An empirical study of standards of prevention in South African HIV vaccine trials: Norms, perspectives and practices.

Abstract

and sponsors are required to help HIV vaccine trial participants remain HIVuninfected by ensuring access to HIV risk-reduction interventions, termed the standard of prevention. Ethics guidelines for biomedical HIV prevention trials make a range of recommendations on the standard of prevention, including that participants should be provided with ‘state-of-the-art’ prevention interventions; what should be declared in protocols and informed consent documents; and about how decisions should be made. Recommendations in these guidelines have been intensely debated, and argued to be infeasible and impractical. This qualitative study aimed to identify standard of prevention decision-making and implementation practices at five South African trial sites, explore whether practices meet guideline recommendations, and discuss implications for practices and ethics guidelines. Stakeholders’ perspectives on key recommendations in ethics guidelines were also explored. Practices were examined through a review of site documents and interviews with key research stakeholders. Despite concerns in the literature that guidelines establish ideals that cannot be achieved in practice, this study found high concordance between practices and guideline recommendations. In some instances, site practices exceeded recommendations in guidelines. Practices deviated most from guidelines with regard to ‘negotiating’ standards of prevention packages, the description of prevention plans in protocols and informed consent forms, and the ethical review of monitoring plans. The ‘state-of-the-art’ recommendation was argued as being ‘in the eye of the beholder’ and considered too vague, too absolute and as requiring localisation. The requirement for stakeholder consultation on the evolving standard of prevention was also questioned in terms of who would constitute relevant stakeholders, the difficulties with achieving consensus, and the nature of the consultation process. Stakeholders endorsed ethics requirements that new tools be added to the prevention package when they are scientifically validated and approved by regulatory authorities. In addition, they argued that public health sector availability of the intervention and the phase of the trial also be considered. Funding restrictions, power inequalities, provider promotion of interventions and cultural dynamics, among other complexities were identified as influencing standards of prevention decision-making and/or implementation. Recommendations are made for strengthened practices and improvements to guidelines so that they address empirically identified complexities.