Feedback of research findings for vaccine trials: experiences from two malaria vaccine trials involving healthy children on the Kenyan Coast.

Internationally, calls for feedback of findings to be made an 'ethical imperative' or mandatory have been met with both strong support and opposition. Challenges include differences in issues by type of study and context, disentangling between aggregate and individual study results, and inadequate empirical evidence on which to draw. In this paper we present data from observations and interviews with key stakeholders involved in feeding back aggregate study findings for two Phase II malaria vaccine trials among children under the age of 5 years old on the Kenyan Coast. In our setting, feeding back of aggregate findings was an appreciated set of activities. The inclusion of individual results was important from the point of view of both participants and researchers, to reassure participants of trial safety, and to ensure that positive results were not over-interpreted and that individual level issues around blinding and control were clarified. Feedback sessions also offered an opportunity to re-evaluate and re-negotiate trial relationships and benefits, with potentially important implications for perceptions of and involvement in follow-up work for the trials and in future research. We found that feedback of findings is a complex but key step in a continuing set of social interactions between community members and research staff (particularly field staff who work at the interface with communities), and among community members themselves; a step which needs careful planning from the outset. We agree with others that individual and aggregate results need to be considered separately, and that for individual results, both the nature and value of the information, and the context, including social relationships, need to be taken into account.

Beginning community engagement at a busy biomedical research programme: experiences from the KEMRI CGMRC-Wellcome Trust Research Programme, Kilifi, Kenya.

There is wide acknowledgement of the need for community engagement in biomedical research, particularly in international settings. Recent debates have described theoretical approaches to identifying situations where this is most critical and potential mechanisms to achieve it. However, there is relatively little published experience of community engagement in practice. A major component of the Kenya Medical Research Institute (KEMRI) Wellcome Trust Research Programme is centred on Kilifi District General Hospital and surrounding community of 240,000 local residents. Documented community perceptions of the research centre are generally positive, but many indicate a low understanding of research and therapeutic misconceptions of its activities. As in other settings, these misunderstandings have contributed to concerns and rumours, and potentially undermine ethical aspects of research and local trust in the institution. Through a series of consultative activities, a community engagement strategy has been developed in Kilifi to strengthen mutual understanding between community members and the Centre. One important component is the establishment of a representative local resident network in different geographic locations commonly involved in research, to supplement existing communication channels. Early implementation of the strategy has provided new and diverse opportunities for dialogue, interaction and partnership building. Through the complex social interactions inherent in the community engagement strategy, the centre aims to build context specific ethical relations with local residents and to strengthen understanding of how ethical principles can be applied in practice. Evaluations over time will assess the effectiveness and sustainability of these strategies, provide generalisable information for similar research settings, and contribute to debates on the universality of ethical principles for research. This paper aims to summarise the rationale for community engagement in research, drawing on published literature and local findings, to outline the process of community engagement in Kilifi and to describe issues emerging from its development and early implementation.

Taking social relationships seriously: lessons learned from the informed consent practices of a vaccine trial on the Kenyan Coast.

Individual informed consent is a key ethical obligation for clinical studies, but empirical studies show that key requirements are often not met. Common recommendations to strengthen consent in low income settings include seeking permission from community members through existing structures before approaching individuals, considering informed consent as a process rather than a single event, and assessing participant understanding using questionnaires. In this paper, we report on a qualitative study exploring community understanding and perceptions of a malaria vaccine trial (MVT) conducted in a rural setting on the Kenyan Coast. The MVT incorporated all of the above recommendations into its information-giving processes. The findings support the importance of community level information-giving and of giving information on several different occasions before seeking final individual consent. However, an emerging issue was that inter-personal interactions and relationships between researchers and community members, and within the community, play a critical role in participants' perceptions of a study, their decisions to consent or withdraw, and their advice to researchers on study practicalities and information to feedback at the end of the trial. These relationships are based on and continually tested by information-giving processes, and by context specific concerns and interests that can be difficult to predict and are well beyond the timescale and reach of single research activities. On the basis of these findings, we suggest that the current move towards increasingly ambitious and stringent formal standards for information-giving to individuals be counter-balanced with greater attention to the diverse social relationships that are essential to the successful application of these procedures. This may be assisted by emphasising respecting communities as well as persons, and by recognising that current guidelines and regulations may be an inadequate response to the complex, often unpredictable and ever shifting ethical dilemmas facing research teams working 'in the field'.

