re not in the early days,” Shaw muses, “but we’re in the young days of trying to match up how the technologies have promise, but what’s the reality of how they’re going to be used?” As Sacks notes, “The big difficulty is that we don’t yet have the experience. We don’t have a thorough knowledge of how participants in trials are going to use them, how effectively they’re going to work for them. There are concerns that elderly patients may not be able to use these technologies comfortably – they may be less computer savvy.
“Others may have physical difficulties, for example, patients with Parkinson’s may not be able to press small buttons. So, we have to learn about how patients will use them, how reliable they’ll be, and whether they’ll keep using them during the duration of the trial.” In a sense, then, DCTs are a kind of double trial, testing not only a drug, but a digital toolkit, too. “That’s probably where we are at the moment,” Sacks agrees. “These advanced technologies have not been used to any significant extent as the sole measurement in a clinical trial. But I think they’ll develop independence as we become more confident with them and as industry becomes confident with them.”
A bright future ahead
For Zibert, Sacks and Shaw, the future of DHTs looks bright. In the next ten years, they all agree that these technologies will be widespread, not only in clinical trials, but across healthcare – but only if developers design with the patient in mind. “I think the main thing that a lot of people are doing wrong is that they make an app and then they release the app, and then they think that all is good now. That’s not the case,” Zibert stresses. “The overarching goal of Studies&Me is personalising treatment development and that is exacted by listening to the voices of the patients, and also the doctors, to ensure that they understand, they feel motivated, and that they also gain something out of the clinical trials. You cannot just make one app that fits all – you have to make an app that fits the target population of your trial.” It’s a refrain that all three echo.
So, what does a patient-centric clinical trial look like, in an ideal world? “Patient-centric,” Zibert says “is if you want to do your trial visit with the doctor when you’re at the sea. Or in a forest. You can do it where it suits you the best, where you feel that you are in the scope of being yourself.” Welcome to the world of remote health – the toolkit to the future is already in your hands.
