Two recent papers detail the pathways and learnings from a fully virtual, direct-to-patient trial and from a traditional trial that adapted to virtual practices during the COVID-19 pandemic.
Research conducted remotely presents a number of benefits to clinical research—along with unique challenges. Two ongoing studies at the DCRI recently detailed these pros and cons in recently published design papers.
The studies were designed with different goals in mind. PUSH, a urology study, initially employed a fairly traditional design, with in-person enrollment at the clinic. However, the intervention that PUSH was testing was novel. In an effort to empower people to reduce risk of recurrent kidney stones with better hydration, researchers wanted to determine whether use of a “smart” water bottle and an app to track hydration, paired with a program of financial incentives and health coaching, would result in reduced risk of kidney stones.
iPERSONAL, on the other hand, employs a completely novel design as DCRI’s pilot “direct-to-family” study. By bringing research to participants’ homes rather than relying solely on in-person clinic visits, direct-to-family research presents opportunities to alleviate the burden of research for both participants and sites alike. The aims of iPERSONAL are two-fold: one, to see if a digital pill bottle cap improves adherence to medication for patients with pediatric lupus, and two, to determine the most accurate dose of hydroxychloroquine, a commonly used lupus drug, for these patients.
While iPERSONAL was designed from the outset to be conducted completely virtually, PUSH was not. When the COVID-19 pandemic made in-person clinic visits no longer feasible, the PUSH study team had to quickly adapt, shifting to completely remote recruitment and enrollment.
DCRI urologist Chuck Scales, MD, principal investigator for the PUSH study, recently co-authored a paper along with his co-investigators about learnings from continuing to conduct the study during the pandemic. The paper was published in The Journal of Urology.
“The cornerstone is the remote consent process, which has practical and scientific advantages,” the authors wrote. “Practically, remote consenting allows greater flexibility in scheduling, eliminates the need for clinic research space, increases enrollment speed, and opens up trial participation to individuals living in rural areas or at distance from a site.” For PUSH specifically, remote enrollment allowed the team to expand recruitment nationwide.
The study team behind iPERSONAL, led by DCRI adult and pediatric rheumatologist Stephen Balevic, MD, also recently published a paper in Lupus Science & Medicine which detailed the design and implementation of the direct-to-family trial. The authors underscored the predicament that the study team behind PUSH and so many other studies faced, writing, “At least 1,600 clinical trials have been terminated, suspended or withdrawn due to COVID-19, making teleresearch an urgent, unmet need.”
Research has shown that direct-to-family studies “can improve participant recruitment and retention, increase participant diversity, improve efficiency and reduce costs,” the authors wrote. The iPERSONAL study exemplified improved and expedited recruitment, completing enrollment via e-consent in just 10 days.
Despite benefits like these, virtual trials are also accompanied by challenges. The iPERSONAL paper described several considerations: the importance of choosing outcome measures that can be assessed remotely, the need to have a monitoring plan that will keep patients safe during a remote study, and the difficulty of verifying whether a patient is diagnosed with the disease being studied without a clinic to verify diagnosis.
Investigators from both studies overcame the last challenge by relying on partnerships. The iPERSONAL partnered with the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, which helped them to verify that interested patients had a confirmed diagnosis of pediatric lupus, and the PUSH investigators worked with expansive health systems within the USDRN to identify patients who received care and were eligible for the trial.
While the pandemic required mid-study adaptations for many studies like the PUSH study, other studies like iPERSONAL prove that such innovations can also be implemented at the initial design stages of a study to make research easier for participants and to result in more generalizable findings. As the PUSH investigators wrote in their paper, “It is important to acknowledge that these adaptations can be adopted even without a pandemic, and thus have theoretical and practical implications for conducting future (randomized controlled trials).”