Improving small-sample inference in group randomized trials with binary outcomes

Group Randomized Trials (GRTs) randomize groups of people to treatment or control arms instead of individually randomizing subjects. When each subject has a binary outcome, over-dispersed binomial data may result, quantified as an intra-cluster correlation (ICC). Typically, GRTs have a small number, n, of independent clusters, each of which can be quite large. Treating the ICC as a nuisance parameter, inference for a treatment effect can be done using quasi-likelihood with a logistic link. A Wald statistic, which, under standard regularity conditions, has an asymptotic standard normal distribution, can be used to test for a marginal treatment effect. However, we have found in our setting that the Wald statistic may have a variance less than 1, resulting in a test size smaller than its nominal value. This problem is most apparent when marginal probabilities are close to 0 or 1, particularly when n is small and the ICC is not negligible. When the ICC is known, we develop a method for adjusting the estimated standard error appropriately such that the Wald statistic will approximately have a standard normal distribution. We also propose ways to handle non-nominal test sizes when the ICC is estimated. We demonstrate the utility of our methods through simulation results covering a variety of realistic settings for GRTs. Copyright (C) 2010 John Wiley & Sons, Ltd.