Collecting and Reporting Adverse Events in Low-income Settings - Perspectives from Vaccine Trials in the Gambia

"[A]ccurately collecting and reporting adverse events comprehensively in vaccine clinical trials is vital to ensuring public trust in the vaccine development process..."

Clinical trials play a crucial role in assessing the efficacy and safety of medicines, vaccines, and other treatment methods before licensure. International ethical standards, including the Declaration of Helsinki and the International Council on Harmonization Guidelines for Good Clinical Practice (ICH-GCP), have been established to ensure the safety of participants. The ICH-GCP defines an adverse event as "any untoward medical occurrence in a participant administered a study product, which does not necessarily have a causal relationship with the study product itself". As a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), the authors of this paper conducted 12 vaccine trials over a 10-year period ranging in size from less than 100 to more than 3,000 participants (newborns, infants, children, and adults). Here, the researchers discuss the challenges they faced and the strategies they developed to improve the collection and reporting of adverse events in low-income settings.

Healthcare-seeking behaviours in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox health care; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. (However, when encouraging participants to avoid traditional medicines, it is crucial to approach the conversation non-judgmentally to prevent under-reporting related to social desirability and the perceived biomedical focus of the study team.) Participants are provided with mobile phones that enable them to contact the study team at any time to ask a question or report a medical concern; these phones also allow the study team to reach out for safety follow-up.

Accurate collection of adverse events offers indirect benefits to the parents, providing an opportunity for health education on optimal feeding practices and other relevant healthcare-related topics. Yet constraints in the healthcare system in the Gambia limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the MRCG maintains a Clinical Services Department that offers medical care and diagnostic services to study participants.

Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. For example, in the Gambia, a patriarchal society, women often require approval from husbands, fathers, or other significant male figures before seeking medical care for themselves or their children. These dynamics contribute to delayed reporting of adverse events when women are compelled to wait for approval from their fathers or husbands before contacting the study team. Field staff are crucial members of the team who help to mitigate these and other challenges. They collect information about adverse events during home visits on paper-based or electronic report forms. This active method of collection improves the accuracy of reported adverse events.

To ensure community engagement and support during clinical trials, community sensitisation meetings are held at the beginning of every trial, with community advisory boards increasingly playing a role in the design and set up of the studies being conducted. Community sensitisation meetings inform the community about the upcoming trial, address questions and rumours, and obtain permission from the village chief (Alkalo) and other key stakeholders to conduct research in the community. At the end of a clinical trial, open days are held to feedback the results of the trial to the community. Most members of the field team are resident in the local communities and are therefore able to detect rumours early and arrange additional community sensitisation meetings to address these rumours. According to the authors, these community engagement activities have led to routinely high recruitment and retention rates.

The authors note that the challenges they faced in collecting adverse events are not unique to the Gambia, as similar conditions are prevalent in other low-income countries. These countries often have similar health-seeking behaviours and social dynamics, weak health systems, and populations with low literacy rates. Therefore, they expect that the strategies they developed may be generally applicable to other low-income contexts.

In conclusion: "Conducting clinical research according to international ethical standards in resource-limited settings is vital but poses challenges...to ensure adverse event data are robust."

Full list of authors, with institutional affiliations: Andrew Ayi-Ashong Bruce, Medical Research Council Unit The Gambia (MRCG); Ama-Onyebuchi Umesi, MRCG; Adedapo Bashorun, MRCG; Magnus Ochoge, MRCG; Mohammed Yisa, MRCG; Dolapo Obayemi-Ajiboye, MRCG; Ahmed Futa, MRCG; Anna Njie, MRCG; Selasi Asase, MRCG; Modou Bella Jallow, MRCG; Larry Kotei, MRCG; Lucy Affleck, MRCG; Olubunmi Abiola Olubiyi, MRCG; Lamin B. Jarju, MRCG; Madi Kanyi, MRCG; Baba Danso, MRCG; Armel Zemsi, MRCG; Ed Clarke, MRCG