Exploring communication strategies that promote sound informed consent for HIV vaccine trials.

Master of Social Science in Health Research Ethics. University of KwaZulu-Natal, Pietermaritzburg 2017.The development of an HIV vaccine is a foremost universal health priority, necessitating research with human volunteers. It has been internationally accepted that informed consent is a fundamental ethical requirement for all clinical trials, including HIV vaccine trials (HVTs). However prospective trial participants often demonstrate a lack of understanding of information conveyed to them during the informed consent process. Ways of communicating complex concepts may need to be identified and developed to promote understanding. This study had the following aims: (a) To explore communication strategies reportedly implemented by key HIV vaccine trial stakeholders to communicate key concepts (Community Advisory Board or CAB members, Educators, Consent Counsellors) b) To explore correspondence between reported strategies and recommendations from the conceptual and empirical literature, and c) To explore the implications for strengthening informed consent for research in resource- constrained settings. The study comprised an analysis of four Focus Group Discussions with key stakeholders at an HIV vaccine trial site in South Africa, that had been previously conducted by members of the HIV AIDS Vaccines Ethics Group from the University of KwaZulu-Natal (UKZN). These stakeholders included CAB members who interacted with participating-community members; Educators who interacted with interested community members at the site, and Consent Counsellors who interacted with persons interested in enrolment in actual HIV vaccine trials. These transcripts were analysed using Thematic Analysis, informed by aspects of a popular framework for the informing process (the Meerwein model). This study adopted a qualitative approach which was broadly set in an interpretive perspective – focusing on practices, subjective meanings that stakeholders attached to their practices, and the context. Study findings are presented under three main themes. The informational theme describes how site staff reportedly employed numerous strategies to ensure that information presented to potential participants was understandable, such as simplifying, using preferred language, using analogies, using culturally appropriate terms and promoting discussion. The emotional theme describes how site staff implemented several strategies to try respond to emotions of anxiety and to try address feelings of suspicion, such inquiring about and collating suspicions, using trustworthy sources (ex-participants or influential community members) and referring to safe, licensed vaccines. The relational theme describes how site-staff reportedly employed various practices to develop respectful relationships (by creating a friendly environment) that are responsive to cultural norms, such as requesting permission to break cultural norms, and using culturally acceptable terms. The study concludes that strategies employed appear consistent with several key principles of adult learning, and communication, as well as with ethical guideline recommendations for HIV vaccine trials. These findings imply that the individual consent process is best understood as embedded in a larger process of engagement and that consent staff at sites need to have core communicative competencies, need to be sensitive to the emotional aspects of their engagements, and need to be culturally competent. Recommendations are made for key stakeholders such as Research Ethics Committees, CAB members, and ethical guideline developers. Recommendations are made to strengthen the informed consent process for research in resource-limited settings

Operationalising a real-time research ethics approach: supporting ethical mindfulness in agriculture-nutrition-health research in Malawi

BACKGROUND: There have been notable investments in large multi-partner research programmes across the agriculture-nutrition-health (ANH) nexus. These studies often involve human participants and commonly require research ethics review. These ANH studies are complex and can raise ethical issues that need pre-field work, ethical oversight and also need an embedded process that can identify, characterise and manage ethical issues as the research work develops, as such more embedded and dynamic ethics processes are needed. This work builds on notions of 'ethics in practice' by developing an approach to facilitate ethical reflection within large research programmes. This study explores the application of a novel 'real-time research ethics approach' (RTREA) and how this can support ethical mindfulness. This involves embedding ethical analysis and decision-making within research implementation, with a continuous dialogue between participants and researchers. The aim is to improve ethical responsiveness and participant experience, which in turn may ethically support adherence and retention. In this case study, a bioethics team (BT) was embedded in a community-based randomised, controlled trial conducted in rural Malawi, titled the 'Addressing Hidden Hunger with Agronomy'. To identify ethical issues, the researchers conducted ten focus group discussions, fourteen in-depth interviews with key informants, two workshops, observed two sensitisation and three activity meetings conducted by the trial team, and analysed fifteen reports from pre-trial to trial implementation. RESULTS: The RTREA facilitated the identification of social and ethical concerns and made researchers aware of participants' 'lived research experience'. To address concerns and experiences, the BT worked with researchers to facilitate conversation spaces where social and ethical issues were discussed. Conversation spaces were designed to create partnerships and promote participatory methods to capture trial participants' (TPs) perspectives and experiences. CONCLUSIONS: The use of RTREA showed the value of real-time and continuous engagement between TPs and researchers. These real-time processes could be embedded to complement traditional ethical guidance and expert opinions. A deeper engagement appeared to support greater operationalising of principles of inclusion, empowerment, and participant autonomy and supported researchers 'ethical mindfulness' which in turn may support instrumental outcomes of high recruitment, retention, and adherence levels

Preparing for a community-based agriculture-to-nutrition trial in rural Malawi: formative research to assess feasibility and inform design and implementation decisions.

