Background: Target trial emulation (TTE) that applies trial design principles to improve the analysis of non-randomized studies is increasingly being used. Applications of TTE to emulate cluster randomized trials (RCTs) have been limited. This study explored how to integrate simulation-guided design into the TTE framework to inform planning of a non-randomized cluster trial. Methods: We performed simulations to prospectively plan data collection of a non-randomized study emulating a village-level cluster RCT when cluster-randomization was infeasible. The planned study will assess the impact of mass distribution of nutritional supplements embedded within an existing immunization program to improve pentavalent vaccination rates among children 12-24 months old in Niger. The design included covariate-constrained random selection of villages for outcome ascertainment at follow-up. Simulations used baseline census data on pentavalent vaccination rates and cluster-level covariates to compare the type I error rate and power of four statistical methods: beta-regression; quasi-binomial regression; inverse probability of treatment weighting (IPTW); and naive Wald test. Results: Of the four analytic methods considered, only IPTW and beta-regression controlled the type I error rate at 0.05, but IPTW yielded poor statistical power. Beta-regression that showed adequate statistical power was chosen as our primary analysis. Conclusions: Adopting simulation-guided design principles within TTE can enable robust planning of a group-level non-randomized study emulating a cluster RCT. Lessons from this study also apply to TTE planning of individually-RCTs.

翻译：背景：目标试验仿真（TTE）通过应用试验设计原则改进非随机研究的分析，其应用日益广泛。然而，TTE在模拟集群随机试验（RCT）方面的应用仍较为有限。本研究探讨了如何将模拟引导设计整合到TTE框架中，以指导非随机集群试验的规划。方法：在集群随机化不可行的情况下，我们通过模拟前瞻性规划了一项模拟村级集群RCT的非随机研究数据收集。该计划研究旨在评估在现有免疫规划中嵌入大规模营养补充剂分发对提高尼日尔12-24月龄儿童五联疫苗接种率的影响。设计包括采用协变量约束随机选择村庄进行随访结果确认。模拟利用五联疫苗接种率和集群层面协变量的基线普查数据，比较了四种统计方法的I类错误率和统计功效：贝塔回归、拟二项回归、逆概率处理加权（IPTW）以及朴素Wald检验。结果：在考虑的四种分析方法中，仅IPTW和贝塔回归将I类错误率控制在0.05水平，但IPTW的统计功效较低。贝塔回归显示出足够的统计功效，因此被选为主要分析方法。结论：在TTE中采用模拟引导设计原则能够实现对模拟集群RCT的组级非随机研究进行稳健规划。本研究的经验同样适用于个体层面RCT的TTE规划。