Teerenstra Steven, Lu Bing, Preisser John S, van Achterberg Theo, Borm George F
Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Biometrics. 2010 Dec;66(4):1230-7. doi: 10.1111/j.1541-0420.2009.01374.x.
Cluster randomized trials in health care may involve three instead of two levels, for instance, in trials where different interventions to improve quality of care are compared. In such trials, the intervention is implemented in health care units ("clusters") and aims at changing the behavior of health care professionals working in this unit ("subjects"), while the effects are measured at the patient level ("evaluations"). Within the generalized estimating equations approach, we derive a sample size formula that accounts for two levels of clustering: that of subjects within clusters and that of evaluations within subjects. The formula reveals that sample size is inflated, relative to a design with completely independent evaluations, by a multiplicative term that can be expressed as a product of two variance inflation factors, one that quantifies the impact of within-subject correlation of evaluations on the variance of subject-level means and the other that quantifies the impact of the correlation between subject-level means on the variance of the cluster means. Power levels as predicted by the sample size formula agreed well with the simulated power for more than 10 clusters in total, when data were analyzed using bias-corrected estimating equations for the correlation parameters in combination with the model-based covariance estimator or the sandwich estimator with a finite sample correction.
医疗保健领域的整群随机试验可能涉及三个而非两个层次,例如,在比较不同改善医疗质量干预措施的试验中。在此类试验中,干预措施在医疗保健单位(“群组”)中实施,旨在改变在该单位工作的医疗保健专业人员(“受试者”)的行为,而效果则在患者层面进行测量(“评估”)。在广义估计方程方法中,我们推导了一个样本量公式,该公式考虑了两个层次的聚类:群组内受试者的聚类以及受试者内评估的聚类。该公式表明,相对于完全独立评估的设计,样本量会因一个乘法项而膨胀,这个乘法项可表示为两个方差膨胀因子的乘积,一个量化评估的受试者内相关性对受试者层面均值方差的影响,另一个量化受试者层面均值之间的相关性对群组均值方差的影响。当使用针对相关参数的偏差校正估计方程结合基于模型的协方差估计器或具有有限样本校正的三明治估计器对数据进行分析时,对于总共超过10个群组的情况,样本量公式预测的功效水平与模拟功效非常吻合。