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 observations naturally are correlated and carryover effect may not die after one periodsuch as thorough QT, trials on diet, asthma, and othersis 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 observations; and the interim estimation of the same for trials with early stopping rules. We compare treatment effect estimates and their variances with those given in the literature for the higher-order carryover model. We also give a numerical example demonstrating estimation in all three cases.