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.

BACKGROUND

Conflict is known to impact maternal and neonatal health in Eastern Democratic Republic of the Congo (DRC), an area of longstanding insecurity. We conducted a systematic review on pregnancy and neonatal outcomes in this region to provide a comprehensive overview of maternal and neonatal outcomes over a 20-year period.

METHODS

We systematically searched databases, such as Medline, EMBASE, Global Health, ClinicalTrials.gov and the Cochrane Library, along with grey literature, for articles published between 2001 and 2021. These articles provided quantitative data on selected pregnancy and neonatal outcomes in the provinces of Ituri, Maniema and North and South Kivu, Eastern DRC. We conducted a descriptive analysis, combining results from different data sources and comparing incidence of outcomes in North Kivu with those in other provinces in Eastern DRC.

RESULTS

A total of 1,065 abstracts from peer-reviewed publications and 196 articles from the grey literature were screened, resulting in the inclusion of 14 scientific articles in the review. The most frequently reported pregnancy complications were caesarean sections (11.6%–48.3% of deliveries) and miscarriage (1.2%–30.0% of deliveries). The most common neonatal outcomes were low birth weight (3.8%–21.9% of live births), preterm birth (0.9%–74.0%) and neonatal death (0.2%–43.3%).

CONCLUSION

Our review provides data on pregnancy and neonatal outcomes in Eastern DRC, which will be valuable for future studies. Despite the area's ongoing armed conflict, the percentages of complications we noted in Eastern DRC are comparable with those observed in other countries in the region.

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.

Research, especially clinical trials, during outbreaks often poses enormous challenges, and up until very recent times was often considered almost impossible. However, for diseases such as Ebola virus disease, which are seen almost exclusively in outbreak form, outbreaks are the only opportunity to perform studies and accrue knowledge. Here, we discuss our experiences and lessons learned implementing a clinical study of an Ebola virus vaccine during an outbreak of that disease in 2018–20 in eastern Democratic Republic of the Congo. Keys to success is these settings include forging partnerships with diverse and complementary experience and skills, working out clear roles and responsibilities, communicating and engaging with the community as an essential partner, and maintaining flexibility to adapt to unexpected events. Progress in these complex settings requires both quick action to implement studies as soon as possible, coupled with patience, realizing that results often come with a sequential long-term approach across outbreaks as opportunities arise. Despite the many challenges, where the political will is there and the right team assembled, significant progress can be made, contributing both to control of the present outbreak and prevention or enhanced control of the next one.