M Walker3; J Hamley2; P Milton2; F Monnot1; B Pedrique1; M G Basáñez2;
1 Drugs for Neglected Diseases initiative, Switzerland; 2 Imperial College London, UK; 3 Royal Veterinary College, UK
DiscussionLymphatic filariasis (elephantiasis) and onchocerciasis (river blindness) are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of the adult worms. New drugs or combinations of existing drugs are needed to improve patient therapies in the clinical setting and to enhance the effectiveness of public health interventions in transmission hotspots where elimination is unfeasible by 2020/2025. Several novel therapies and new regimens are currently in pre-clinical and clinical testing. Clinical trial simulators project patient outcomes to assist with the design of clinical trials. They are used in the pharmaceutical sector but have not been widely applied in the NTD domain, where their resource-optimising payoffs could be highly beneficial. Using river blindness as an example, we demonstrate the utility of clinical trial simulation using a novel individual-based onchocerciasis transmission model that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of phase II/III trials, including infection status-based recruitment criteria and follow-up times after treatment for measuring different infection indicators. We discuss how target product profiles must be carefully formulated to ensure they are demonstrable in a clinical trial's framework.