The East African Community (EAC) has experienced significant increase in volume and complexity of clinical research driven by epidemics of emerging and remerging infectious diseases such as HIV, Ebola and COVID-19, requiring expertise in scientific and ethical review and conduct of research and a robust and pragmatic research regulatory framework. The overall goal is to strengthen scientific and ethics capacity in EAC for high quality research review, conduct and oversight, at international standards. The specific objectives are: 1. To train NRRA personnel, REC members, researchers and clinicians on scientific and ethics review and conduct of research with emerging and complex study designs including adaptive platform trials 2. To train NRRA personnel and REC members on oversight, monitoring and pharmacovigilance of clinical trials and 3. To train NRRA personnel, REC and research administrators on personal effectiveness and leadership skills (PELS) to manage the increasingly complex research processes. Methods: We will implement this project within a consortium of research scientists from the six partner states collaborating with the EU partner, with the East African Health Research Commission as the strong nucleus for coordination and dissemination of results. The project will be hosted at the Infectious Diseases Institute (IDI), where within a previous NIH funded program (5G11 TW011309-01) we built capacity for REC members, researchers and REC administrators for 7 RECs in Uganda, with significant improvement in knowledge, PELS, quality and turnaround time of research review and researcher satisfaction. This proposal fits within the scope of GH-EDCTP3-2022-01-05 call, whose aim is to strengthen clinical research capacity and improve efficiency of the regulatory environment for effective development, delivery and uptake of new and improved safe health technologies and rapid response to emerging epidemics guaranteeing international standards and attainment of SDG3.

Evidence of the impact of long-acting spatial repellents (LASR) on malaria burden is urgently needed. We propose to conduct a rigorous, cluster-randomised trial to evaluate the effectiveness of LASR and indoor residual spraying (IRS) in Kenya. The trial will include 66 clusters (villages) in western Kenya where malaria transmission is intense. The clusters will be randomised to one of three study arms including: (1) LASR (intervention #1) with SC Johnson’s Guardian™ product, (2) IRS with pirimiphos-methyl (intervention #2), and (3) standard control (no intervention). All clusters will receive standard malaria control interventions, including long-lasting insecticidal nets (LLINs) distributed by the Kenyan National Malaria Control Program and malaria vaccines (as and when these are deployed). The evaluation will include repeated cross-sectional community surveys (conducted at baseline and then every 6 months for 2 years) to gather information on household characteristics and parasite prevalence in children aged 2-10 years, malaria incidence as captured through health facility surveillance, entomological surveillance, mosquito behaviour studies and insecticide resistance monitoring, qualitative research to explore barriers to delivering LASR and IRS, and an economic evaluation. The primary objective of the study is to evaluate the impact of LASR (Guardian™) as compared to standard control on parasite prevalence in western Kenya. We will test the hypothesis that parasite prevalence as measured in cross-sectional surveys will be lower in intervention clusters (villages randomised to receive LASR), than in control clusters (villages randomised to standard control). The field work in Kenya will be led by the Kenya Medical Research Institute (KEMRI), coordinated by the Liverpool School of Tropical Medicine (LSTM), and supported by Radboud University Medical Centre, Netherlands, the Institute of Tropical Medicine, Belgium, and the US Centers of Disease Control.

The increased number of Clinical Trials taking place in Africa as well as the complexity of Clinical Trials designs require that the countries have the regulatory capacity to review, monitor and utilize data generated from the research. Research Ethics Committees/Institutional Review Boards, Institutional Animal Care and Use Committees and National Regulatory Agencies (NRAs) are required to be abreast with the evolving landscape thus require continuous capacity building as well as have platforms to share Clinical Trials information with both the public and private sector. The 11th Annual National Research Ethics Conference held in 2021 in Uganda highlighted challenges in the low and middle income countries for research ethics and open science specifically, the lack of infrastructure for open data sharing and fair data management. Specifically, i) lack of the national and regional guidelines and codes of conduct for scientific integrity ii) limited training and education in responsible conduct of research and pharmacovigilance. This proposal focuses on strengthening ethics and responsible conduct of Clinical Trials in East and Sub-Saharan Africa project through the establishment of a research ethics and integrity framework, open data access framework for Clinical Trials, E-learning platform for the Good Research Regulatory Research Practice Course and establishing Research Ethics Committees in National Regional Hospitals. The consortium will leverage on the legal establishment of the institutions, collaborative efforts with the partner institutions, East African Health Research Commission (EAHRC), African Vaccine Regulatory Forum (AVAREF). Having a robust regulatory system, encompassing research integrity and open science will ensure that Clinical Trials is conducted to the highest ethical standards and in compliance with existing polices and laws, hence protection of safety, rights and welfare of the individual participants, community, researcher and sponsors.