Is COVID the gamechanger for decentralized trials?
There is a golden opportunity to deliver clinical trial innovation post-pandemic given healthcare’s appetite for new approaches, such as virtual patient consults and more efficient trial designs
The shortcomings of the current model for clinical research are well documented. It costs around $26,000 to enroll the average trial participant, of whom one in three typically drops out during the study. This leads to significant delays as only one in seven trials succeeds in enrolling patients in sufficient numbers.
More worryingly, 18% fail to attract a single patient. The consequences are dire, not just in terms of the $40bn that the pharma industry wastes merely on ‘time costs’ every year. Many patients never learn of clinical research as a viable treatment option, and if they do, their participation remains fraught with obstacles.
“Structural and clinical barriers are the reasons more than three out of four patients do not participate in trials” says Dr. Joseph Unger, a health services researcher at the Hutchinson Cancer Research Center, and author of a recent systematic review published in the Journal of the National Cancer Institute.
Since 70% of US target patients live more than two hours from the closest authorized research site, many industry stakeholders have come to believe that changes such as remote participation and research de-centralization are the only viable answers to fixing the current system.
COVID 19 as an inflection point
More than a decade since the first decentralized clinical trial was run, progress in scaling remote data collection and distributing clinical research activities has lagged far behind the technological innovation ready to enable it.
But the advent of the widespread pandemic restrictions looks like it is changing all this: While the initial impact was negative – according to data published in The Lancet, 80% of non-COVID trials were either interrupted or stopped – there is now a surge in calls to accelerate the use of home health coordination and other remote monitoring technologies such as eCOA, eConsent, ePRO or wearables.
“COVID has absolutely been a catalyst to dramatic changes,” says Jennifer Goldsack, Executive Director at the Digital Medicine Society. “We are now moving towards a situation where we are building clinical trials for the first time around the patient, instead of the clinic and the industry and we have a suite of resources to do that, that we have never had before.”
As often with pharma operations, progress has happened in incremental steps. As the pandemic unfolded, traditional in-person visits required in the research protocol were completed remotely, following the broad easing of restrictions for telemedicine. “We're now seeing an increase in using these functional modalities in different visits,” says Jeremy Price, Director, Clinical Innovation & Strategic Partnerships at Pfizer.
Looking at a one-year protocol with monthly visits, for example, sponsors now evaluate the feasibility of substitution with home-based or local check-ins, says Price. “Can we do one or two of those visits remotely? Can they be done from home? Could you go get blood drawn in your local area instead of driving two or four hours to a site?”
Such questions are now routinely brought into protocol design for studies at Pfizer. The novel innovation mandate is to “bring research to the patient as opposed to bringing the patient to the study”, says Price.
Patient-centered technology as the key enabler
“Perhaps one of the few silver linings of the pandemic is that digital transformation is accelerated as to the way to start the trial and engagement with the patient, even during the prescreening process, videos and online tools,” says Joe Dustin, Head of Clinical Innovation and Change Management at Bristol Myers Squibb.
Regulatory willingness to see patients verified and onboarded via virtual visits is changing too in many countries.
There is a great opportunity to use technology to create a better patient experience as well, says Rob DiCicco, Deputy Chief Health Officer at IBM Watson Health. The proper use of feedback, for example, can help identify aspects of a disease that were previously unsatisfyingly captured via traditional outcomes measures.
“To listen to patients about what they want us to measure in a clinical trial that would make it compelling for them to participate, requires us to be very, very thoughtful about how we now start to develop digital and other nontraditional endpoints,” says DiCicco.
From tailored approaches to a universal platform
In driving changes towards wider adoption of decentralized trials from the sponsor perspective, BMS’s Dustin notes that technology tools and services need to be mutually enhancing.
This requires a close understanding of the realities out in the field including the practicalities of direct drug supply to homes, of remote monitoring and also of the role of Contract Research Associates (CRAs) who enable study success through various personal engagement activities. “It’s not just putting a mobile app in the patient's hand and have them going home, that’s not it.” says Dustin.
The future model for decentralized trials will also require a degree of automation and standardization, moving away from bespoke and episodic deployment towards the adoption of a multi-stakeholder platform.
“I think sometimes when we get into the weeds talking about new methodologies or new technologies today, we get very, very close to the ground and look through one individual's lens only,” says DiCicco. “We’re talking about disrupting an ecosystem that has a lot of different important stakeholders, but most importantly one with the patient at the core.”
When it comes to building that holistic approach, “integration must occur at the large core system and at the device level such as wearables or mobile,” says DiCicco. Many tools could readily be templated, however, he adds. “Even in the routine brick and mortar approach to conducting clinical trials, there are a lot of things that we do not reuse, whether it's ePRO, informed consents, or EDC libraries.”
Between a fully remote trial, a decentralized trial and a hybrid study, there are many ways to virtualize core capabilities. Experts agree that empowering patients and better activating them in their local care circle via changes in study design and planning is overdue. Giving patients choices will become the new normal, says Dustin. “There's no going back on this, if you think about the post-pandemic blueprint.”
But the transition requires a complete rethink by all stakeholders. “To truly use the activation energy that we receive from the COVID transformation, we need not limit ourselves by just trying to copy and paste what we've always done into different places,” says the Digital Medicine Society’s Goldsack. “We really need to think about the whole process differently.”
Digital equity, new approaches to IP, broader access to care and proper socio-economic representation are important considerations in this new multi-stakeholder dialogue. In December 2020, leaders representing more than 50 organizations formed the Decentralized Trials & Research Alliance (DTRA) to tackle these challenges. The unprecedented initiative has yet to share any specifics, but its mission is to “make research participation accessible to everyone”.
To keep up with the current pace of biomedical and pharmaceutical innovation, it is estimated that up to 40 million future patients are required to join clinical research every year. This is only about a tenth of one percent of the patients who actually participate across all studies for FDA-approved products annually. It is fair to say that the moment to supercharge a collective transformation for a more inclusive clinical trial enterprise is overdue.