{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:23:05Z","timestamp":1783347785707,"version":"3.54.6"},"reference-count":39,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"unspecified","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,5,24]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"\n Background<\/jats:title>\n \n Preparedness for emerging pathogens can be strengthened by leveraging lessons from COVID-19 therapeutic trials. The COVERAGE Africa trial (\n NCT04920838<\/jats:ext-link>\n , ANRS033, 2021\u201322), 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\u2019s implementation and to identify the factors that influence it.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The PEARLES framework was applied to identify and classify indicators related to political, economic, administrative, regulatory, logistical, ethical and societal factors influencing trial\u2019s 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\u2014supporting the trial\u2019s execution as planned\u2014or barriers\u2014causing delays, hindering progress or leading to deviations.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Barriers to trial implementation included: (1) the trial\u2019s 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\u2019 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\u2019s implementation.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n To 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-109889","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:30:06Z","timestamp":1783344606000},"page":"e109889","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct04920838","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04920838","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04920838","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04920838","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7511-7527","authenticated-orcid":false,"given":"Mwinmalo In\u00e8s Evelyne","family":"Da","sequence":"first","affiliation":[{"name":"National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Talence, Nouvelle-Aquitaine, France"},{"name":"Department of Infectious Diseases, Centre MURAZ, Bobo-Dioulasso, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8971-6878","authenticated-orcid":false,"given":"M\u00e9lanie","family":"Plazy","sequence":"additional","affiliation":[{"name":"National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Talence, Nouvelle-Aquitaine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0069-3332","authenticated-orcid":false,"given":"Anthony","family":"L\u2019hostellier","sequence":"additional","affiliation":[{"name":"National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Talence, Nouvelle-Aquitaine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Malvy","sequence":"additional","affiliation":[{"name":"National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Talence, Nouvelle-Aquitaine, France"},{"name":"Department of Infectious Diseases and Tropical Medicine, Division of Tropical Medicine and Clinical International Health, CHU Bordeaux GH Pellegrin, Bordeaux, Nouvelle-Aquitaine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3350-112X","authenticated-orcid":false,"given":"Olivier","family":"Marcy","sequence":"additional","affiliation":[{"name":"National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Talence, Nouvelle-Aquitaine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdramane","family":"Berthe","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Centre MURAZ, Bobo-Dioulasso, Burkina Faso"},{"name":"University of Daniel Ouezzin Coulibaly (UDOC), Dedougou, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anselme","family":"Sanon","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Centre MURAZ, Bobo-Dioulasso, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Fritzell","sequence":"additional","affiliation":[{"name":"National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Talence, Nouvelle-Aquitaine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoul-Salam","family":"Ouedraogo","sequence":"additional","affiliation":[{"name":"Bacteriology\u2013Virology Laboratory, University Hospital Sanou Souro, Bobo-Dioulasso, Hauts-Bassins Region, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armel","family":"Poda","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Centre MURAZ, Bobo-Dioulasso, Burkina Faso"},{"name":"Department of Infectious and Tropical Diseases, Sourou Sanou University Hospital Center, Bobo-Dioulasso, Hauts-Bassins Region, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Duvignaud","sequence":"additional","affiliation":[{"name":"National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Talence, Nouvelle-Aquitaine, France"},{"name":"Department of Infectious Diseases and Tropical Medicine, Division of Tropical Medicine and Clinical International Health, CHU Bordeaux GH Pellegrin, Bordeaux, Nouvelle-Aquitaine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-4089","authenticated-orcid":false,"given":"Joanna","family":"Orne-Gliemann","sequence":"additional","affiliation":[{"name":"National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Talence, Nouvelle-Aquitaine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"2026070606101491000_16.7.e109889.1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/PHH.0000000000001879","article-title":"Evidence-Based Strategies to Enhance Public Health Emergency Preparedness and Response","volume":"30","author":"Peterson","year":"2024","journal-title":"Journal of Public Health Management & Practice"},{"key":"2026070606101491000_16.7.e109889.2","first-page":"341","article-title":"Difficulties with conducting clinical trials in