Designing antifilarial drug trials using clinical trial simulators

Walker, M; Hamley, J; Milton, P; Monnot, F; Pedrique, B; Basáñez, M

Abstract

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.

Citation

Walker, M., Hamley, J., Milton, P., Monnot, F., Pedrique, B., & Basáñez, M. (2020). Designing antifilarial drug trials using clinical trial simulators. Nature Communications, 11(1), https://doi.org/10.1038/s41467-020-16442-y

• Journal Article Type: Article
• Acceptance Date: May 3, 2020
• Publication Date: Jun 1, 2020
• Deposit Date: Jun 16, 2020
• Publicly Available Date: Jun 16, 2020
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 1
• DOI: https://doi.org/10.1038/s41467-020-16442-y
• Public URL: https://rvc-repository.worktribe.com/output/1377183
• Publisher URL: https://doi.org/10.1038/s41467-020-16442-y