Estimation of Treatment and Carryover Effects in Optimal Cross-Over Designs for Clinical Trials

Abstract

A particular multi-period cross-over design useful in trials where observations naturally 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 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.