Stakeholders' engagement with Ebola therapy research in resource limited settings.

BACKGROUND: The current Ebola Virus Disease (EVD) outbreak in West Africa is the largest in history. As of February 18(th) 2015, 23,258 cases of EVD have been cumulatively reported from Nigeria, Senegal, Guinea, Liberia, Mali, Sierra Leone, Spain, the United Kingdom and the United States of America resulting in more than 9,000 deaths. It is therefore exigent to develop prevention and treatment therapies for EVD. DISCUSSION: Several new EVD treatments are in clinical development at this time. Based on lessons learned, four critical processes need to be implemented before clinical trials begin. First, all global EVD research need to be coordinated to promote data sharing and synergistic overlap, while reducing unnecessary duplication of efforts. The World Health Organization is well-placed to undertake such an endeavor. Second, governments of affected nations where trials are being proposed need to lead discussions regarding immediate access to any proven medications for epidemics. Also, governments need to leverage international resources to support and expand existing national expertise to jointly conduct high-caliber clinical research; and resources must be used to enhance local technical skills and expand existing personnel. Third, ethics committees must review protocols, monitor the research process, and work closely with research scientists to insure the ethical integrity of research throughout the trials. Fourth, community advisory boards (CAB) need to be formed, linked with existing community leadership structures and organized in conjunction with trial implementation. These community structures should work together with ethics committees to facilitate the study design, informed consent process, and study implementation. We must facilitate communication and mutual understanding between trial communities and research teams, and promote positive collaborations between all stakeholders engaged in EVD research. The community engagement process for EVD research is crucial to address myths and misconceptions, and to promote study volunteers' understanding of the research details. The collaboration between all stakeholders is crucial for continued long term partnership to address EVD outbreak and none of the stakeholders should be left behind in ongoing efforts to develop EVD therapies.

Towards achieving transnational research partnership equity: lessons from implementing adaptive platform trials in low- and middle-income countries.

Background: Use of adaptive clinical trials, particularly adaptive platform trials, has grown exponentially in response to the coronavirus disease (COVID-19) pandemic. Implementation of these trials in low- and middle-income countries (LMICs) has been fostered through the formation or modification of transnational research partnerships, typically between research groups from LMICs and high-income countries (HICs). While these partnerships are important to promote collaboration and overcome the structural and economic disadvantages faced by LMIC health researchers, it is critical to focus attention on the multiple dimensions of partnership equity. Methods: Based on informal literature reviews and a meeting with leaders of one of the multinational COVID-19 adaptive platform trials, we describe some important considerations about research partnership equity in this context. Results: We organize these considerations into eight thematic categories: 1) epistemic structures, 2) funding, 3) ethics oversight, 4) regulatory oversight, 5) leadership, 6) post-trial access to interventions, data, and specimens, 7) knowledge translation and dissemination, and 8) research capacity strengthening and maintenance. Within each category we review normative claims that support its relevance to research partnership equity followed by discussion of how adaptive platform trials highlight new dimensions, considerations, or challenges. Conclusion: In aggregate, these observations provide insight into procedural and substantive equity-building measures within transnational global health research partnerships more broadly.

Strategy management in collaborative clinical research partnerships.

PURPOSE: Today's clinical trial partnerships frequently join multi-disciplinary investigators and stakeholders, from different countries and cultures, to conduct research with a broad array of goals. This diversity, while a strength, can also foster divergent views about priorities and what constitutes success, thereby posing challenges for management, operations, and evaluation. As a sponsor and partner in such collaborations, we seek to assist and support their development and implementation of sound research strategies, to optimize their efficiency, sustainability, and public health impact. This report describes our efforts using an adaptation of the well-established Kaplan-Norton strategy management paradigm, in our clinical trials setting. We share findings from our first test of the utility and acceptance of this approach for evaluating and managing research strategies in a collaborative clinical research partnership. RESULTS: Findings from pilot studies and our first implementation in an ongoing clinical research partnership in Liberia, provide initial support for our hypothesis that an adapted version of the Kaplan-Norton strategy management model can have use in this setting. With leadership from within the partnership, analysis artifacts were gathered, and assessments made using standardized tools. Practical feasibility, resonance of the findings with partners, and convergence with other empirical assessments lend initial support for the view that this approach holds promise for obtaining meaningful, useable results for assessing and improving clinical research management. CONCLUSIONS AND IMPLICATIONS: Engaged leadership, thoughtful timing to align with partnership planning cycles, support for the process, and an eye towards the collaboration's long-term goals appear important for developing model understanding and practice. Skepticism about evaluations, and unease at exposing weaknesses, may hinder the effort. Acceptance of findings and associated opportunities for improvement by group leadership, support a growing sense of validity. Next steps aim to test the approach in other partnerships, streamline the methodology for greater ease of use, and seek possible correlations of strategy management assessments with performance evaluation. There is hardly a better example than the COVID-19 pandemic, to spotlight the need for efficient and effective clinical research partnerships to address global health challenges. While heartened by the collaborative spirit driving the effort so far, we cannot let our enthusiasm lull us into thinking that nobility of purpose or an abundance of good will is sufficient. Careful monitoring and adjustment of clinical research strategy in response to changes (e.g., demographics, pathogen evolution, research acceptance, political and cultural environments) are vital to making the needed adjustments that can guide these programs toward successful outcomes. We hope that our work can raise awareness about the importance, relevance, and feasibility of sound strategy management in clinical research partnerships, especially during this time when there is so much at stake.

