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)

Abstract

Background The emergency set-up and implementation of outpatient clinical trials on epidemic emerging infectious diseases such as COVID-19 raise many issues in terms of research structuration, regulations, and health systems organization. We aimed to describe the experience and points of view of different stakeholders involved in a French home-based outpatient trial on COVID-19 and to identify the early barriers and facilitators to the trial implementation. Methods We conducted a mixed-methods study in July 2020. A self-administered questionnaire was emailed to 213 clinical, operational and research stakeholders involved in the Coverage trial; individual semi-directed interviews were conducted among 14 stakeholders. Questionnaire data and written interview notes are presented together by key theme. Results One hundred fifty six stakeholders responded to the questionnaire. 53.4% did not have prior experience in clinical research. The motivation of most stakeholders to participate in the Coverage trial was to feel useful during the pandemic. 87.9% agreed that the trial had an unusual set-up timeframe, and many regretted a certain lack of regulatory flexibility. Mobile medical teams and specific professional skills were perceived as instrumental for outpatient research. Conclusions The implementation of a home-based outpatient clinical trial on COVID-19 was perceived as relevant and innovative although requiring important adaptations of usual professional responsibilities and standard research procedures. Lessons learned from the Coverage trial underline the need for improved networks between hospital and community medicine, and call for a dedicated and reactive outpatient research platform on emerging or threatening infectious diseases.

Individual Patient Data Meta-Analysis evaluating Camostat Mesilate to Treat COVID-19 in Community Settings

“…The search for effective preventive and therapeutic treatments against COVID-19 in outpatient clinical trials is challenging with regard to constructional and organizational issues as well as within constantly shifting landscapes from changing virus variants to rise and fall in incidence. 25 Recruitment slowed in all the present individual studies in parallel with the roll-out of the COVID-19 vaccination campaign along with the introduction of monoclonal antibodies and other therapeutics that perturbed equipoise and made placebo control ethically unacceptable.…”

The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice

“…Regulatory bodies were reluctant to grant approval for a study with an unregistered product in general practice, even when the unregistered product (camostat) had been in use for more than 3 decades in Asia with an excellent safety profile. This chimes with the experience in the COVERAGE trial, a platform trial conducted in France evaluating telmisartan, inhaled ciclesonide and interferon ß-1b, where stakeholders felt that regulatory processes were not well adapted to the general practice context (15). Trials in general practice could benefit from the creation of a general practice Clinical Trial Centre (CTC) where all regulatory processes are controlled and general practice expertise is developed.…”

Molecular hydrogen for outpatients with Covid-19 (Hydro-Covid): a phase 3, randomised, triple-blinded, adaptive, placebo-controlled, multicentre trial

“…The COVID-19 clinical trials have had a leverage effect in getting research out of hospital centers and proposing organizational innovations to reach out to patients in their own environment. As a case in point, the COVERAGE platform trial involved 213 stakeholders in setting up and running the clinical trial for 1 investigating center (33). Of these, more than half were the mobile teams responsible for the inclusion and home follow-up of the included patients.…”