Estimation of Treatment and Carryover Effects in Optimal Cross-Over Designs for Clinical Trials
A particular multi-period cross-over design useful in trials where naturally observations are correlated and carryover effect may not die after one period, such as, Thorough QT, trials on diet, asthma and others, is shown to be useful for estimation in three practical cases. The cases are, the variance balanced estimation of direct and carryover treatment effects in presence of higher order carryover and correlated errors using ordinary least squares method, estimation of the said treatment effects under scattered missing, and, the interim estimation of the same for trials with early stopping rules. Comparison of treatment effect estimates and their variances is made with those given in literature for the higher order carryover model. A numerical example demonstrating estimation in all three cases is given.