
138 Sample Size Calculations for Clustered and Longitudinal Outcomes
calculation for multi-level clustered trial using linear mixed models can be
found in Heo and Leon [74].
A potential future development of GEE sample size calculation is the re-
estimation of variance matrix and subsequently, the sample size, based on
interim data. The estimation of sample size in clinical trials requires knowl-
edge of parameters that involve treatment effect, variability, and correlation
(for clustered/longitudinal measurements), which are usually uncertain to re-
searchers at the design stage. This uncertainty is especially pronounced for
clinical trials with new ...