Preparing for and executing a randomised controlled trial of podoconiosis treatment in Northern Ethiopia: the utility of rapid ethical assessment

Background Community-based randomized controlled trials are often complex pieces of research with significant challenges around the approach to the community, information provision, and decision-making, all of which are fundamental to the informed consent process. We conducted a rapid ethical assessment to guide the preparation for and conduct of a randomized controlled trial of podoconiosis treatment in northern Ethiopia. Methods A qualitative study was carried out in Aneded woreda, East Gojjam Zone, Amhara Regional State from August to September, 2013. A total of 14 In-depth Interviews (IDIs) with researchers, experts, and leaders, and 8 Focus Group Discussions (FGDs) involving 80 participants (people of both gender, with and without podoconiosis), were conducted. Interviews were carried out in Amharic. Data analysis was started alongside collection. Final data analysis used a thematic approach based on themes identified a priori and those that emerged during the analysis. Results Respondents made a range of specific suggestions, including that sensitisation meetings were called by woreda or kebele leaders or the police; that Health Extension Workers were asked to accompany the research team to patients’ houses; that detailed trial information was explained by someone with deep local knowledge; that analogies from agriculture and local social organisations be used to explain randomisation; that participants in the ‘delayed’ intervention arm be given small incentives to continue in the trial; and that key community members be asked to quell rumours arising in the course of the trial. Conclusion Many of these recommendations were incorporated into the preparatory phases of the trial, or were used during the course of the trial itself. This demonstrates the utility of rapid ethical assessment preceding a complex piece of research in a relatively research-naive setting

A phase II, randomised clinical trial to demonstrate the non-inferiority of low-dose MF59®-adjuvanted pre-pandemic A/H5N1 influenza vaccine in adult and elderly subjects

ackground. Effective planning and preparedness against a possi- ble future A/H5N1 influenza pandemic is a major global challenge. Because dose sparing strategies are required to meet the global demand for vaccine, efforts have focused on the development of adju- vanted vaccine formulations of relatively lower antigen content. Aim. This study aimed to demonstrate the non-inferiority of a low-antigen-dose (3.75 mg) A/H5N1 pre-pandemic vaccine com- pared with a licensed, higher-dose (7.5 mg) formulation in adult and elderly subjects. Immunogenicity was assessed according to European and U.S. licensure criteria. Methods. A total of 722 subjects were randomized in equal num- bers to receive either the licensed or low-dose formulation. All subjects received two vaccine doses administered three weeks apart. Immunogenicity was assessed three weeks after the admin- istration of each vaccine dose by hemagglutination inhibition HI), single radial haemolysis (SRH) and microneutralization assays (MN). Local and systemic reactions were assessed over a seven day period post-vaccination. Adverse events were recorded throughout. Results. The low-dose vaccine was demonstrated to be non-infe- rior to the licensed formulation in terms of antibody titres against the vaccine strain. All three European licensure criteria were met by adult subjects in response to the low-dose vaccine; two crite- ria were met by the elderly age group. Cross-reactive antibodies were detected against the heterologous A/H5N1 antigen strains A/Indonesia/05/05 and A/turkeyTurkey/01/05. Both vaccines were generally well tolerated by both age groups. Conclusion. These data demonstrate that a low antigen dose in combination with MF59® adjuvant is adequate for the routine pre-pandemic immunization of adult and elderly subjects