BACKGROUND: This study reports findings from formative research conducted to assess the feasibility and inform the design and implementation of the Addressing Hidden Hunger with Agronomy (AHHA) trial. The AHHA trial was a randomised, controlled trial conducted in rural Malawi, in which participants were given maize flour biofortified with selenium or control flour not biofortified with selenium for a period of 10 weeks, after which blood samples were taken to measure selenium status. METHODS: Formative research was conducted in villages near to the AHHA trial study site 1 year before the planned intervention. A short questionnaire with adult women (n = 50), focus group discussions with male (n groups = 3) and female (n groups = 3) community members, and in-depth key informant interviews (n = 7) were conducted to understand community practices and perceptions. FINDINGS: Meals were typically cooked and eaten at home in this community, while participants reported that maize flour would be less readily sold than maize grain - important considerations for the design of the trial. Regarding intervention delivery, we identified potential concerns around effects on fertility, links between blood sampling and witchcraft, and the potential for social stigma if community members considered participants lazy for receiving free flour. Participants reported that involvement of the Malawi government partners including health extension workers would increase trust. INTERPRETATION: Following the formative research, the AHHA trial appeared feasible. However, community sensitisation would be essential to address potential fears and concerns; effective sensitisation would support recruitment and treatment adherence, and would protect the safety and wellbeing of participants and researchers. People in positions of authority and trust including village headmen, religious leaders, health and agriculture extension workers, and community care groups should be involved in community sensitisation

Can selenium deficiency in Malawi be alleviated through consumption of agro-biofortified maize flour? Study protocol for a randomised, double-blind, controlled trial

Micronutrient deficiencies including selenium (Se) are widespread in Malawi and potentially underlie a substantial disease burden, particularly among poorer and marginalised populations. Concentrations of Se in staple cereal crops can be increased through application of Se fertilisers – a process known as agronomic biofortification (agro-biofortification) – and this may contribute to alleviating deficiencies. The Addressing Hidden Hunger with Agronomy (AHHA) trial aims to establish the efficacy of this approach for improving Se status in rural Malawi

Perspectives of agriculture, nutrition and health researchers regarding research governance in Malawi. Using a leadership, ethics, governance and systems framework

Abstract Background Research ethics is intertwined with and depends on building robust and responsive research governance systems alongside researchers. Globally there has been substantial investment in agriculture, nutrition, and health (ANH) research motivated by the need to improve health outcomes, such as micronutrient deficiencies in Sub-Saharan Africa. Although there has been a notable focus on ethical issues inherent in ANH studies, there has been scanty research examining researchers’ attitudes related to ANH research. This study was conducted to explore the perspectives of researchers who conducted an agronomic biofortification study in Malawi. Methodology In-depth interviews were conducted with a purposive sample of ten ANH researchers. Interviews were conducted online via Zoom, audio-recorded, transcribed verbatim, and thematically analysed using the Leadership, Ethics, Governance and Systems Framework. Results Four core aspects emerged: Leadership: The relevance of building ethics leadership and ethical competence among researchers. Ethics: There is a need to develop a framework that operationalises core ethical values that can guide the implementation of ANH research. Governance: Research guidelines were perceived to be too generic to guide ANH research. Systems: Researchers’ recommended the establishment of a specialised ANH research ethics committee. Conclusions The findings highlight the significance of building ethics leadership and supporting ethical competency amongst researchers. Researchers recommended the development of tailored approaches rather than utilising generic governance systems and frameworks that are drawn from medical research and thus not fit for purpose in this field. In Malawi, specialised ethics review committees are needed to guide ANH research

Examining study participants' decision-making and ethics-related experiences in a dietary community randomized controlled trial in Malawi