France","volume":"56","author":"Zannad","year":"2001","journal-title":"Therapie"},{"key":"2026070606101491000_16.7.e109889.3","doi-asserted-by":"crossref","DOI":"10.1001\/jamahealthforum.2023.3191","article-title":"Strategies for Expediting Clinical Trials in the Next Public Health Emergency","volume":"4","author":"Titanji","year":"2023","journal-title":"JAMA Health Forum"},{"key":"2026070606101491000_16.7.e109889.4","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/S0140-6736(10)60068-2","article-title":"Research funding in a pandemic","volume":"375","author":"Walley","year":"2010","journal-title":"The Lancet"},{"key":"2026070606101491000_16.7.e109889.5","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/S0140-6736(17)31602-1","article-title":"Clinical trials during epidemics","volume":"389","author":"Keusch","year":"2017","journal-title":"The Lancet"},{"key":"2026070606101491000_16.7.e109889.6","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-021-06214-4","article-title":"Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews","volume":"21","author":"Borges do Nascimento","year":"2021","journal-title":"BMC Infect Dis"},{"key":"2026070606101491000_16.7.e109889.7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0302755","article-title":"Informed consent and trial prioritization for clinical studies during the COVID-19 pandemic. Stakeholder experiences and viewpoints","volume":"19","author":"Weigold","year":"2024","journal-title":"PLoS ONE"},{"key":"2026070606101491000_16.7.e109889.8","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11673-023-10309-9","article-title":"The Case for Human Challenge Trials in COVID-19","volume":"21","author":"Drewett","year":"2024","journal-title":"J Bioeth Inq"},{"key":"2026070606101491000_16.7.e109889.9","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/bioe.13326","article-title":"Virtue ethics and the unsettled ethical questions in controlled human infection studies","volume":"38","author":"Poomkudy","year":"2024","journal-title":"Bioethics"},{"key":"2026070606101491000_16.7.e109889.10","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/inm.13251","article-title":"Interventions to reduce burnout and improve the mental health of nurses during the COVID-19 pandemic: A systematic review of randomised controlled trials with meta-analysis","volume":"33","author":"Wong","year":"2024","journal-title":"Int J Ment Health Nurs"},{"key":"2026070606101491000_16.7.e109889.11","doi-asserted-by":"crossref","DOI":"10.3389\/fpubh.2023.1231266","article-title":"Interventions to reduce stress and prevent burnout in healthcare professionals supported by digital applications: a scoping review","volume":"11","author":"Adam","year":"2023","journal-title":"Front Public Health"},{"key":"2026070606101491000_16.7.e109889.12","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.idc.2021.07.008","article-title":"Pandemic Preparedness","volume":"35","author":"Godshall","year":"2021","journal-title":"Infect Dis Clin North Am"},{"key":"2026070606101491000_16.7.e109889.13","unstructured":"National Library of Medicine . Home | clinicaltrials.gov. 2024. Available: https:\/\/clinicaltrials.gov\/ [Accessed 4 Sep 2024]."},{"key":"2026070606101491000_16.7.e109889.14","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2022.51974","article-title":"Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials","volume":"6","author":"Mena Lora","year":"2023","journal-title":"JAMA Netw Open"},{"key":"2026070606101491000_16.7.e109889.15","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1177\/1740774518780678","article-title":"EBOVAC-Salone: Lessons learned from implementing an Ebola vaccine trial in an Ebola-affected country","volume":"15","author":"Mooney","year":"2018","journal-title":"Clin Trials"},{"key":"2026070606101491000_16.7.e109889.16","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1093\/infdis\/jix657","article-title":"Implementing a Multisite Clinical Trial in the Midst of an Ebola Outbreak: Lessons Learned From the Sierra Leone Trial to Introduce a Vaccine Against Ebola","volume":"217","author":"Carter","year":"2018","journal-title":"J Infect Dis"},{"key":"2026070606101491000_16.7.e109889.17","unstructured":"ANRS, Emerging Infectious Diseases . Early Treatment of Vulnerable Individuals With Non-Severe SARS-CoV-2 Infection: A Multi-Arm Multi-Stage Randomized Trial (MAMS) to Evaluate the Effectiveness of Several Specific Treatments in Reducing the Risk of Clinical Worsening or Death in Sub-Saharan Africa (COVERAGE-Africa). clinicaltrials.gov; 2023. Available: https:\/\/clinicaltrials.gov\/study\/NCT04920838 [accessed 11 Aug 2025]"},{"key":"2026070606101491000_16.7.e109889.18","unstructured":"ANTICOV trial. Available: https:\/\/anticov.org\/about-anticov\/ [Accessed 21 Feb 2024]."},{"key":"2026070606101491000_16.7.e109889.19","doi-asserted-by":"crossref","DOI":"10.1080\/07853890.2023.2222641","article-title":"The COVID-19 experience in Africa and the Middle East","volume":"55","author":"Bizri","year":"2023","journal-title":"Ann Med"},{"key":"2026070606101491000_16.7.e109889.20","doi-asserted-by":"crossref","DOI":"10.1186\/s12889-019-7978-4","article-title":"Lessons learned from engaging communities for Ebola vaccine trials in Sierra Leone: reciprocity, relatability, relationships and respect (the four R\u2019s)","volume":"19","author":"Dada","year":"2019","journal-title":"BMC Public Health"},{"key":"2026070606101491000_16.7.e109889.21","doi-asserted-by":"crossref","DOI":"10.1186\/s43058-025-00712-1","article-title":"Key determinants in implementation processes: a systematic review using the Consolidated Framework for Implementation Research (CFIR)","volume":"6","author":"Schmitt","year":"2025","journal-title":"Implement Sci Commun"},{"key":"2026070606101491000_16.7.e109889.22","doi-asserted-by":"crossref","DOI":"10.1093\/jncics\/pkab027","article-title":"Barriers and Facilitators to Adolescent and Young Adult Cancer Trial Enrollment: NCORP Site Perspectives","volume":"5","author":"Siembida","year":"2021","journal-title":"JNCI Cancer Spectr"},{"key":"2026070606101491000_16.7.e109889.23","unstructured":"WHO Seventy-eighth World Health Assembly . WHO pandemic agreement. Gen\u00e8ve World Health Organization; 2025.1\u201335."