In 2019, the World Health Organization identified dengue as one of the top ten global health threats. For the control of dengue, the Applying Wolbachia to Eliminate Dengue (AWED) study group conducted a cluster-randomized trial in Yogyakarta, Indonesia, and used a novel design, called the cluster-randomized test-negative design (CR-TND). This design can yield valid statistical inference with data collected by a passive surveillance system and thus has the advantage of cost-efficiency compared to traditional cluster-randomized trials. We investigate the statistical assumptions and properties of CR-TND under a randomization inference framework, which is known to be robust and efficient for small-sample problems. We find that, when the differential healthcare-seeking behavior comparing intervention and control varies across clusters (in contrast to the setting of Dufault and Jewell, 2020 where the differential healthcare-seeking behavior is constant across clusters), current analysis methods for CR-TND can be biased and have inflated type I error. We propose the log-contrast estimator that can eliminate such bias and improve precision by adjusting for covariates. Furthermore, we extend our methods to handle partial intervention compliance and a stepped-wedge design, both of which appear frequently in cluster-randomized trials. Finally, we demonstrate our results by simulation studies and re-analysis of the AWED study.
翻译:2019年,世界卫生组织将登革热确定为十大全球健康威胁之一。为了控制登革热,“应用沃尔巴奇亚消灭登革热”研究小组在印度尼西亚日惹开展了一个集束随机试验,并使用了一个叫作集束随机试验负负设计(CR-TND)的新颖设计。这一设计可以对被动监测系统收集的数据产生有效的统计推断,因此与传统的集束随机试验相比,具有成本效益的优势。我们在一个随机推断框架下调查CR-TND的统计假设和特性,人们知道这个框架对小型抽样问题来说是稳健和高效的。我们发现,当对干预和控制进行比较的不同保健行为(与2020年Dufault和Jewel的设置不同)时,这一设计可以产生有效的统计推断,而目前对CR-TND的分析方法可能是偏差的,并且增加了I型误差。我们建议对CR-TND的统计估算师在随机推断框架中可以消除这种偏差和精确性,而人们知道它对小型抽样问题的判断框架是稳健而有效的。我们发现,当寻求保健行为对干预的差别和精确性研究时,我们通过不断调整的模拟研究,从而开始对A-C-A-A-A-A-G-G-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-S-A-A-A-A-A-A-A-A-A-S-A-S-A-A-A-A-C-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-C-A-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-S-的