BACKGROUND: The participant recruitment process is a key ethical pivot point when conducting robust research. There is a need to continuously review and improve recruitment processes in research trials and to build fair and effective partnerships between researchers and participants as an important core element in ensuring the ethical delivery of high-quality research. When participants make a fair, informed, and voluntary decision to enroll in a study, they agree to fulfill their roles. However, supporting study participants to fulfill study requirements is an important ethical obligation for researchers, yet evidenced as challenging to achieve. This paper reports on participants' motivations to volunteer and remain part of a dietary study conducted in Kasungu District, Malawi. METHODS: We conducted twenty in-depth interviews (with chiefs, religious leaders, trial participants, and health surveillance assistants), five systematic ethnographic observations, and fourteen focus group discussions with trial participants and their partners. Interviews were audio-recorded and transcribed verbatim. We used a grounded theory methodology to analyse data that included coding, detailed memo writing, and data interpretation. FINDINGS: The findings reveal that many participants had concerns during the trial. Thematically, experiences included anxieties, mistrust of researchers, rumours, fears of exploitation, and misconceptions. Anonymous concerns collected from the participants were reported to the trial team which enabled the researchers to appropriately support participants. Despite initial concerns, participants described being supported and expressed motivation to take up their role. CONCLUSION: These findings highlight a diverse map of multiple notions of what is ethically relevant and what can impact participation and retention within a study. The study has revealed how embedding a responsive approach to address participants' concerns and ethical issues can support trust relationships. We argue for the need to employ embedded ethics strategies that enhance informed consent, focus on participants' needs and positive experiences, and support researchers to fulfill their roles. This work highlights the need for research ethics committees to focus on the risks of undue influence and prevent exploitation especially in settings with a high asymmetry in resources and power between researcher and participant groups. TRIAL REGISTRATION: The Addressing Hidden Hunger with Agronomy (Malawi) trial was registered on 5th March 2019 (ISCRTN85899451)

A qualitative study exploring stakeholder perspectives on the use of biological samples for future unspecified research in Malawi

CITATION: Matandika, L., et al. 2020. A qualitative study exploring stakeholder perspectives on the use of biological samples for future unspecified research in Malawi. BMC Medical Ethics, 21:61, doi:10.1186/s12910-020-00503-4.The original publication is available at https://bmcmedethics.biomedcentral.comAbstract : Background: There is growing interest in the collection, storage and reuse of biological samples for future research. Storage and future use of biological samples raise ethical concerns and questions about approaches that safeguard the interests of participants. The situation is further complicated in Africa where there is a general lack of governing ethical frameworks that could guide the research community on appropriate approaches for sample storage and use. Furthermore, there is limited empirical data to guide development of such frameworks. A qualitative study to address this gap was conducted with key stakeholders in Malawi to understand their experiences and perspectives regarding storage and usage of samples for future research. Methods: This study conducted 13 in-depth interviews with ethics committee members, regulators and researchers, and five focus group discussions with community representatives and clinical trial participants in Malawi. Interviews and focus group discussions were audio-recorded, transcribed verbatim, and thematically analysed. Results: On the current regulatory guidelines that governs the collection, storage and reuse of samples in Malawi, participants highlighted their different understanding of it, with some indicating that it prohibited the reuse and sharing of samples, while others believed it permitted. Views on the informed consent model used in Malawi, some stakeholders expressed that the current model limited options for sample contributors regarding future use. Researchers supported storing samples for future use in order to maximize their value and reduce research costs. However, they expressed concern over the exportation of samples highlighting that it could lead to misuse and would not support the development of research capacity within Malawi. They recommended use of broad consent or tiered consent and establishment of biobanks to address these concerns. Conclusions: Study findings highlighted the need for a review of the current regulatory guideline and the development of infrastructure to support the use of stored biological samples for future use among the research community in Malawi. At the moment, there are ethical and practical concerns arising from the collection, storage and secondary use of biological samples make it hard to reconcile scientific progress and the protection of participants.https://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-020-00503-4Publisher's versio

Decolonizing Global Health Research: Perspectives from US and International Global Health Trainees

