While decentralized trials existed before COVID-19 arrived, the pandemic greatly increased acceptance and adoption of the study format. Ivan Jarry, CEO of ObvioHealth, spoke with Outsourcing-Pharma about how DCTs have offered lessons that could help industry professionals improve operations as they increase their decentralized activity.
OSP: Could you please talk a bit about the evolution of decentralized and hybrid clinical trials, before COVID?
IJ: Before COVID-19, decentralized clinical trials (DCTs) and hybrid trials were almost nonexistent. The technology existed—but nobody was using it, because big pharma was hesitant to take risks. There were a few innovative companies that began experimenting with DCT trial components, but overall, these models weren’t taking off.
ObvioHealth had been running clinical studies for 15+ years out of SPRIM, our parent company. We realized in 2016 that there must be ways to digitize part of the traditional clinical trial process to be more efficient.
For example, we realized that it was inefficient to send participants to a site to do basic questionnaires and basic measurements when they could do this on their own time, at home. This is when we came up with the idea of a mobile app that would make participation in studies a lot easier for the patients. We associated the app with a platform that was modular, so that sponsors could either run fully decentralized trials or just choose a module, like eConsent or ePRO.
We also realized that technology was not the only solution—that the human factor was extremely important. We had to find a way to replace what a site team did—scheduling, monitoring, and communicating with patients. So, as part of our solution, we integrated a virtual site team that is available to engage with, and support, patients throughout the trial.
And, because our company was originally set up in Singapore, our first studies were actually run in Asia. From the beginning, we built a platform that was cloud-native that we could deploy in different countries with different regulations around the usage and transfer of data.
OSP: How has the DCT realm, and the way sites/sponsors approach such trials, changed in recent months, with the industry continuing to adapt to COVID?
IJ: There were two periods of adaptation: the first was when COVID hit and sites started closing and DCTs were the only options for many studies to continue.
Luckily, after several months, sites started to reopen. This is the second period, during which sponsors had the choice of running trials in the traditional model (site-based) or continuing with decentralization. Sponsors chose the latter because they saw the benefits to all involved: the sponsor themselves get results more efficiently, patients are less burdened, and even the traditional sites are able to lighten their load by digitizing some of their processes.
As a result, the adoption of DCTs has happened quite quickly over the past year, with more than three-quarters of sponsors expecting to run their own DCTs over the next 12 months. Sponsors are looking to reduce the number of site visits where it makes sense. Non-essential visits are being replaced by remote patient monitoring or telehealth visits.
OSP: Can you share your thoughts on some of the mistakes, lessons learned, areas for improvement?
IJ: One of the most important lessons learned is that technology alone is not enough. We’ve seen that adherence to protocols and participant compliance increases significantly when there is support from a virtual or hybrid team. The combination of technology and humans is essential.
We’ve also recognized the need to give patients choices. Different people will have different preferences, and studies need to be designed to provide options. Some people don’t want to be visited at home. So, the model of replacing a physician visit on-site with an at-home visit by a nurse is not always the right solution.
One misperception on the part of some sponsors was that DCTs would always be more cost-effective. But, in cases where the virtual study is overlaid on top of a multi-site study, the costs can sometimes go up rather than down, because sponsors have to pay the CRO fees plus the sites, as well as the software platforms that enable DCTs. The most significant cost savings are obviously when it is possible to eliminate the need for a CRO and/or for traditional sites and run the full study virtually.
Finally, we have learned a lot about the need to do everything to help patients remain compliant and engaged. When you run a decentralized model, you are shifting the burden of collecting outcomes from the physician and nurses at the sites to the patients at their homes via apps and devices. This means that patients need to be informed and trained because they’re playing a more active role in the trial.
Here too, UX becomes extremely important. The tasks and the technology need to be simple and intuitive to encourage compliance and ensure you are capturing the correct assessments.
OSP: As you point out, there is an increased need/demand for digital instruments. Could you share your thoughts on how instrument technology needs have changed thanks to the expansion of virtual trials?
