Dealing with challenges in an Ebola vaccine trial in a remote and endemic Ebola setting of the Democratic Republic of the Congo
Introduction Since the discovery of the Ebola virus in 1976, the Democratic Republic of Congo has experienced 15 outbreaks of Ebola virus disease. This thesis delved into the challenges of conducting Ebola Virus Disease (EVD) vaccine trials in endemic and remote areas, focusing on the Boende Health District in the Democratic Republic of Congo (DRC). The EBL2007 vaccine trial, part of the European Union Innovative Medicines Initiative, aimed to evaluate a new Ebola vaccine regimen in a high-risk group of Healthcare providers (HCPs) and frontline workers. This research is pivotal for enhancing preparedness against potential EVD outbreaks, particularly in regions with fragile healthcare systems and limited resources. Objectives The thesis was guided by the following objectives: to evaluate the acceptability, feasibility and accuracy of an iris scanning system for identifying HCPs in the EBL2007 Ebola vaccine trial, to investigate the long-term perceptions and experiences of HCP-participants and staff regarding iris scanning technology, to identify and document the primary challenges and lessons learned from setting up an Ebola vaccine trial in a remote setting of Boende Health District in the DRC, to assess the baseline seroprevalence of antibodies against EBOV antigens among HCPs and frontline workers participants in the EBL2007 vaccine trial, to explore the HCPs-participants in the trial, trial staff, and local health authorities perception and experiences of the EBL2007, to Assess the effectiveness of the trial's information retention among participants over time, and to compile key challenges, mitigation strategies, and lessons learned from conducting the trial. Methods This doctoral thesis was centered on the EBL2007 vaccine trial, a joint initiative by the University of Antwerp and the University of Kinshasa, under the EU-IMI EBOVAC 3 project. Conducted in the Tshuapa province, DRC, from December 2019 to October 2022, the trial focused on vaccinating high-risk healthcare providers (HCPs) and frontline workers in Boende, a region previously affected by an Ebola outbreak in 2014. This setting provided a unique context to explore vaccine trial complexities in low- and middle-income countries (LMICs). The methodological approach was comprehensive, reflecting the diverse challenges of the Boende Health District. The methodologies were specifically tailored to address each research objective: iris Scanning as an biometric identification tool in the EBL2007 vaccine trial (Chapter 3): the study assessed the acceptability and accuracy of iris scanning as a biometric identification tool for HCPs using mixed methods, including focus group discussions and structured surveys. The system's performance was evaluated longitudinally, from enrollment to follow-up. Long-term Experiences with Iris Scanning (Chapter 4): A qualitative study employing phenomenological methods captured the long-term experiences and perceptions of HCP-participants and staff regarding the iris scanning system,.The study employed thematic analysis, blending inductive and deductive methods to distill themes and insights from responses in French on iris scanning in the EBL2007 vaccine trial, later translating findings into English for broader accessibility. Challenges and Lessons Learned (Chapter 5): A narrative review methodology synthesized the challenges, mitigations, and lessons learned from the trial, aiming to guide future clinical trials in similar settings. Baseline Seroprevalence of EBOV Antibodies (Chapter 6): The study analyzed baseline serum samples using FANG ELISA and Luminex assays to assess the immunogenicity and safety of Ad26.ZEBOV and MVA-BN-Filo vaccines, including statistical analyses for cutoff determination and correlation of seropositivity. Trial’s perception and experiences of participants (Chapter 7): Qualitative methods explored the trial's impact on healthcare providers, frontline workers, trial staff, and local health authorities. Data collection involved interviews and focus group discussions, analyzed using thematic approaches. Informed consent retention Assessment (Chapter 8): The trial's effectiveness in maintaining participants' understanding over time was evaluated using a Test of Understanding (TOU) at different intervals, with analysis conducted using statistical models. Documentation of challenges and mitigations in implementing the trial in a remote area of the DRC (Chapter 9): A narrative review compiled key challenges, mitigation strategies, and lessons from the trial, providing an in-depth look into the execution of the trial in a complex LMIC setting. Results A high acceptance rate of 99% was observed for iris scanning as an identification method among HCPs potential participant in the EBL2007 vaccine trial, before starting the recruitment. However, some participants expressed concerns about the potential physical harms of iris scan technology on eye. The technology accurately identified 93.1% of participants during follow-up visits, with the majority successfully identified on the first attempt and the scanning process taking 2 minutes or less. Over time, some participants reported a perception of diminished vision after using the iris scan, although no vision impairment was officially linked to the technology in the EBL2007 vaccine trial. Conducting vaccine trials in LMICs like the DRC faces numerous challenges, including complex regulatory environments, logistical and financial constraints, and the need for extensive international collaborations. Despite these obstacles, the EBOVAC 3 consortium facilitated high-quality trials in the area. The trial revealed a low seroreactivity to EBOV antigens among participants, with 1.4% showing reactivity to two EBOV-Mayinga antigens and 8.5% to GP-EBOV-Kikwit. Positive experiences were reported due to the trial’s commitment to site improvement and volunteer training. However, issues like inadequate compensation for time and travel and concerns about frequent blood draws were highlighted. Participants' understanding of the trial, assessed through a TOU scores, showed a significant decline over time (year 1 and year 2), particularly among those with less education and older participants. The trial implementation in frame of a consortium faced several challenges, including cultural differences, language barriers, and regulatory issues, requiring clear communication and adaptability among international stakeholders. Despite these challenges, the trial achieved a high participant retention rate of 92%, underscoring the importance of addressing participants’ concerns, effective communication, and flexible, collaborative approaches in vaccine trial management in remote LMIC settings. Conclusions The EBL2007 vaccine trial in Boende Health District stands as a significant achievement in clinical research for resource-limited settings. Its use of iris scanning technology, accepted by 99% of HCPs, exemplifies the effectiveness of biometric tools in ensuring trial accuracy and integrity, with a notable 93.1% success rate in participant identification. Despite some concerns over potential physical impacts, like perceived vision changes, the trial emphasizes the necessity of ongoing community engagement and clear communication. Overcoming challenges such as complex regulations and logistical hurdles, the trial achieved a remarkable 92% participant retention, thanks to the EBOVAC 3 consortium's commitment to quality, responsive volunteer training, and addressing compensation and procedural concerns. The decline in participant understanding over time, as shown in TOU scores, underscores the importance of continual education, particularly for older and less-educated participants. The EBL2007 trial demonstrates the feasibility and importance of including diverse, socio-economically disadvantaged groups in clinical research, especially in LMICs, for effective EVD response. Strategic planning, anticipation of regulatory challenges, positive local collaborations, investment in local research infrastructure, and innovative identification tools like iris scanning are crucial for enhancing trial quality and contributing to global health progress, particularly in managing EVD epidemics.
Antwerp : University of Antwerp, Faculty of Medicine and Health Sciences , 2024
241 p.
Supervisor: Van geertruyden, Jean-Pierre [Supervisor]
Supervisor: Van Damme, Pierre [Supervisor]
Supervisor: Mavoko, Hypolite Muhindo [Supervisor]
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Creation 22.04.2024
Last edited 01.05.2024
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