Deployment of an End-to-End Remote, Digitalized Clinical Study Protocol in COVID-19: Process Evaluation

Abstract

Background The SARS-CoV-2 (COVID-19) pandemic may accelerate the adoption of digital, decentralized clinical trials. Conceptual recommendations for digitalized and remote clinical studies and technology are available to enable digitalization. Fully remote studies may break down some of the participation barriers in traditional trials. However, they add logistical complexity and offer fewer opportunities to intervene following a technical failure or adverse event. Objective Our group designed an end-to-end digitalized clinical study protocol, using the Food and Drug Administration (FDA)–cleared Current Health (CH) remote monitoring platform to collect symptoms and continuous physiological data of individuals recently infected with COVID-19 in the community. The purpose of this work is to provide a detailed example of an end-to-end digitalized protocol implementation based on conceptual recommendations by describing the study setup in detail, evaluating its performance, and identifying points of success and failure. Methods Primary recruitment was via social media and word of mouth. Informed consent was obtained during a virtual appointment, and the CH-monitoring kit was shipped directly to the participants. The wearable continuously recorded pulse rate (PR), respiratory rate (RR), oxygen saturation (SpO2), skin temperature, and step count, while a tablet administered symptom surveys. Data were transmitted in real time to the CH cloud-based platform and displayed in the web-based dashboard, with alerts to the study team if the wearable was not charged or worn. The study duration was up to 30 days. The time to recruit, screen, consent, set up equipment, and collect data was quantified, and advertising engagement was tracked with a web analytics service. Results Of 13 different study advertisements, 5 (38.5%) were live on social media at any one time. In total, 38 eligibility forms were completed, and 19 (50%) respondents met the eligibility criteria. Of these, 9 (47.4%) were contactable and 8 (88.9%) provided informed consent. Deployment times ranged from 22 to 110 hours, and participants set up the equipment and started transmitting vital signs within 7.6 (IQR 6.3-10) hours of delivery. The mean wearable adherence was 70% (SD 19%), and the mean daily survey adherence was 88% (SD 21%) for the 8 participants. Vital signs were in normal ranges during study participation, and symptoms decreased over time. Conclusions Evaluation of clinical study implementation is important to capture what works and what might need to be modified. A well-calibrated approach to online advertising and enrollment can remove barriers to recruitment and lower costs but remains the most challenging part of research. Equipment was effectively and promptly shipped to participants and removed the risk of illness transmission associated with in-person encounters during a pandemic. Wearable technology incorporating continuous, clinical-grade monitoring offered an unprecedented level of detail and ecological validity. However, study planning, relationship building, and troubleshooting are more complex in the remote setting. The relevance of a study to potential participants remains key to its success.

Narrative review of telemedicine applications in decentralized research

“…Infrastructure and training are essential in decentralized research [ 23 ]. Researchers must closely consider privacy and confidentiality when selecting and configuring telemedicine technologies.…”

“…A telemedicine process and workflow must be designed to support participant interactions with the research team, including essential logistics such as scheduling and staffing, communication with participants, arrangement of physical space, and hardware management. The telemedicine process must also include in-call processes that support protocol integrity and participant engagement, configuration and implementation of adjunct telemedicine technologies such as teleconsent and messaging, and mechanisms for technical support [ 23 , 24 ]. Additionally, telemedicine technologies are secure communication modalities for investigative teams, stakeholders, and collaborators to discuss and manage study protocols, recruitment successes and challenges, and support efficient conduct of the study [ 25 , 26 ].…”

“…Scheduled or acute telemedicine consultations can help participants to report adverse events during the trial period and receive immediate medical care [ 24 , 95 ]. Furthermore, digital cloud-based platforms could empower researchers and clinicians by sending real-time alerts and notifications about potential concerns based on participants’ self-reported symptoms or medical device data [ 23 ].…”

Methods and perceptions of success for patient recruitment in decentralized clinical studies

“…All aspects of clinical research were disrupted by the onset of the COVID-19 pandemic, suspending ongoing trials, delaying the start of new studies, and hindering participant enrollment [9]. The technology for successful incorporation of digital methods into clinical studies has existed for over 20 years, and although decentralized methods have been used in prior clinical studies, the circumstances brought about by the COVID-19 pandemic created conditions for which their adoption became necessary [10]. In order to mitigate the risks of COVID-19 while resuming research activity, the FDA as well as the National Cancer Institute issued guidance providing flexibility to clinical investigators for the adoption of decentralized methods in conducting clinical trials [11,12].…”