'It looks like you just want them when things get rough': civil society perspectives on negative trial results and stakeholder engagement in HIV prevention trials.

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the global HIV epidemic, CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders in HIV research. This study explored the perspectives of CSO representatives involved in HIV prevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents from South African and international CSOs representing activist and advocacy groups, community mobilisation initiatives, and human and legal rights groups were purposively sampled based on involvement in HPTs. Interviews were conducted from February-May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively. CSO representatives largely described positive outcomes of recent microbicide and HIV vaccine trial terminations, particularly in South Africa, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time-points, as well as the need for legitimate alternatives to CABs as mechanisms for engagement. Key issues for CSOs in relation to research were also raised.

Civil society perspectives on negative biomedical HIV prevention trial results and implications for future trials.

Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building.

Convergent ethical issues in HIV/AIDS, tuberculosis and malaria vaccine trials in Africa: Report from the WHO/UNAIDS African AIDS Vaccine Programme's Ethics, Law and Human Rights Collaborating Centre consultation, 10-11 February 2009, Durban, South Africa.

BACKGROUND: Africa continues to bear a disproportionate share of the global HIV/AIDS, tuberculosis (TB) and malaria burden. The development and distribution of safe, effective and affordable vaccines is critical to reduce these epidemics. However, conducting HIV/AIDS, TB, and/or malaria vaccine trials simultaneously in developing countries, or in populations affected by all three diseases, is likely to result in numerous ethical challenges. METHODS: In order to explore convergent ethical issues in HIV/AIDS, TB and malaria vaccine trials in Africa, the Ethics, Law and Human Rights Collaborating Centre of the WHO/UNAIDS African AIDS Vaccine Programme hosted a consultation on the Convergent Ethical Issues in HIV/AIDS, TB and Malaria Vaccine Trials in Africa in Durban, South Africa on the 10-11 February 2009. RESULTS: Key cross cutting ethical issues were prioritized during the consultation as community engagement; ancillary care obligations; care and treatment; informed consent; and resource sharing. CONCLUSION: The consultation revealed that while there have been few attempts to find convergence on ethical issues between HIV/AIDS, TB and malaria vaccine trial fields to date, there is much common ground and scope for convergence work between stakeholders in the three fields.

Stakeholder perspectives on ethical challenges in HIV vaccine trials in South Africa.

There is little published literature on the ethical concerns of stakeholders in HIV vaccine trials. This study explored the ethical challenges identified by various stakeholders, through an open-ended, in-depth approach. While the few previous studies have been largely quantitative, respondents in this study had the opportunity to spontaneously identify the issues that they perceived to be of priority concern in the South African context. Stakeholders spontaneously identified the following as ethical priorities: informed consent, social harms, collaborative relationships between research stakeholders, the participation of children and adolescents, access to treatment for participants who become infected with HIV, physical harms, fair participant and community selection, confidentiality, benefits, and payment. While there is some speculation that research in developing countries poses special ethical challenges, overall no issues were identified that have not been anticipated in international guidance, literature and popular frameworks. However, the South African context affords a distinctive gloss to these expected issues; for example, respondents were concerned that the predominant selection of black participants may perpetuate racist practices of apartheid. Stakeholders should be aware of contextual factors impacting on the implementation of ethical principles. We make a series of recommendations for South African trials, including amendments to the ethical-legal framework and research policies, and, for further research.

The 'over-researched community': An ethics analysis of stakeholder views at two South African HIV prevention research sites.

Health research in resource-limited, multi-cultural contexts raises complex ethical concerns. The term 'over-researched community' (ORC) has been raised as an ethical concern and potential barrier to community participation in research. However, the term lacks conceptual clarity and is absent from established ethics guidelines and academic literature. In light of the concern being raised in relation to research in low- and middle-income countries (LMICs), a critical and empirical exploration of the meaning of ORC was undertaken. Guided by Emanuel et al.'s (2004) eight principles for ethically sound research in LMICs, this study examines the relevance and meaning of the terms 'over-research' and 'over-researched community' through an analysis of key stakeholder perspectives at two South African research sites. Data were collected between August 2007 and October 2008. 'Over-research' was found to represent a conglomeration of ethical concerns often used as a proxy for standard research ethics concepts. 'Over-research' seemed fundamentally linked to disparate positions and perspectives between different stakeholders in the research interaction, arising from challenges in inter-stakeholder relationships. 'Over-research' might be interpreted to mean exploitation. However, exploitation itself could mean different things. Using the term may lead to obscured understanding of real or perceived ethical concerns, making it difficult to identify and address the underlying concerns. It is recommended that the term be carefully and critically interrogated for clarity when used in research ethics discourse. Because it represents other legitimate concerns, it should not be dismissed without careful exploration.

Towards a Science of Community Stakeholder Engagement in Biomedical HIV Prevention Trials: An Embedded Four-Country Case Study.

OBJECTIVES: Broad international guidelines and studies in the context of individual clinical trials highlight the centrality of community stakeholder engagement in conducting ethically rigorous HIV prevention trials. We explored and identified challenges and facilitators for community stakeholder engagement in biomedical HIV prevention trials in diverse global settings. Our aim was to assess and deepen the empirical foundation for priorities included in the GPP guidelines and to highlight challenges in implementation that may merit further attention in subsequent GPP iterations. METHODS: From 2008-2012 we conducted an embedded, multiple case study centered in Thailand, India, South Africa and Canada. We conducted in-depth interviews and focus groups with respondents from different trial-related subsystems: civil society organization representatives, community advocates, service providers, clinical trialists/researchers, former trial participants, and key HIV risk populations. Interviews/focus groups were recorded, and coded using thematic content analysis. After intra-case analyses, we conducted cross-case analysis to contrast and synthesize themes and sub-themes across cases. Lastly, we applied the case study findings to explore and assess UNAIDS/AVAC GPP guidelines and the GPP Blueprint for Stakeholder Engagement. RESULTS: Across settings, we identified three cross-cutting themes as essential to community stakeholder engagement: trial literacy, including lexicon challenges and misconceptions that imperil sound communication; mistrust due to historical exploitation; and participatory processes: engaging early; considering the breadth of "community"; and, developing appropriate stakeholder roles. Site-specific challenges arose in resource-limited settings and settings where trials were halted. CONCLUSIONS: This multiple case study revealed common themes underlying community stakeholder engagement across four country settings that largely mirror GPP goals and the GPP Blueprint, as well as highlighting challenges in the implementation of important guidelines. GPP guidance documents could be strengthened through greater focus on: identifying and addressing the community-specific roots of mistrust and its impact on trial literacy activities; achieving and evaluating representativeness in community stakeholder groups; and addressing the impact of power and funding streams on meaningful engagement and independent decision-making.

HIV prevention responsibilities in HIV vaccine trials: complexities facing South African researchers.

Researchers should protect the welfare of research participants through providing methods to reduce their risk of acquiring HIV. This is especially important given that late-phase HIV vaccine trials enrol HIV-uninfected trial volunteers from high-risk populations. Current ethical guidelines may be difficult for stakeholders to implement, and we know very little about what prevention services researchers are currently providing to participants or their successes, best practices and challenges. We recommend that current normative guidance be systematically reviewed and actual practice at vaccine sites be documented. Adding new tools to the current package of prevention services will involve complex decision making with few set standards, and regulatory and scientific challenges. We recommend that stakeholders (including regulators) convene to consider standards of evidence for new tools, and that decision-making processes be explicitly documented and researched. A further critical ethical task is exploring the threshold at which adding new tools will compromise the validity of trial results.