310058Department of Biostatistics, 50296Yale University School of Public Health, New Haven, CT, USA.
5755Yale Center for Analytical Sciences, New Haven, CT, USA.
Stat Methods Med Res. 2022 Jul;31(7):1224-1241. doi: 10.1177/09622802221085080. Epub 2022 Mar 15.
While statistical methods for analyzing cluster randomized trials with continuous and binary outcomes have been extensively studied and compared, little comparative evidence has been provided for analyzing cluster randomized trials with survival outcomes in the presence of competing risks. Motivated by the Strategies to Reduce Injuries and Develop Confidence in Elders trial, we carried out a simulation study to compare the operating characteristics of several existing population-averaged survival models, including the marginal Cox, marginal Fine and Gray, and marginal multi-state models. For each model, we found that adjusting for the intraclass correlations through the sandwich variance estimator effectively maintained the type I error rate when the number of clusters is large. With no more than 30 clusters, however, the sandwich variance estimator can exhibit notable negative bias, and a permutation test provides better control of type I error inflation. Under the alternative, the power for each model is differentially affected by two types of intraclass correlations-the within-individual and between-individual correlations. Furthermore, the marginal Fine and Gray model occasionally leads to higher power than the marginal Cox model or the marginal multi-state model, especially when the competing event rate is high. Finally, we provide an illustrative analysis of Strategies to Reduce Injuries and Develop Confidence in Elders trial using each analytical strategy considered.
虽然已经广泛研究和比较了用于分析连续性和二分类结局的整群随机试验的统计方法，但对于分析存在竞争风险的生存结局的整群随机试验，提供的比较证据很少。受 Strategies to Reduce Injuries and Develop Confidence in Elders 试验的启发，我们进行了一项模拟研究，以比较几种现有的基于人群的生存模型的特征，包括边缘 Cox 模型、边缘 Fine-Gray 模型和边缘多状态模型。对于每种模型，我们发现，通过 sandwich 方差估计器调整组内相关系数可以在聚类数较大时有效保持Ⅰ型错误率。然而，当聚类数不超过 30 时，sandwich 方差估计器可能会出现显著的负偏倚，而置换检验可以更好地控制Ⅰ型错误膨胀。在备择假设下，每种模型的功效都受到两种类型的组内相关系数（个体内和个体间相关系数）的不同影响。此外，边缘 Fine-Gray 模型偶尔会比边缘 Cox 模型或边缘多状态模型具有更高的功效，尤其是在竞争事件率较高时。最后，我们使用每种分析策略对 Strategies to Reduce Injuries and Develop Confidence in Elders 试验进行了说明性分析。