},{"key":"2026070606101491000_16.7.e109889.24","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jcrc.2017.02.009","article-title":"Time required to initiate outbreak and pandemic observational research","volume":"40","author":"Rishu","year":"2017","journal-title":"J Crit Care"},{"key":"2026070606101491000_16.7.e109889.25","doi-asserted-by":"crossref","DOI":"10.1186\/s13690-022-00999-9","article-title":"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)","volume":"80","author":"Grenier","year":"2022","journal-title":"Arch Public Health"},{"key":"2026070606101491000_16.7.e109889.26","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/S0140-6736(15)00946-0","article-title":"Will Ebola change the game? Ten essential reforms before the next pandemic. The report of the Harvard-LSHTM Independent Panel on the Global Response to Ebola","volume":"386","author":"Moon","year":"2015","journal-title":"The Lancet"},{"key":"2026070606101491000_16.7.e109889.27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsb1209510"},{"key":"2026070606101491000_16.7.e109889.28","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.b4652","article-title":"Future of flu vaccines. Expediting clinical trials in a pandemic","volume":"339","author":"Pollard","year":"2009","journal-title":"BMJ"},{"key":"2026070606101491000_16.7.e109889.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2016.03.008"},{"key":"2026070606101491000_16.7.e109889.30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.35772\/ghm.2023.01022","article-title":"Clinical trial experience in Japan and future issues in developing drugs to treat COVID-19","volume":"5","author":"Mikami","year":"2023","journal-title":"Glob Health Med"},{"key":"2026070606101491000_16.7.e109889.31","doi-asserted-by":"crossref","DOI":"10.1017\/dmp.2023.50","article-title":"Barriers and Enablers to Using an Emergency Operations Center in Public Health Emergency Management: A Scoping Review","volume":"17","author":"Allen","year":"2023","journal-title":"Disaster Med Public Health Prep"},{"key":"2026070606101491000_16.7.e109889.32","doi-asserted-by":"crossref","DOI":"10.1183\/23120541.00227-2018","article-title":"Advancing preparedness for clinical research during infectious disease epidemics","volume":"5","author":"Gobat","year":"2019","journal-title":"ERJ Open Res"},{"key":"2026070606101491000_16.7.e109889.33","doi-asserted-by":"crossref","DOI":"10.3389\/fdata.2023.1355080","article-title":"Trends of the COVID-19 dynamics in 2022 and 2023 vs. the population age, testing and vaccination levels","volume":"6","author":"Nesteruk","year":"2023","journal-title":"Front Big Data"},{"key":"2026070606101491000_16.7.e109889.34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0281342","article-title":"Knowledge, attitude and perception towards COVID-19 among representative educated sub-Saharan Africans: A cross-sectional study during the exponential phase of the pandemic","volume":"19","author":"Udoakang","year":"2024","journal-title":"PLoS One"},{"key":"2026070606101491000_16.7.e109889.35","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0249853","article-title":"Knowledge, attitude, perception, and preventative practices towards COVID-19 in sub-Saharan Africa: A scoping review","volume":"16","author":"Nwagbara","year":"2021","journal-title":"PLoS ONE"},{"key":"2026070606101491000_16.7.e109889.36","doi-asserted-by":"crossref","first-page":"542","DOI":"10.4314\/ahs.v22i3.59","article-title":"Knowledge, risk-perception, and uptake of COVID-19 prevention measures in sub-Saharan Africa: a scoping review","volume":"22","author":"Matovu","year":"2022","journal-title":"Afr Health Sci"},{"key":"2026070606101491000_16.7.e109889.37","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2022-061715","article-title":"Perceptions of COVID-19 among communities of Conakry (Guinea): a qualitative study exploring the context of the ANRS COV33 Coverage-Africa therapeutic trial","volume":"12","author":"Doucet","year":"2022","journal-title":"BMJ Open"},{"key":"2026070606101491000_16.7.e109889.38","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.conctc.2016.06.008","article-title":"Beating the Odds: Successful Establishment of a Phase II\/III Clinical Research Trial in Resource-Poor Liberia during the Largest-Ever Ebola Outbreak","volume":"4","author":"Doe-Anderson","year":"2016","journal-title":"Contemp Clin Trials Commun"},{"key":"2026070606101491000_16.7.e109889.39","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-015-0950-8","article-title":"Stakeholders\u2019 engagement with Ebola therapy research in resource limited settings","volume":"15","author":"Folayan","year":"2015","journal-title":"BMC Infect Dis"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-109889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:30:20Z","timestamp":1783344620000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-109889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,6]]},"published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1136\/bmjopen-2025-109889"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-109889","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]}}}