DESIGN CONSIDERATIONS IN CROSSOVER TRIALS WITH A SINGLE INTERIM ANALYSIS AND SERIAL PATIENT ENTRY

A two-stage sequential design is presented to facilitate a single inte rim analysis in crossover trials with serial patient entry. The interi m analysis is based on a linear statistic that combines data from indi viduals observed for only one treatment period with data from those ob served for both periods (Cook, R. J., 1995, Biometrics 51, 932-945). T he final analysis is based on the usual test statistic used in Crossov er trials. The size of this procedure is controlled by partitioning th e experimental type I error rate over the two analyses and deriving th e appropriate critical values. We investigate the design implications of adopting this procedure over the usual analysis for crossover trial s by examining the necessary sample size inflation factors to maintain power, and indicate the expected savings in terms of the number of re sponses required. Data from a study designed to compare two antiemetic therapies for previously untreated chemotherapy patients (Osaba, D., et al., 1986, Clinical and Investigative Medicine 9, 225-231) are used to illustrate the procedure.