Using second-order generalized estimating equations to model heterogeneous intraclass correlation in cluster-randomized trials

In cluster-randomized trials, it is commonly assumed that the magnitude of the correlation among subjects within a cluster is constant across clusters. However, the correlation may in fact be heterogeneous and depend on cluster characteristics. Accurate modeling of the correlation has the potential to improve inference. We use second-order generalized estimating equations to model heterogeneous correlation in cluster-randomized trials. Using, simulation studies we show that accurate modeling of heterogeneous correlation can improve inference when the correlation is high or varies by cluster size. We apply the methods to a cluster-randomized trial of an intervention to promote breast cancer screening. Copyright (C) 2008 John Wiley & Sons, Ltd.