Repeated measures in clinical trials: analysis using mean summary statistics and its implications for design.

This paper explores the use of simple summary statistics for analysing repeated measurements in randomized clinical trials with two treatments. Quite often the data for each patient may be effectively summarized by a pre-treatment mean and a post-treatment mean. Analysis of covariance is the method of choice and its superiority over analysis of post-treatment means or analysis of mean changes is quantified, as regards both reduced variance and avoidance of bias, using a simple model for the covariance structure between time points. Quantitative consideration is also given to practical issues in the design of repeated measures studies: the merits of having more than one pre-treatment measurement are demonstrated, and methods for determining sample sizes in repeated measures designs are provided. Several examples from clinical trials are presented, and broad practical recommendations are made. The examples support the value of the compound symmetry assumption as a realistic simplification in quantitative planning of repeated measures trials. The analysis using summary statistics makes no such assumption. However, allowance in design for alternative non-equal correlation structures can and should be made when necessary.