Preliminary Impacts of an HIV-Prevention Program Targeting Out-of-School Youth in Postconflict Liberia.

Adolescents in Sub-Saharan Africa account for greater HIV/STI (human immuno defiency virus/sexually transmitted infection) burdens and difficult-to-reach populations. This study implemented a community-based HIV/STI program to reach at-risk youth aged 15 to 17 years in postconflict Liberia. Using a randomized controlled trial, community youths were assigned to an adapted version of an effective HIV/STI program, Making Proud Choices, or attention-matched comparison curriculum, General Health Program. Both programs were of similar doses, reach and coverage, and administered in classroom settings by trained health educators. The findings suggest that the adapted HIV/STI program had positive effects on knowledge, sexual refusal and condom use self-efficacy, condom negotiation self-efficacy, positive condom attitudes, parental communication about sex, and negative condom attitudes over time. Culturally adapted community-based, behavioral-driven programs can positively affect mediators of sexual behaviors in at-risk adolescents in postconflict settings. This is the first published report of an evidence-based HIV/STI program on sexual risk-taking behaviors of community youths in Liberia.

Conventional Wisdom versus Actual Outcomes: Challenges in the Conduct of an Ebola Vaccine Trial in Liberia during the International Public Health Emergency.

Clinical trials are challenging endeavors. Planning and implementing an investigational vaccine trial in Liberia, in the midst of an Ebola virus disease (EVD) epidemic that World Health Organization classified a public health emergency of international concern, presented extraordinary challenges. Normally, years of preparation and a litany of tasks lay the groundwork for a successful, randomized, blinded, placebo-controlled trial focused on safety and efficacy. Difficult research settings, unpredictable events, and other unique circumstances can add complexity. The setting in Liberia was especially problematic due to an infrastructure still badly damaged following a lengthy civil war and a very fragile health-care system that was further devastated by the EVD outbreak. The Partnership for Research on Vaccines in Liberia I EVD vaccine trial was planned and implemented in less than 3 months by a Liberian and U.S. research partnership, and its Phase II substudy was fully enrolled 3 months later. Contrasting conventional wisdom with trial outcomes offers an opportunity to compare early assumptions, barriers encountered, and adaptive strategies used, with end results. Understanding what was learned can inform future trial responses when disease outbreaks, especially in resource-poor locations with minimal infrastructure, pose a significant threat to public health.

Impact of school-based HIV prevention program in post-conflict Liberia.

This paper presents findings of a feasibility study to adapt and evaluate the impact of an evidence-based HIV prevention intervention on sexual risk behaviors of in-school 6th grade youth in post-conflict Liberia (n = 812). The study used an attention-matched, group randomized controlled trial. Four matched pairs of elementary/middle schools in Monrovia, Liberia, were randomly assigned to either an adapted eight-module HIV prevention or a general health curriculum. Three- and nine-month impacts of the intervention on sexual risk behaviors and on mediating variables are presented. The intervention significantly impacted protective peer norms and positive condom attitudes and increased frequency of condom use at the nine-month follow-up. The intervention did not impact sexual initiation or multiple sex partnerships. Future intervention research should address the salient pressures that are unique to post-conflict settings and include longer follow-up time periods and smaller class sizes to meaningfully impact sexual initiation and multiple sex partnerships.