Designing antifilarial drug trials using clinical trial simulators.
Designing antifilarial drug trials using clinical trial simulators.
复制标题
使用临床试验模拟器设计抗丝虫药物试验。
DOI：
10.1038/s41467-020-16442-y
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发表时间：
2020
影响因子：
16.6
通讯作者：
Walker M
中科院分区：
文献类型：
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作者：
Walker M
淋巴丝虫病和盘尾丝虫病是被忽视的热带病 (NTD)，旨在通过大规模（抗丝虫）药物施用来消除。这些药物主要对成虫的微丝蚴后代有活性。需要新的药物或组合来改善患者治疗并提高对持续传播热点的干预措施的有效性。几种疗法和方案目前正在进行临床（前）测试。临床试验模拟器 (CTS) 可以预测患者的治疗结果，为临床试验的设计提供信息，但尚未广泛应用于被忽视的热带疾病，因为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) 展示了 CTS 的实用性，该模型预测了一种假设的杀丝虫药物的试验结果。我们确定影响临床试验功效的关键设计决策，包括参与者资格标准和测量感染指标的治疗后随访时间。我们讨论 CTS 如何帮助了解目标产品概况。
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.