Considerations for Stakeholder Engagement and COVID-19 Related Clinical Trials' Conduct in sub-Saharan Africa

"Civil-society organizations, members of community advisory boards and ethics committees, young persons, COVID-19 survivors, researchers, government, and the private sector are assets for the implementation and translation of COVID-19 related clinical trials."

As the number of clinical trials (e.g., for potential vaccines and therapeutics) being conducted in sub-Saharan Africa during the COVID-19 pandemic grows, it is notable that the norms, values, and practices of collectivist societies in Sub-Saharan Africa and low research literacy pose challenges to the conduct of those trials. Perhaps instructive in this context is the Good Participatory Practice Guidelines for Emerging Pathogens (GPP-EP), whose tenets recognise that stakeholder engagement in the clinical trials could not only strengthen the epidemic response but is an ethical imperative. This study applies the GPP-EP to COVID-19-related clinical trials in sub-Saharan Africa, discussing how to lessen the gaps identified and making recommendations on facilitating adherence to the guidelines.

The essential stakeholder engagement practices enumerated in the GPP-EP include:

• Formative research - "Misinformation about COVID-19 vaccine trials is rife in the region, and it may be a barrier to the recruitment and retention of study participants." For example, there is fear that the rapid development of a vaccine could compromise the safety of any vaccine developed. "Understanding how these fears, myths, and misconceptions may disrupt study implementation, and how to address them (message and medium), is critically important..."
• A stakeholder engagement plan and a communications and issues management plan - Based on the findings of the formative research, these plans "aim to consolidate and promote relationships with a broad range of local, national, and international stakeholders such as members of representative organizations of populations eligible for the clinical trials, community leaders at clinical trial sites, civil society organizations and policy makers....Research teams that plan to implement COVID-19-related clinical trials in sub-Saharan Africa should use audiovisuals, rather than pure text, to build literacy about COVID-19 clinical trials.... Transparency and accountability are important in sub-Saharan Africa, where ethics guidelines are limited in their ability to address power inequalities that lead to voice erasures and respect for local competencies. Advocates and civil-society organizations can facilitate stakeholder engagement and communication management in ways that empower community members to work with researchers, monitor research practices, and prevent crisis in communicating the results of clinical trials."
• Protocol development - The importance of early and meaningful engagement of community members, as well as cultural considerations, in protocol development is highlighted by the debates that occurred during the conduct of clinical trials of vaccines and treatment of Ebola. It was agreed that offering experimental therapy for some community members and a placebo to others, when they all faced the same risk of death, was not acceptable. The step-wise design of the Ebola ca Suffit vaccine clinical trial "was rigorous enough to contribute data towards the vaccine licensure, yet did not take away communal access to the experimental product during the life of the intervention".
• Informed consent process - The GPP-EP holds that the informed consent document and process should be developed in collaboration with community representatives to ensure that community nuances are taken into consideration. Such an approach can help highlight key considerations such as the fact that, in sub-Saharan Africa, third parties - e.g., husbands, mothers-in-law, and community leaders - play a significant role in individuals' decision-making about their involvement in a trial. However, care should be taken that the third party does not coerce participation of another person or persons.
• Standard of prevention for vaccine research and standard of care for treatment research - The standard of prevention package for healthcare workers and home-based carers enrolled in pre- and or post-exposure prophylaxis COVID-19 trials should include personal protective equipment (PPE). The GPP-EP stresses that: "Standards of prevention and care packages for trial participants should be negotiated with community members while the protocol is being developed, and consensus should be reached on what is the best study based on evolving evidence." Decisions about standard of prevention and treatment for COVID-19 research should be developed in collaboration with the community.
• Policies on trial-related physical, psychological, financial, and/or social harms - "The health systems in many countries in sub-Saharan Africa are weak, with difficulties in meeting the care needs of COVID-19 trial participants who may have trial-related injuries..." Thus, per the GPP-EP, policies on harm should be negotiated - with attention paid to individuals or groups who may be vulnerable, marginalised, and/or stigmatised. 
• Trial accrual, follow-up, exit trial closure, results dissemination, and post-trial access to trial products or procedures - These matters "should be discussed with stakeholders, who can provide pertinent information on how to design socially and culturally acceptable strategies. Plans for disseminating the results of trials and strategies to manage expectations about trial results should be laid. Lessons from research on biomedical HIV prevention have shown how planning for the dissemination of trial results to stakeholders can endear continued public support for the research, despite multiple failures. At trial closure, community members are taken through possible trial outcomes, open discussions about the implications of the results are held, and consensus is reached on the next line of action. This approach has helped prevent the proliferation of negative stories about failed HIV prevention trials and, rather, helped maintain support for investment in trials."

Because "[t]he power imbalance between researchers and community members in sub-Saharan Africa makes voice erasure possible," the researchers suggest encouraging community monitoring of clinical trials, whereby "community members collect and analyze data about the clinical trial being implemented and use the information to advocate for change if it is needed....Many civil societies in Africa have developed competencies to conduct community-led monitoring programs for HIV, tuberculosis, and malaria programs in the region. This civil-society role should be applied to the monitoring of COVID-19 clinical trials, but it is not discussed in the GPP-EP....Support for civil societies to monitor COVID-19 clinical trials and regularly report their findings to ethics committees should enable them to determine that clinical trials are important and should be pursued."

Specifically, the researchers recommend the formation of community advisory boards (CABs) made up of representatives from the communities where research is taking place - especially COVID-19 survivors and representatives of youth groups. "The CAB can strengthen relationships between researchers and the community; educate community members about the research; and review research protocols, study materials, and informed consent tools, with the aim of ensuring that socio-cultural contexts and concerns are addressed when designing and conducting the studies and disseminating the findings."

In conclusion: "Africa is not new to the conduct of clinical trials, and it has made successes of many of the clinical trials conducted on the continent through robust stakeholder engagement....Documented successes with COVID-19 clinical trials will help in achieving stakeholder engagement in future trials to be conducted in the region."