Investigation of barriers and facilitators to implementing a randomised controlled trial during health emergency using the PEARLES framework: insights from the coverage Africa trial on COVID-19 treatments in Burkina Faso.

backgroundPreparedness for emerging pathogens can be strengthened by leveraging lessons from COVID-19 therapeutic trials. The COVERAGE Africa trial (NCT04920838, ANRS033, 2021-22), one of the few COVID-19 therapeutics trials conducted in resource-limited settings, sought to identify early treatment strategies for ambulatory patients at-risk for severe disease in Guinea and Burkina Faso. This implementation research, based on secondary data from the Burkina Faso sites, aimed to document the trial's implementation and to identify the factors that influence it.

methodsThe PEARLES framework was applied to identify and classify indicators related to political, economic, administrative, regulatory, logistical, ethical and societal factors influencing trial's implementation. Data drawn from regulatory documents, weekly internal reports, financial documents, programmatic data, equipment receipt slips, contracts and logistical documents, as well as the dynamic of recruitment in the trial were analysed to describe these indicators as either facilitators-supporting the trial's execution as planned-or barriers-causing delays, hindering progress or leading to deviations.

resultsBarriers to trial implementation included: (1) the trial's adaptive design, needing iterative protocol amendments leading to regulatory delays that were aggravated by the misalignment between national and international care guidelines, (2) funding disbursement lags, (3) challenges in participants' enrolment due to inadequate screening sites organisation that compromised patient confidentiality and (4) significant increase in the refusal rate during the trial, rising from 3% in 2021 to 38% in 2022. Despite these constraints, mitigation strategies such as prefinancing, mobile team deployment and site renovations enabled effective trial delivery. Strong governmental support, rapid mobilisation of funders and flexibility in staff deployment facilitated trial's implementation.

conclusionTo enhance trial readiness in emergency situations, countries need political commitment, preapproved protocols, dedicated research infrastructure and rapid funding mechanisms. Stakeholder engagement and preparedness exercises are essential to strengthen clinical trial capacity in low-resource settings particularly across sub-Saharan Africa.