Rethinking Clinical Trial Design to Accelerate Therapeutics for Arboviral Epidemics.

Arboviral diseases represent an escalating global health threat, yet therapeutic development has been markedly slower than for other viral illnesses. Key barriers include the unpredictability and variability of arbovirus transmission, which complicate site selection, limit recruitment, and increase delays and the risk of inconclusive trials. Additional challenges include maintaining trial-ready sites, recruitment within the narrow therapeutic window, ensuring rapid diagnostics, and including high-risk groups. To address these barriers, we propose several innovative strategies based on a Clinical Experts meeting convened by the Dengue Alliance. These include pre-activated trial networks for rapid initiation during outbreaks; early-warning surveillance to guide geographic activation using real-time transmission signals; decentralized trial models to expand recruitment beyond major research centers; platform trial designs that allow treatment arms to be added or discontinued adaptively; and participant inclusion based on clinical syndrome supported by rapid diagnostics. Their successful adoption requires regulatory harmonization, ethical oversight, and emphasis on equity.