8th and 9th of October 2019
On 8th and 9th October 2019, the Coalition for Epidemic Preparedness Innovations (CEPI) organised a workshop on “Launching Lassa fever epidemiology studies across West Africa”, with the following objectives:
•Allow the technical working groups (TWGs) and Programme Steering Committee (PSC) to meetface to face, thereby ensuring cohesiveness of the group and open communications beforelaunch of the CEPI-funded Lassa fever epidemiology study
•Review study launch plans and resolve issues that may impede study progress
•Share best practices, experiences, and insights
•Review critical attributes of the study protocol and TWG documents/deliverables
The workshop was held at Noguchi Memorial Institute for Medical Research (NMIMR) in Accra, Ghana.
Gunnstein Norheim, CEPI, opened the workshop and explained the meeting objective: preparing for the launch of Lassa fever epidemiology studies across five West-African countries, with the intention of investigating the incidence as well as seroprevalence of Lassa fever. The studies aim to generate new knowledge about Lassa fever, and to inform future clinical vaccine trials.
Jakob Cramer, CEPI, explained how the epi studies fit into the overall clinical development plan for a Lassa vaccine. In the context of data needs to assess the feasibility of Phase IIb/III clinical trials, he listed the objectives of the epi studies:
1)gaining knowledge of incidence/prevalence in subgroups;
2)assessing risk factors for infection and disease;
3)observing the clinical course and outcomes of disease;
4)assessing the frequency of co-infection with malaria parasites; and
5)capacity building in conducting clinical trials in endemic areas.
Chikwe Ihekweazu, CEO of the Nigeria Centre for Disease Control, placed the epi studies in a public health context. He stated that many unknowns remain about Lassa fever, as well as many challenges including a lack of standardised care, of trained personnel, and of capacity in diagnostics, as well as huge logistics challenges to maintain a supply of samples and reagents. Against this backdrop, he cited the significant import of the Lassa epidemiology studies, which will:
1)Inform the design of a clinical Phase IIb/III randomised, placebo-controlled trial, hopefullybringing us closer to a Lassa fever vaccine;
2)help identify sites suitable for the conduct of clinical trials, so that the next time around we canhit the ground running;
3)enable the strengthening of sites and investigators, and build their capacity to conduct andmanage clinical field trials in the future; and
4)facilitate decisions regarding vaccination strategies.
Vasee Moorthy, head of R&D Blueprint at WHO, reviewed some of the key evidence gaps that were discussed at a September meeting on Lassa vaccine development progress arranged by WHO in Senegal:
1)Whether exposure to Lassa results in lifelong immunity;
2)Need for serology and disease incidence studies to be conducted in endemic areas to characterise risk factors, co-infections, and disease;
3)Understand whether reinfections really occur;
4)Need to address the critical question of lineage-specificity of immunity;
5)Understand the spectrum of disease, i.e., the extent of undiagnosed, mild, and asymptomaticinfection
Dr Moorthy stated that the epidemiology studies offer a major opportunity to build capacity, even for Phase IIb/III studies in the countries involved. It marks the beginning of country engagement in end-to-end product development for an important endemic disease in Africa, with the possibility of vaccine manufacturing in Europe or North America. He underscored the need for linking scientific knowledge and public health as well as regulatory and ethical considerations with clinical development, and advocated for thoughtful collaboration between partners in West Africa and high-income countries.
Each of the five study countries then presented on their specific projects, giving a background of Lassa fever in their context, existing and planned research, treatment and public health efforts, and progress toward execution of the Lassa epi study. Presenters included study coordinators and principal investigators from each site. Across all countries, priority activities centered on reaching final contract agreements and preparing the necessary documents for ethics review submission (protocol, case report forms, informed consent/assent forms, etc.).
CEPI staff provided an overview of financial and project management best practices, sharing information on processes for funds disbursement and activity reporting, and reviewing a framework for project management and communications to be coordinated both locally within country consortia as well as centrally with oversight by CEPI.
Each of the Technical Working Groups for the project met during breakout sessions held in the afternoon of the 8th and morning of the 9th. (The Programme Steering Committee held a closed launch meeting in parallel.) The Field Implementation TWG discussed key considerations around finalising the core protocol and other documents necessary for ethical review. The Laboratory TWG reviewed the study flow diagram, sampling procedures, and discussed the steps needed to develop and finalise the necessary protocols and guidelines for laboratory activities. The Data Management & Statistical Analysis TWG focused on identifying requirements for a common data management platform and identified steps and timelines to development, testing, deployment and use. The Capacity Strengthening TWG reviewed a list of trainings envisioned for the study, soliciting feedback and consensus on the format and priority of trainings to be conducted. The Communications and Community Engagement TWG discussed priorities for ensuring robust local engagement, including a stakeholder analysis, use of existing community health workers, and developing tools for rapid communications to subjects as well as local, regional, and national stakeholders.
Peter Smith with the London School of Hygiene and Tropical Medicine offered insights on the collaborative execution of field trials such as the Lassa epi studies, offering as a reference the book Field trials of health interventions – A toolbox. He shared information about the INDEPTH Network as an example of existing resources for standardised tools for surveillance activities. Dr Smith further shared that CEPI and EDCTP have decided to partner on a joint call for proposals (CFP) for phase II/III clinical trials of LASV vaccine candidates, with a call budget of € 40 million and a deadline for applications of April 7, 2020. The scope of the call is to prepare and conduct one or more large-scale clinical trial(s) with the potential to achieve proof-of-concept and/or demonstration of efficacy for candidate vaccines against LASV.
Professor Abraham Annan, director of the Noguchi Memorial Research Institute hosting the workshop, offered a welcome to participants and underscored the importance of the workgroup’s mission to global health security. He shared his enthusiasm for future engagements with the Lassa project participants in supporting preparedness for, and prevention of, infectious diseases in the region. Nicole Lurie (CEPI) and Tom Verstraeten (P-95) chaired a final open discussion segment. During this segment, participants discussed clinical care procedures and support for management of identified Lassa cases, policies for sharing of study data between CEPI and country partners, EDCTP application guidance, and next steps for resolving questions concerning the core protocol and other documents raised during the TWG and other discussions. Jakob Cramer closed with a few remarks on launch timeline and next steps, including final study protocol refinements and other needs for ethical review. The meeting was then adjourned and participants thanked for their attendance and valuable contributions.