Clinical trials in settings with intermittent or non-existent internet and power connectivity, for example during humanitarian emergencies, present challenges in the synchronisation of data across different sites, in addition to accessing a centralised database in real-time. To overcome these, we designed a novel hybrid analogue/digital data management system which was deployed during the rapid implementation of a Phase III evaluation of a two-dose preventative vaccine for Ebola virus disease in Goma, Democratic Republic of the Congo, from 2019 to 2022. We provided study participants with an Enhanced Participant Record Card (EPRC) that served as eligibility for, and confirmation of, vaccination and was used in combination with Open Data Kit (ODK) electronic case report forms to create an off-grid study participant management system. To understand the utility of the EPRC, we analysed data from 15,327 study participants who received both vaccines and various types of prompts or reminders to return for dose 2, including home visits, telephone calls, or short messaging service (SMS). A total of 53% participants referred to the date on the EPRC as a prompt to return for dose 2 and 36.1% mentioned this as the only prompt. A multivariable generalised linear mixed-effects model showed that those who were not working, those aged 45–64 years or who had a chronic medical condition identified prior to receiving dose 2 were more likely to use the date on the EPRC as a prompt. Our findings demonstrate the utility of this system in the facilitation of decentralised data collection in off-grid locations that may be useful for future trials in complex humanitarian settings.

During the 2018–2020 Ebola virus disease outbreak in Democratic Republic of the Congo, a phase 3 trial of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine (DRC-EB-001) commenced in Goma, with participants being offered the two-dose regimen given 56 days apart. Suspension of trial activities in 2020 due to the COVID-19 pandemic led to some participants receiving a late dose 2 outside the planned interval. Blood samples were collected from adults, adolescents, and children prior to their delayed dose 2 vaccination and 21 days after, and tested for IgG binding antibodies against Ebola virus glycoprotein using the Filovirus Animal Nonclinical Group (FANG) ELISA. Results from 133 participants showed a median two-dose interval of 9.3 months. The pre-dose 2 antibody geometric mean concentration (GMC) was 217 ELISA Units (EU)/mL (95% CI 157; 301) in adults, 378 EU/mL (281; 510) in adolescents, and 558 EU/mL (471; 661) in children. At 21 days post-dose 2, the GMC increased to 22,194 EU/mL (16,726; 29,449) in adults, 37,896 EU/mL (29,985; 47,893) in adolescents, and 34,652 EU/mL (27,906; 43,028) in children. Participants receiving a delayed dose 2 had a higher GMC at 21 days post-dose 2 than those who received a standard 56-day regimen in other African trials, but similar to those who received the regimen with an extended interval.

During the 2018–2020 Ebola virus disease (EVD) outbreak, residents in Goma, Democratic Republic of the Congo, were offered a two-dose prophylactic EVD vaccine. This was the first study to evaluate the safety of this vaccine in pregnant women. Adults, including pregnant women, and children aged ≥1 year old were offered the Ad26.ZEBOV (day 0; dose 1), MVA-BN-Filo (day 56; dose 2) EVD vaccine through an open-label clinical trial. In total, 20,408 participants, including 6635 (32.5%) children, received dose 1. Fewer than 1% of non-pregnant participants experienced a serious adverse event (SAE) following dose 1; one SAE was possibly related to the Ad26.ZEBOV vaccine. Of the 1221 pregnant women, 371 (30.4%) experienced an SAE, with caesarean section being the most common event. No SAEs in pregnant women were considered related to vaccination. Of 1169 pregnancies with a known outcome, 55 (4.7%) ended in a miscarriage, and 30 (2.6%) in a stillbirth. Eleven (1.0%) live births ended in early neonatal death, and five (0.4%) had a congenital abnormality. Overall, 188/891 (21.1%) were preterm births and 79/1032 (7.6%) had low birth weight. The uptake of the two-dose regimen was high: 15,328/20,408 (75.1%). The vaccine regimen was well-tolerated among the study participants, including pregnant women, although further data, ideally from controlled trials, are needed in this crucial group.