Hybrid sample size calculations for cluster randomised trials using assurance

Abstract

Sample size determination for cluster randomised trials (CRTs) is challenging as it requires robust estimation of the intra-cluster correlation coefficient (ICC). Typically, the sample size is chosen to provide a certain level of power to reject the null hypothesis in a hypothesis test. This relies on the minimal clinically important difference (MCID) and estimates for the standard deviation, ICC and possibly the coefficient of variation of the cluster size. Varying these parameters can have a strong effect on the sample size. In particular, it is sensitive to small differences in the ICC. A relevant ICC estimate is often not available, or the available estimate is imprecise. If the ICC used is far from the unknown true value, this can lead to trials which are substantially over- or under-powered. We propose a hybrid approach using Bayesian assurance to find the sample size for a CRT with a frequentist analysis. Assurance is an alternative to power which incorporates uncertainty on parameters through a prior distribution. We suggest specifying prior distributions for the standard deviation, ICC and coefficient of variation of the cluster size, while still utilising the MCID. We illustrate the approach through the design of a CRT in post-stroke incontinence. We show assurance can be used to find a sample size based on an elicited prior distribution for the ICC, when a power calculation discards all information in the prior except a single point estimate. Results show that this approach can avoid misspecifying sample sizes when prior medians for the ICC are very similar but prior distributions exhibit quite different behaviour. Assurance provides an understanding of the probability of success of a trial given an MCID and can be used to produce sample sizes which are robust to parameter uncertainty. This is especially useful when there is difficulty obtaining reliable parameter estimates.