IJ: Originally, digital instruments were associated with consumer-grade wearables that we could use to track different activities. Next, there was an evolution towards medical-grade, FDA-approved devices, which are more precise in their measurements. But, they are also a lot more cumbersome and complex for the patient to set up and manage.
Often, they are also not good at accurately measuring more than one outcome, which sometimes leads to the need for patients to use several devices and risks overburdening them.
But, there are also other innovations in digital instruments related to the technology that we all have in our pockets: our phones. Increasingly, these instruments have a quality of sound and image capture that is superior to many of the instruments that hospitals currently provide or that can be obtained through eClinRo.
For example—and this is based on one of the studies we’ve done—if you ask a parent via questionnaire, “How long has your baby been crying?” they might tell you 15 minutes—you’re dealing with the participant’s subjectivity. But, if we use our mobile app to detect and record the baby’s cry, we discover that the baby was actually crying for five minutes.
In situations like these, simple digital instruments built for passive data collection (of course, with the proper consent and guardrails) on mobile phones can give us more accurate information than patient-reported outcomes in a way that is also less burdensome.
The final point is that you always need to start with the endpoints and work backward in order to identify the right instruments to achieve those endpoints. Not enough thought is being given to the absolute relevance of the technology in order to deliver the necessary endpoints.
The industry has been using a very antiquated library of instruments to measure certain endpoints; these instruments were validated 20, 30, 50 years ago. And, now we have the technology and the intelligence to create and redefine the instruments that are the most adapted, the least invasive, and the most accurate.
OSP: As the increased need for digital DCT tools is met, what are some of the ways in which trial teams must adapt? Feel free to talk about any or all stages of the journey--study design, patient monitoring, data collection/management, etc.
IJ: Recruitment is of huge importance when considering this question. Traditionally, a site would desperately try to find patients that fit the inclusion and exclusion criteria for a specific trial within their limited database. They would advertise on the radio, in newspapers, and have pamphlets around the site to attract participants.
Online recruitment for decentralized trials removes this geographic constraint: you have a broader pool to recruit from, enabling the team to recruit a cohort that may be more representative of the target population, resulting in a more diverse sample.
We’ve had to redefine the role of every single person in our organization. For example, the clinical coordinator who previously managed patients from sites now has the technology to assist them with the mundane tasks so that they can focus on the patients who need assistance with, for example, eConsent.
A participant can preschedule video or phone calls with a coordinator who will review the consent documentation with them. The technology can monitor scrolling speed and integrate quizzes to ensure participant understanding. Coordinators can also be alerted when there appears to be an issue of understanding and can easily schedule follow-ups.
Like clinical coordinators, data manager roles are also evolving. They are no longer just looking at tables of data and trying to identify inaccuracies. They now program the system to perform automatic edit checks, identify patterns, structure ensuing tasks and then treat them.
Across the board, these roles have become less repetitive and more focused on strategic interventions—either assisting patients or addressing data abnormalities.
OSP: How can ObvioHealth help clients assess their instrument situation and ensure they’re using the best digital tech for the job?
IJ: ObvioHealth’s clinical science team can help clients by interrogating their protocols to fully understand the desired endpoints and optimize around them. This involves the identification of the most efficient, safe, and valid tools in order to improve the reliability, real-time nature, and accuracy of outcomes.
The best instrument is not necessarily the most complicated one. Using a keep-it-simple approach, we are able to leverage training, design simplicity, and technology to facilitate the most accurate outcomes.
ObvioHealth is also pioneering new digital instruments to achieve better outcomes (e.g: instruments that will go beyond reporting an event to also capture its frequency and severity). To date, our clinical science team has successfully delivered over 250 novel instruments, across therapeutic areas and indications, to meet client needs. These new digital instruments are already contributing to the identification of novel outcomes for coughing, stools, and infant crying. The addition of vitals data captured from validated devices (eg: 6-lead EKGs and blood oxygenation captured via remote monitoring medical devices) is also contributing to better safety monitoring.