The future is now: our experience starting a remote clinical trial during the beginning of the COVID-19 pandemic

Abstract

Background The World Health Organization declared the outbreak of SARS-CoV-2 a pandemic on February 11, 2020. This organism causes COVID-19 disease and the rapid rise in cases and geographic spread strained healthcare systems. Clinical research trials were hindered by infection control measures discouraging physical contact and diversion of resources to meet emergent requirements. The need for effective treatment and prevention of COVID-19 prompted an untested investigational response. Trial groups adapted approaches using remote enrolment and consenting, newly developed diagnostic tests, delivery of study medications and devices to participants’ homes, and remote monitoring to ensure investigator/enrollee safety while preserving ethical integrity, confidentiality, and data accuracy. Methods Clinical researchers at our community health system in the USA undertook an outpatient randomized open-label study of hydroxychloroquine (HCQ) prophylaxis versus observation of SARS-CoV-2 infection in household COVID-19 contacts. Designed in March 2020, challenges included COVID-19 infection in the research group, HCQ shortage, and lack of well-established home SARS-CoV-2 tests and remote ECG monitoring protocols in populations naive to these procedures. The study was written, funded, and received ethical committee approval in 4 months and was completed by September 2020 during a period of fluctuating infection rates and conflicting political opinions on HCQ use; results have been published. Singular methodology included the use of a new RNA PCR saliva SARS-CoV-2 home diagnostic test and a remote smartphone-based 6-lead ECG recording system. Results Of 483 households contacted regarding trial participation, 209 (43.3%) did not respond to telephone calls/e-mails and 90 (18.6%) declined; others were not eligible by inclusion or exclusion criteria. Ultimately, 54 individuals were enrolled and 42 completed the study. Numbers were too small to determine the efficacy of HCQ prophylaxis. No serious treatment-related adverse events were encountered. Conclusions Flexibility in design, a multidisciplinary research team, prompt cooperation among research, funding, ethics review groups, and finding innovative study approaches enabled this work. Concerns were balancing study recruitment against unduly influencing individuals anxious for protection from the pandemic and exclusion of groups based on lack of Internet access and technology. An issue to address going forward is establishing research cooperation across community health systems before emergencies develop. Trial registration ClinicalTrials.govNCT04652648. Registered on December 3, 2020.

Implementing an outpatient clinical trial on COVID-19 treatment in an emergency epidemic context: a mixed methods study among operational and research stakeholders within the Coverage trial, Bordeaux (France)

“…The set-up and early implementation of the Coverage trial in the COVID-19 outbreak context involved and/or requisitioned the involvement of a large number of actors from several disciplines, which was perceived as a source of dynamism by interviewees; this has been reported in another study in the USA [ 34 ]. However, while the motivations of young clinicians and GPs to be involved in clinical research, to train on-the-job, and to participate in the Coverage trial implementation was praised by some of the stakeholders interviewed, others questioned whether this lack of prior training and experience has been an obstacle to the implementation of the trial.…”

Participant and research team perspectives on the conduct of a remote therapeutic COVID-19 clinical trial: A mixed methods approach

“…Yet another could be use of asynchronous technology using images or data collected at one point in time and responded to later [34]. Further exploration of electronic patient-reported outcomes and shared decisionmaking is warranted, as are remote visit communication barriers and the inability to perform a full clinical exam [35].…”

Impact of the COVID-19 pandemic on clinical trials: a cross-sectional questionnaire study in China

“…We believe the application of telemedicine and some other techniques may be relevant since they minimize and offset some negative effects of the pandemic. A study conducted in the USA demonstrated that telemedicine improved accuracy and timeliness of safety event reporting since it enabled immediate, direct transmission of patients’ personal health data from home to the investigators, allowing a prompt assessment and follow-up treatment decision ( 30 ). In China, WeChat-based telemedicine has been highly recommended for remote follow-up visits during the pandemic ( 31 ).…”