Lessons from the First Clinical Trial of a Non-licensed Vaccine among Ugandan Adolescents: A Phase II Field Trial of the Tuberculosis Candidate Vaccine, MVA85A

"Engagement with the community and all stakeholders was critical for successful implementation of the trial."

Despite the importance of immunisation in adolescence, and the relative ease of access via school, immunisation in late primary school is not always routine in Sub Saharan African (SSA) countries. The only licensed tuberculosis (TB) vaccine, Bacille Calmette-Guérin (BCG), prevents severe disease in childhood but does not protect against pulmonary TB among adolescents and adults in tropical latitudes. This article shares experiences and lessons learned when implementing a clinical trial of an unlicensed vaccine among adolescents in Uganda: MVA85A, a candidate TB vaccine. A key insight is that sufficient time and resources should be planned for community preparation and sensitisation to ensure buy-in and acceptance of a project of this kind.

The study was conducted with adolescents on the shores of Lake Victoria in Wakiso district in Uganda. The researchers selected schools with a high prevalence of S. mansoni based on previous surveys conducted by the Vector Control Division (VCD) of the Ministry of Health (MOH). Participants were eligible for vaccination if aged 12 to 17 years, resident in the study area, BCG-vaccinated, and healthy by history and physical examination.

Pre-trial activities included engagement with community leaders, district Ministry of Education and MOH officials, school management, and parents. At village level, the researchers held meetings with members of the Village Health Teams (VHTs), who are lay persons selected by the village and trained to provide or advise on first-aid emergency care and other health-related community initiatives. They also held meetings with the chairpersons of the Local Councils (LCs) responsible for administration of the villages. Other examples of engagement activities included participation in parents' meetings at each of the schools, which the researchers also held after screening tests were complete to seek consent, if applicable, to participate in the study. (A total of 107 participants who provided consent and assent were screened for eligibility; 36 (34%) of these were enrolled.)

Figure 1 shows a summary of the challenges encountered and solutions during pre-screening, screening, and follow-up. A discussion of lessons learned and recommendations ensues. For example, with regard to engagement of stakeholders:

• The meetings described above were a good opportunity for the team to tackle misbeliefs and rumours by providing correct information. For instance, in one of the schools, a couple of parents living in the same neighbourhood expressed a concern that prior vaccination campaigns had led to several deaths in this community. Using information from the MOH on previous vaccination campaigns in that area, the team were able to confirm that this rumour was unfounded. This information was relayed to the parents in a subsequent meeting. According to the researchers, it is important to make efforts to enhance two-way communication with communities to discuss issues that may be of concern to both the researchers and the community, and in so doing, help to close the vaccine confidence gap.
• Given the short time-frame (2-month duration of follow-up), the researchers did not establish a community advisory board (CAB), although these have become an integral part of studies with long follow-up periods. Community engagement activities, and CABs if needed, enhance community understanding of the research objectives and procedures, leading to mutual trust and a sense of collective ownership.
• All pre-trial activities and meetings were carried out alongside the VCD, which routinely delivers annual mass drug administration within this schistosomiasis-endemic area and is well known and respected in the community. As reported by others, collaborating with both government and non-government agencies already working on the ground and establishing relationships with key opinion leaders and stakeholders is essential.
• More documentation of the meetings, such as the questions and concerns raised by the parents, and whether they understood what was presented, would have been useful. The South African TB Vaccine Initiative (SATVI) used drama to engage and raise awareness of TB and clinical trials among adolescents. They followed through by assessing the impact of the drama on the adolescents. The researchers therefore recommend that sufficient time and resources should be planned for community preparation and sensitisation to ensure community buy-in and acceptance of a project of this kind, and that engagement activities are appropriately monitored and evaluated to reassure regulators and to inform future work.

The researchers also discuss their experiences with: screening pool and selection criteria; operational and logistical issues; school-specific issues; ethical and regulatory issues; and protocol and study-specific issues.

They conclude: "This study provided lessons that can be applied to other trials among adolescents in similar settings, and to school-based immunization programs. The solutions we implemented will be of value in planning other trials in this vulnerable population in Uganda and in similar settings elsewhere. This trial shows the challenges in implementing early-Phase field trials in Africa are not insurmountable and well planned ethical trials are feasible and should be encouraged."