Evaluation of alternative endpoints for ZIKV vaccine efficacy trials.
Evaluation of alternative endpoints for ZIKV vaccine efficacy trials.
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ZIKV 疫苗功效试验替代终点的评估。
DOI：
10.1016/j.vaccine.2019.02.066
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发表时间：
2019
期刊：
影响因子：
5.5
通讯作者：
Bellan,StevenE
中科院分区：
文献类型：
--
作者：
Mercaldo,RachelA;Bellan,StevenE
怀孕期间感染寨卡病毒 (ZIKV) 与小头畸形和其他出生缺陷有关，统称为先天性寨卡综合症 (CZS)。 2015-16 年流行期间，ZIKV 在美洲传播，并迅速加入其他已知致畸病原体 TORCH 的行列。多种 ZIKV 疫苗已被开发用于保护孕妇和育龄妇女。然而，ZIKV 感染发病率此后已大幅下降，不良出生结果也很少见。在这种低发病率时期，在大型 III 期临床试验中研究疫苗对 CZS 的保护功效可能是不可行的。如果试验开始，研究人员可能会采取替代的临床终点。在这项研究中，我们模拟了各种疫苗临床试验场景，以评估 CZS 终点在疫苗研究中的可行性，并将 CZS 与其他潜在结果进行比较：通过每周、每两周或每月测试检测到的 ZIKV 感染以及实验室确认的有症状的寨卡病毒病。我们比较了 80% 统计功效所需的样本量，以检测每种情况下的疫苗功效和试验持续时间。我们的结果表明，CZS 临床终点的可行性取决于季节性流行期间模拟临床试验的时间安排，因为 CZS 风险随感染的三个月而变化。这一结果强调了在设计针对致畸病原体的疫苗功效试验时需要考虑的其他因素。
Zika virus (ZIKV) infection during pregnancy is associated with microcephaly and other birth defects, collectively termed Congenital Zika Syndrome (CZS). During the epidemic in 2015–16, ZIKV spread through the Americas and quickly joined the list of other known teratogenic pathogens, TORCH. Multiple ZIKV vaccines have been developed for protection of pregnant women and women of childbearing age. However, ZIKV infection incidence has since waned substantially, and adverse birth outcomes are rare outcomes of infection. Studying a vaccine’s protective efficacy against CZS in a large phase III clinical trial may be infeasible in such times of low incidence. Should trials be initiated, researchers may resort to alternative clinical endpoints.In this study, we simulate a variety of vaccine clinical trial scenarios to evaluate the feasibility of the CZS endpoint in vaccine studies and compare CZS to other potential outcomes: ZIKV infection detected through weekly, biweekly, or monthly testing and laboratory-confirmed, symptomatic Zika Virus Disease. We compare the sample size required for 80% statistical power to detect vaccine efficacy and trial duration for each scenario. Our results show the feasibility of CZS clinical endpoints depends on the timing of simulated clinical trials in the course of a seasonal epidemic, due to CZS risk varying with trimester of infection. This result highlights additional considerations needed when designing vaccine efficacy trials of protection against teratogenic pathogens.