Background: “Decolonizing global health” (DGH) may help global health trainees understand and remediate the effects of historical colonialism on global health, but little is known regarding how trainees perceive DGH. Understanding their perspectives is critical for designing educational interventions tailored to their needs. Objectives: To understand how trainees perceive DGH research and to determine if perspectives differ between trainees from high- (HICs) versus low- and middle-income countries (LMICs). Methods: An online survey of all 2017–2022 pre-doctoral and post-doctoral trainees (n = 111) and mentors (n = 91) within a multi-university program that supports US and international investigators in one-year mentored global health research. The survey evaluated individuals’ self-reported knowledge and attitudes toward DGH and their perceptions of historical colonialism’s impact on eight aspects of global health. Findings: The response rate to trainee surveys was 56%. Trainees from LMICs were less aware of the concept of DGH; 5/25 (20%) had never heard of DGH and 16/25 (64%) reported that they “know a little,” whereas all HIC trainees had heard of DGH and 29/36 (81%) reported that they “know a little” (p = 0.019). For three aspects of global health (i.e., which research questions get asked; development of collaborative relationships; and data/statistical analyses), trainees from LMICs were more likely to report positive effects of colonialism. However, in open-ended responses, no thematic differences existed between how LMIC and HIC trainees defined DGH (i.e., actively eliminating power imbalances; prioritizing local needs; promoting local leadership; providing equitable opportunities; and ensuring programs are culturally appropriate). Conclusions: Different perspectives surrounding what DGH means suggest a shared understanding may be needed and is arguably prerequisite to designing educational interventions to help global health trainees recognize, understand, and act in global health. Future research is needed to understand perspectives on decolonization across diverse contexts with attention to constructs such as race, ethnicity, and gender

Biofortified Maize Improves Selenium Status of Women and Children in a Rural Community in Malawi: Results of the Addressing Hidden Hunger With Agronomy Randomized Controlled Trial

Background: Selenium deficiency is widespread in the Malawi population. The selenium concentration in maize, the staple food crop of Malawi, can be increased by applying selenium-enriched fertilizers. It is unknown whether this strategy, called agronomic biofortification, is effective at alleviating selenium deficiency. Objectives: The aim of the Addressing Hidden Hunger with Agronomy (AHHA) trial was to determine whether consumption of maize flour, agronomically-biofortified with selenium, affected the serum selenium concentrations of women, and children in a rural community setting. Design: An individually-randomized, double-blind placebo-controlled trial was conducted in rural Malawi. Participants were randomly allocated in a 1:1 ratio to receive either intervention maize flour biofortified with selenium through application of selenium fertilizer, or control maize flour not biofortified with selenium. Participant households received enough flour to meet the typical consumption of all household members (330 g capita−1 day−1) for a period of 8 weeks. Baseline and endline serum selenium concentration (the primary outcome) was measured by inductively coupled plasma mass spectrometry (ICP-MS). Results: One woman of reproductive age (WRA) and one school-aged child (SAC) from each of 180 households were recruited and households were randomized to each group. The baseline demographic and socioeconomic status of participants were well-balanced between arms. No serious adverse events were reported. In the intervention arm, mean (standard deviation) serum selenium concentration increased over the intervention period from 57.6 (17.0) μg L−1 (n = 88) to 107.9 (16.4) μg L−1 (n = 88) among WRA and from 46.4 (14.8) μg L−1 (n = 86) to 97.1 (16.0) μg L−1 (n = 88) among SAC. There was no evidence of change in serum selenium concentration in the control groups. Conclusion: Consumption of maize flour biofortified through application of selenium-enriched fertilizer increased selenium status in this community providing strong proof of principle that agronomic biofortification could be an effective approach to address selenium deficiency in Malawi and similar settings. Clinical Trial Registration: http://www.isrctn.com/ISRCTN85899451, identifier: ISRCTN85899451

Proceedings of the 4th World Conference on Research Integrity

CITATION: O’Brien, S. P., et al. 2016. Proceedings of the 4th World Conference on Research Integrity. Research Integrity and Peer Review, 1:9, doi:10.1186/s41073-016-0012-9.The original publication is available at https://researchintegrityjournal.biomedcentral.comThese Proceedings contain the abstracts of the presentations given at the 4th World Conference in concurrent sessions, partner symposia, and poster sessions. Also included are summaries of the discussions in three focus tracks, which allowed delegates to consider and work on questions about the roles of funders, institutions, and countries in improving research systems and strengthening research integrity. Videos of the plenary presentations are available at the conference website (www.wcri2015.org).https://researchintegrityjournal.biomedcentral.com/articles/10.1186/s41073-016-0012-