Incorporating a quiz into informed consent processes: qualitative study of participants' reactions.

BACKGROUND: Formal checks of participant understanding are now widely recommended to improve informed consent processes. However, the views of the participants these assessments are designed to protect are rarely considered. In this paper the findings of a qualitative study aimed at documenting community reactions to a semi-structured questionnaire ('quiz') are reported. The quiz was administered to 189 mothers after consenting for their children to participate in a malaria vaccine trial on the Kenyan Coast. METHODS: Once the malaria vaccine trial was underway, focus group discussions were held with some of these mothers (nine groups; 103 mothers), and with community-based field staff attached to the malaria vaccine trial (two groups of five workers). Individual interviews with other trial staff were also held. RESULTS: The quiz prompted community members to voice concerns about blood sampling and vaccine side-effects, thereby encouraging additional discussions and interactions between the research team and potential study participants. However, it also caused significant upset and concern. Some of the quiz questions, or the way in which they were asked, appeared to fuel misconceptions and fears, with potentially negative consequences for both the study and community members. CONCLUSION: Formal approaches to checking study understanding should be employed with sensitivity and caution. They are influenced by and impact upon complex social relationships between and among researchers and community members. Adequate consideration of these contexts in assessments of understanding, and in responding to the issues raised, requires strong social science capacity.

A phase 2b randomised trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya.

OBJECTIVE: The objective was to measure the efficacy of the vaccination regimen FFM ME-TRAP in preventing episodes of clinical malaria among children in a malaria endemic area. FFM ME-TRAP is sequential immunisation with two attenuated poxvirus vectors (FP9 and modified vaccinia virus Ankara), which both deliver the pre-erythrocytic malaria antigen construct multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). DESIGN: The trial was randomised and double-blinded. SETTING: The setting was a rural, malaria-endemic area of coastal Kenya. PARTICIPANTS: We vaccinated 405 healthy 1- to 6-year-old children. INTERVENTIONS: Participants were randomised to vaccination with either FFM ME-TRAP or control (rabies vaccine). OUTCOME MEASURES: Following antimalarial drug treatment children were seen weekly and whenever they were unwell during nine months of monitoring. The axillary temperature was measured, and blood films taken when febrile. The primary analysis was time to a parasitaemia of over 2,500 parasites/mul. RESULTS: The regime was moderately immunogenic, but the magnitude of T cell responses was lower than in previous studies. In intention to treat (ITT) analysis, time to first episode was shorter in the FFM ME-TRAP group. The cumulative incidence of febrile malaria was 52/190 (27%) for FFM ME-TRAP and 40/197 (20%) among controls (hazard ratio = 1.52). This was not statistically significant (95% confidence interval [CI] 1.0-2.3; p = 0.14 by log-rank). A group of 346 children were vaccinated according to protocol (ATP). Among these children, the hazard ratio was 1.3 (95% CI 0.8-2.1; p = 0.55 by log-rank). When multiple malaria episodes were included in the analyses, the incidence rate ratios were 1.6 (95% CI 1.1-2.3); p = 0.017 for ITT, and 1.4 (95% CI 0.9-2.1); p = 0.16 for ATP. Haemoglobin and parasitaemia in cross-sectional surveys at 3 and 9 mo did not differ by treatment group. Among children vaccinated with FFM ME-TRAP, there was no correlation between immunogenicity and malaria incidence. CONCLUSIONS: No protection was induced against febrile malaria by this vaccine regimen. Future field studies will require vaccinations with stronger immunogenicity in children living in malarious areas.