Measuring indirect transmission-reducing effects in tuberculosis vaccine efficacy trials: why and how?
Measuring indirect transmission-reducing effects in tuberculosis vaccine efficacy trials: why and how?
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DOI：
10.1016/s2666-5247(23)00112-x
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发表时间：
2023-08
期刊：
影响因子：
38.2
通讯作者：
Garcia-Basteiro, Alberto L.
中科院分区：
文献类型：
--
作者：
Nelson, Kristin N.;Churchyard, Gavin;Cobelens, Frank;Hanekom, Willem A.;Hill, Philip C.;Lopman, Benjamin;Mave, Vidya;Rangaka, Molebogeng X.;Vekemans, Johan;White, Richard G.;Wong, Emily B.;Martinez, Leonardo;Garcia-Basteiro, Alberto L.
结核病是全球主要的细菌性死因。2021年，有1060万人出现症状性结核病，160万人死亡。七种有希望的候选疫苗旨在预防青少年和成人结核病，目前正处于后期临床试验阶段。传统的3期试验提供了关于接种疫苗的个体对感染或疾病的直接保护的信息，但它们几乎没有告诉我们可能的间接（即减少传播）效应，这些效应为未接种疫苗的个体提供了保护。因此，拟议的3期试验设计将不会提供关于引入疫苗计划的总体效果的关键信息。关于潜在间接影响的信息对于决策者决定是否以及如何将结核病疫苗引入免疫规划至关重要。我们描述了在关键性试验中测量结核病候选疫苗的间接效应和直接效应的基本原理，并列出了将其测量纳入3期试验设计的几种选择。
Tuberculosis is the leading bacterial cause of death globally. In 2021, 10·6 million people developed symptomatic tuberculosis and 1·6 million died. Seven promising vaccine candidates that aim to prevent tuberculosis disease in adolescents and adults are currently in late-stage clinical trials. Conventional phase 3 trials provide information on the direct protection conferred against infection or disease in vaccinated individuals, but they tell us little about possible indirect (ie, transmission-reducing) effects that afford protection to unvaccinated individuals. As a result, proposed phase 3 trial designs will not provide key information about the overall effect of introducing a vaccine programme. Information on the potential for indirect effects can be crucial for policy makers deciding whether and how to introduce tuberculosis vaccines into immunisation programmes. We describe the rationale for measuring indirect effects, in addition to direct effects, of tuberculosis vaccine candidates in pivotal trials and lay out several options for incorporating their measurement into phase 3 trial designs.