London Centre for Neglected Tropical Disease Research, Department of Pathobiology and Population Sciences, Royal Veterinary College, University of London, Hertfordshire, AL9 7TA, UK.
London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, Imperial College London, London, W2 1PG, UK.
Nat Commun. 2020 Jun 1;11(1):2685. doi: 10.1038/s41467-020-16442-y.
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.
淋巴丝虫病和盘尾丝虫病是被忽视的热带病（NTDs），目标是通过大规模（抗丝虫）药物治疗来消除。这些药物主要对成虫的微丝蚴后代有效。需要新的药物或组合来改善患者治疗，并提高在持续传播热点地区干预措施的效果。目前有几种疗法和方案正在（临床前）测试中。临床试验模拟器（CTSs）预测患者的结果，为临床试验的设计提供信息，但尚未广泛应用于 NTDs，在这些疾病中，它们节省资源的回报可能非常有益。我们使用基于个体的盘尾丝虫病传播模型（EPIONCHO-IBM）来证明 CTSs 的实用性，该模型可以预测一种假设的杀微丝蚴药物的临床试验结果。我们确定了影响临床试验效力的关键设计决策，包括参与者的资格标准和用于测量感染指标的治疗后随访时间。我们讨论了 CTSs 如何帮助提供目标产品概况。
