By Lucy Fulford on Apr 3, 2020 / https://www.reutersevents.com/

The restrictions on movement and normal interaction owing to COVID-19 pose a distinct challenge to the traditional clinical trial model, as patients, investigators and clinical staff are either confined to their homes or seeking to avoid healthcare settings.  Those running clinical trials over the past weeks have had to adapt rapidly by fast-tracking digital capabilities to ensure continued delivery. With the future of existing trials hanging in the balance, some have been pivoting to remote delivery – sometimes in the space of under a week.  Speaking at eyeforpharma Virtual, a digital version of the Barcelona event which can be accessed for free online at https://virtual.eyeforpharma.com, experts in virtual trial delivery discuss the implications and opportunities for organisational reform, telemedicine, and new trial models that will arise from the crisis.  

“The world has changed radically over the past couple of months to weeks,” says Michelle Longmire, CEO of digital trial platform Medable, which has been working with pharma and biotech companies, CROs and academic research centres to shift standard clinical trial methodologies to telemedicine.   “The first challenge we were faced with was clinical trials in-flight, where patients were coming in for face-to-face visits and suddenly – specifically in Italy – you had a number of sites which were no longer available for physical visits. Over the last couple of weeks, we’ve taken major strides to facilitate decentralized clinical trials.”  Medable has been deploying direct-to-patient technologies to deliver remote clinical trials within a week. “This was enabled through a mobile application that we made globally available,” says Longmire of one deployment, relying on patients’ existing smartphones. “The consent form in the native language consents the patient for the addition of telemedicine. In this case it did not require a protocol amendment – the primary purpose was to ensure that the endpoint data could be collected and to evaluate the patient’s well-being and overall safety status. “If participants are in critical windows, we should leverage telemedicine to continue that endpoint data capture where appropriate, so that we don’t lose that participant’s contribution.” 

Such rapid changes are being made possible thanks to a responsive regulatory framework. Both the FDA and the EMA have been sending out new guidelines, says Rasmus Hogreffe, Head of Virtual Clinical Trials at LEO Innovation Lab, to enable trial participants to remain in studies.  

“The authorities around the world, the regulators and the ethics committees have worked very fast to release guidance with a common theme – to protect patient safety and reduce the hazard to patient and clinician lives,” says Alison Holland, Head of Decentralized Clinical Trials at Medable.  When establishing a virtual clinical trial under these circumstances, the same standards in patient safety and data control apply, says Holland, including carrying out comprehensive risk assessments, establishing what the primary data is and the safety around either continuing or halting treatments.  “It takes an army to be able to be nimble and to adapt to these change in needs and make sure that we’re not leaving out any important considerations as we deploy these studies,” she says. “That risk assessment is really critical and then converting that into a deployment project plan around how to bring all the different parties together.” Regulatory, ethics and project management teams at CROs need to work alongside site staff, and now software teams as well, to ensure seamless digital delivery and a full appreciation of data privacy and security, amid the ongoing management of clinical delivery and physician-patient relationships.  Decisions also need to be made about device usage. While Medable has been able to deliver devices to participants and clinicians even in hard-hit areas such as Italy, being able to use phones rather than body sensors and other devices is preferable for hygiene and safety.  “Every protocol is different and there’s not a one-size-fits-all approach, but it’s about applying configurable technology, assembling the right set of services to support the patient and site, and then engaging the site and clinical staff with the tools to empower them to apply their skills to that clinical trial,” says Longmire. “Fundamentally, it’s about tools, partnership and collaboration.” 

 A path to better outcomes: While telemedicine may initially be a stop-gap in today’s altered landscape, it could also lead to a broader transition from site-based models to a full decentralisation of future studies.  “Before COVID-19, we were looking at the benefits of to be participant diversity and broader access were seen as the chief benefits of decentralised trials, prior to the current crisis but now other possible advantages are emerging, says Longmire. “It could lead to other benefits, such as reductions in time due to faster and better enrolment, or an increase in patient retention due to more convenient trials, which can also reduce clinical trial timelines.”   

Far from being framed as a make-do or next-best, the virtual clinical trial adds value, says Hogreffe, offering distinct advantages in terms of data quality, cost-saving and retention. Hogreffe cites the 13-plus remote studies run by LEO Innovation Lab. In its genoME study on atopic dermatitis, for example, 55 participants enrolled from across Denmark over seven days, with a retention rate of more than 96%. The potential is vast given the explosion of global smartphone usage, which places an invaluable resource in almost every would-be patient’s hands. “We believe that next year we will have access to more than 6.3 billion smartphones,” says Hogreffe.  Connected medical devices mean clinicians can evaluate patient wellbeing and conduct outcome assessments, as well as capturing important physiological data, such as sleep measurements, respiratory rate, heart rate, temperature and EKG. Conditions which are defined subjectively through symptomatology and behaviour lend themselves to such assessment, says Mads Dalsgaard, Senior Vice President, Head of Experimental Medicine & Clinical Development, Lundbeck. “Especially within brain diseases, remote assessment can really be a means for improving outcome measures,” he says. 

Embedding change for the future: There is a pressing need to act on these digital advancements, adds Dalsgaard, as clinical development is still characterized by long development cycles, high failure rates and high costs.  “We haven’t really seen the rise of technology translate into expedited clinical development cycles,” he says. “It’s somewhat surprising, because if you look at the whole ecosystem, there is a really strong foundation in place. There’s no doubt that virtual trials are a very important solution to cracking these challenges.”   There will always be a need for some trials to have a physical presence, he says, from taking blood samples to certain necessary safety measures, so he favors an “80/20 rule”, rather than trying to aim for 100% remote assessment. But some conditions, such as dermatology, are ideal for remote monitoring – LEO’s apps allow patients to photograph skin conditions, with machine learning able to detect whether the picture is in focus, optimally-lit and therefore suitable for submission.  The advances that happen in executing clinical trials through greater digitization should also hopefully be the catalyst for further improvements in the way pharma tries to innovate throughout the clinical sphere too, says Dalsgaard.  “Virtual execution of clinical trials is an essential way of improving the way we do clinical development, but there’s also a lot of value to be derived from looking at other parts of the clinical development value chain. Digitalization should focus equally around business processes. “I really believe that the COVID-19 outbreak will drastically change the way that we run clinical studies in the future,” adds Hogreffe. “We simply cannot ignore the advantages of involving these technologies – we can have a much safer, much more cost-efficient trial design in the future.”