COVID-19: The Great Decentralized Clinical Trials Accelerator

here’s no better way to truly understand the patient experience than to become a patient in the midst of an unprecedented global pandemic. I found myself in this position in early March, when I was transported to the hospital by ambulance late one night after experiencing increasingly severe symptoms of COVID-19. Though much of it is a blur, it was clear the next morning when I awoke that many of the nurses were working on the COVID-19 unit for the first time. They spoke of concerns about transmitting the disease to their children at home, confusion over continually changing instructions for proper PPE use, and questions about whether they should be working at all.

Surrounded by elderly and frail patients who looked equally as frightened as I was, it was clear that a hospital was the last place we wanted to be, and the prospect of home-based care was a very appealing option. Although I had always embraced decentralized clinical trials (DCTs) as a way to reduce the patient burden and sought to incorporate them into trial designs, I realized it was now imperative that our industry employ this model as a means of ensuring patient safety and enabling ongoing trial participation during the pandemic.

For those unfamiliar with DCTs, these are the key elements and their implications for patients:

• Patient Apps: Enable participants to eConsent, complete ePRO measures and surveys, receive visit reminders and motivational messages, and participate in telehealth (video) calls with site staff. This means that in-person appointments can be replaced but patients stay connected and engaged in the study, their safety can effectively be monitored by the investigator, and data quality is still maintained.
• Direct-to-Patient Drug Shipments: Ensure that study medication is provided to patients in their home even when they cannot, or do not want to, visit the site. Patients therefore can remain compliant with their treatment schedule while staying safe and participating in a way that meets their needs.
• Sensors: Support remote data collection directly from the patient (e.g., wearables like actigraphs that monitor activity levels) or their environment (e.g., air quality). This can replace some traditional methods and reduce the number of physical appointments.
• Home Healthcare: Simple tests and procedures, such as blood draws and recordings of vital signs, can be performed in the home by visiting nurses, allowing patients to complete some or all visits successfully without travelling to the study site.

There is rising consensus that DCTs have become increasingly important in recent months. After years of hesitation to employ this approach, the industry is now embracing home-based trials to ensure continued patient oversight and collection of quality data during the pandemic. Companies are adapting trials from site-based to fully decentralized or hybrid models, and over half of new trials we’re seeing are incorporating decentralized elements from the start, both to accommodate patient preferences and to prepare for a second wave of COVID-19. They are now viewed as essential tools rather than nice-to-haves.

For sites, this change can mean adopting, and adapting to, new technology that was previously viewed by some as unnecessary or too time-consuming to learn and employ. Innovation and ingenuity blossom during challenging times, and utilizing DCT techniques has become a critical part of patient care and safety monitoring. One investigator recently commented that she had previously been reluctant to conduct video visits. But, after trying it, she realized she could still establish very real, human connections with her patients and would happily continue this approach post-pandemic. Such rapid adoption of telemedicine—borne out of necessity—will aid in longer-term adoption thanks to increased confidence. Moreover, telemedicine serves more than a medical purpose by reducing social isolation for patients who have needed to stay home — an added mental health benefit.

Tactical issues, such as shipping study drugs, have also required rapid adaptation during the pandemic. Instead of shipping drugs to the sites, direct-to-patient shipments during lockdown have enabled continuity of drug supply to study participants who are unwilling or unable to attend their scheduled trial visits due to COVID-19. Using specialist couriers, this solution has been swiftly and effectively deployed in many countries across the globe, with careful oversight and management to ensure that the drug arrives on time and in optimal condition. Patients are highly amenable to receiving medications directly at their door, as many individuals have been relying heavily on deliveries of all kinds of items since social isolation measures began.

Conversely, uptake of sensor technology during the COVID-19 pandemic has occurred at a much lower volume. Biopharma companies have recognized the impracticality of taking time for validation studies to ensure that the device is effective in a real-world setting prior to use in a study at a time when solutions require swift implementation. In addition, there is still variability in regulators’ perceptions of sensor data, so a tentative approach to this solution is understandable. For sites involved in adding sensors to existing studies, training is needed so they feel comfortable enough with the technology to explain the details to their study participants. As for patients, using sensors is a challenge for some whereas others easily adopt it, depending largely on their level familiarity and comfort with technology. Telehealth instruction and home nurse guidance are both used to support sensor use and adoption to enhance patient compliance.

Home nursing has also seen greater adoption during the pandemic. However, this is usually undertaken via a central vendor, which can be a sensitive topic with sites that prefer that their own nurses conduct patient visits. However, centralizing all processes, insurance, scheduling, and documentation can streamline trials considerably. Providing own nurses to conduct patient visits has been relaxed to some degree and, in select areas, out of necessity during the pandemic to ensure that patient safety is closely managed. As with direct-to-patient drug shipments, careful resource planning has been required to support provision of home nurses to access patients in greatest need. In some regions, these nurses have been pulled into local hospitals to help manage the volume of admitted patients, some have been patients themselves and others may have chosen not to work in order to protect their families. One aspect that has remained largely constant is the standard process of engagement with sites, where the principal investigator is still able to review and approve the curriculum vitae of the proposed nurse allocated to their patients, undertake a video (rather than in-person) meeting, continue liaising during the trial to ensure patient safety, and review visit details as required.

There has been variability in how patients have responded to the offer of receiving home nurses. Some have preferred to continue with site visits where possible; others have appreciated the ability to be seen at home. Although the duration and severity of lockdown restrictions has varied across countries, most patients have required an average of eight to 12 weeks of support before they are able to visit their site again to continue with their trial as normal. It is important to give patients the choice to be treated where they feel most comfortable as they all strive to navigate the unknowns while already managing an existing health condition.

Although nobody can predict the future of post-COVID-19 clinical research, the shift toward greater adoption of DCTs is likely to continue. Many regulators were quick to adapt guidance to accommodate DCT services. It is hoped that this approach continues once they see the evidence of benefit to patients, such as improved access to research and a more positive trial experience. With improved recruitment and retention afforded by DCTs, economic pressure may also push industry toward deploying a higher volume of DCTs to advance drugs to market faster. Sites have also acquired DCT experience that increases their comfort level and demystifies decentralized services, and patients may well request to participate in trials from home, now that they know it is possible.

With greater convenience for patients and reduced geographical, financial, and practical barriers to participation, the pandemic has pushed the industry toward swift adoption of DCTs. The global health crisis has been a learning experience for patients and sites in ways that nobody could have anticipated. Still, with new forms of communication thrust upon them, people have adapted and thrived. With all that has been learned, it is likely that DCTs will be here to stay long after this terrible virus has been tamed.