A mixed model formulation for designing cluster randomized trials with binary outcomes

Abstract

Cluster randomized trials (CRTs) are unlike traditional individually randomized trials because observations within the same cluster are positively correlated and the sample size (number of clusters) is relatively small. Although formulae for sample size and power estimates of CRT designs do exist, these formulae rely upon first-order asymptotic approximations for the distribution of the average intervention effect and are inaccurate for CRTs that have a small number of clusters. These formulae also assume that the intracluster correlation (ICC) is the same for each cluster in the CRT. However, for CRTs in which the clusters are classrooms or medical practices, the degree of ICC is often a factor of how many students are in each classroom or how many patients are in each practice. Specifically, smaller clusters are expected to have larger ICC than larger clusters. A weighted sum of the cluster means, D, is the statistic often used to estimate the average intervention effect in a CRT. Therefore, we propose that a saddlepoint approximation is a natural choice to approximate the distributions of the cluster means more precisely than a standard large-sample approximation. We parameterize the ICC for each cluster as a random effect with a predefined prior distribution that is dependent upon the size of each cluster. After integrating over the range of the random effect, we use Monte Carlo methods to generate sample cluster means, which are in turn used to approximate the distribution of D with saddlepoint methods. Through numerical examples and an actual application, we show that our method has accuracy that is equal to or better than that of existing methods. Futhermore, our method accommodates CRTs in which the correlation within cluster is expected to diminish with the cluster size.