Competing Effects of Indirect Protection and Clustering on the Power of Cluster-Randomized Controlled Vaccine Trials
Competing Effects of Indirect Protection and Clustering on the Power of Cluster-Randomized Controlled Vaccine Trials
复制标题
DOI：
10.1093/aje/kwy047
复制
发表时间：
2018-08-01
影响因子：
5
通讯作者：
Bellan, Steven E.
中科院分区：
文献类型：
--
作者：
Hitchings, Matt D. T.;Lipsitch, Marc;Bellan, Steven E.
评价抗传染病疫苗的试验的效力考虑因疫苗接种的间接保护作用而变得复杂。虽然群集随机对照试验（cRCT）在统计学上不如单独随机对照试验（iRCT）有效，但cRCT测量直接和间接疫苗效应的能力可能会减轻群集导致的效率损失。在cRCT中，聚类的数量和大小影响功效的3个决定因素：测量的效应量、疾病发生率和聚类内相关性。我们模拟了在一组小型社区中进行的试验，以评估在新出现的流行病期间，间接保护和聚类如何影响cRCT和iRCT的效力。在不同的参数中，我们发现在相同的试验人群中，cRCT从未比iRCT更有效，尽管差异可能很小。我们还确定了2种效应，这些效应减弱了传统上与簇大小增加相关的cRCT功率损失。首先，如果进行更少、更大集群的招募以在接种疫苗的社区内实现更高的疫苗覆盖率，这将增加待测量的效果，从而增加功效。第二，在较大的社区中输入传播率较高，可能会增加攻击率，并类似地减轻相对于在许多较小社区中进行试验的功率损失。
Power considerations for trials evaluating vaccines against infectious diseases are complicated by indirect protective effects of vaccination. While cluster-randomized controlled trials (cRCTs) are less statistically efficient than individually randomized controlled trials (iRCTs), a cRCT's ability to measure direct and indirect vaccine effects may mitigate the loss of efficiency due to clustering. Within cRCTs, the number and size of clusters affects 3 determinants of power: the effect size being measured, disease incidence, and intracluster correlation. We simulated trials conducted in a collection of small communities to assess how indirect protection and clustering affected the power of cRCTs and iRCTs during an emerging epidemic. Across diverse parameters, we found that within the same trial population, cRCTs were never more powerful than iRCTs, although the difference can be small. We also identified 2 effects that attenuated the loss of cRCT power traditionally associated with increased cluster size. First, if enrollment of fewer, larger clusters was performed to achieve higher vaccine coverage within vaccinated communities, this increased the effect to be measured and, consequently, power. Second, the greater rate of imported transmission in larger communities may increase the attack rate and similarly mitigate loss of power relative to a trial in many, smaller communities.