Algorithm for the support of non-related (serious) adverse events in an Ebola vaccine trial in the Democratic Republic of the Congo

Abstract

Implementing an Ebola vaccine trial in a remote area in the Democratic Republic of the Congo (DRC), and being confronted with a dysfunctional health care system and acute unmet health needs of participants, ethical considerations were made regarding the ancillary care obligations of the sponsor and researchers. Spurred by the occurrence of non-related (serious) adverse events (NR-SAEs), the Universities of Antwerp and Kinshasa jointly developed an algorithm, accompanied by an algorithm policy. The algorithm consists of a set of consecutive questions with binary response options, leading to structured, non-arbitrary and consistent support and management for each NR-SAE. It is the result of dialogue and collaboration between the sponsor (University of Antwerp) and the principal investigator (University of Kinshasa), consultation of literature, and input of research ethics and social sciences experts. The characteristics of the project and its budgetary framework were taken into account, as well as the local socioeconomic and healthcare situation. The algorithm and related policy have been approved by the relevant ethics committee (EC), so field implementation will begin when the study activities resume in November 2021. Lessons learnt will be shared with the relevant stakeholders within and outside DRC.If NR-SAEs are not covered by a functioning social welfare system, sponsors and researchers should develop a feasible, standardised and transparent approach to the provision of ancillary care. National legislation and contextualised requirements are therefore needed, particularly in low/middle-income countries, to guide researchers and sponsors in this process. Protocols, particularly of clinical trials conducted in areas with ‘access to care’ constraints, should include adequate ancillary care arrangements. Furthermore, it is essential that local ECs systematically require ancillary care provisions to enhance the well-being and protection of the rights of research participants. This project was funded by the European Union’s Horizon 2020 research and innovation programme, European Federation of Pharmaceutical Industries and Associations, and the Coalition for Epidemic Preparedness Innovations.

Researchers’ responsibilities in resource-constrained settings: experiences of implementing an ancillary care policy in a vaccine trial in the Democratic Republic of the Congo

“…To facilitate a non-arbitrarily approach and support the care needed for both adverse events and serious adverse events ((S)AEs) of participants, a context-specific algorithm was developed with clear criteria and decision-making principles (Lemey et al, 2021). We refer to the International Conference for Harmonization of Technical Requirements for Pharmaceuticals for Human Use to define AE and SAE as follows:…”

“…The algorithm policy was also applied retrospectively, where possible, to non-related SAEs that had occurred between the start of the trial and issuing the AC policy. The development and specific modalities of this AC approach have been described by Lemey et al (2021). The algorithm was developed through a collaborative process between the Sponsor, based in Belgium, and the PI, based in Kinshasa, DRC.…”

Setting-up an Ebola vaccine trial in a remote area of the Democratic Republic of the Congo: Challenges, mitigations, and lessons learned

“…Each challenge not only requires flexibility of the study team but often also involves a budget reshuffle. Therefore, financial risk mitigation should be part of the initial budget planning, as is considered GCP for trials conducted in resource-poor settings [35]. This way, in the course of the trial, funds could be reallocated to implement additional or unforeseen activities.…”

Boosting ethics review capacity in public health emergency situations: Co‐creation of a training model for French‐speaking research ethics committees

“…In 2020, the Democratic Republic of Congo (DRC) was hit concomitantly by measles, Ebola and COVID‐19 outbreaks, and it has a history of over two decades of natural disasters and of armed conflicts, in particular in the East. Researchers from the University of Kinshasa (UNIKIN), DRC and the Institute of Tropical Medicine (ITM) in Antwerp, Belgium, who previously collaborated in ethics reflection on informed consent and on ancillary care in clinical research in the DRC [ 25 , 26 ], partnered in 2021 with the DRC National Ethics Committee to co‐create and deliver a short training course for ethics reviewers. Based on the priority needs expressed by the partners in DRC, the training focused on ethics review of research conducted during outbreaks and other public health emergencies.…”