Fig. 1.

Correction for the bias of the scaled difference between the means. Reference-scaled differences, (Y _T − Y _R)/s _R were estimated from 25,000 simulated four-period crossover trials by standard ANOVA. The plug-in estimator for reference-scaled difference is the ratio of the corresponding least-squares estimates of Y _T − Y _R and s _R. The estimated scaled difference was divided by the true value used in the simulations. The squares in the figure represent the means of the simulations; the continuous curve is the value predicted by Eqs. 9a and 9b. Simulation conditions: n = 40, s _R and s _T = 0.4, GMR = 1