Use of the two-stage procedure for analysis of cross-over trials in four aspects of medical statistics
The two-stage procedure had been used as a standard method to analyse cross-over trials for many years before its major deficiency was found. The inflated type I error rate of the two-stage procedure indicates that there have been more trials which have produced false positive results than originally believed. Because of the 24 years gap between the introduction of the method and the publishing of its deficiency, it is conceivable that the impact of the change in the perception about the validity of the two-stage procedure might not have taken effect overnight. The objective of this thesis is to examine the impact of the change in the perception about the validity of the two-stage procedure on four different aspects of medical statistics. The areas of medical statistics include both applications of, and references to, the analysis of cross-over trials to give a full picture of the use of the two-stage procedure. Methods used are citation analysis for all scientific journals, systematic review for medical journals, comprehensive review for general medical statistics books and questionnaire survey for the pharmaceutical industry. The results have been inconclusive in terms of the estimation of how prevalently the two-stage procedure has been used. However, the four studies demonstrated that the analysis of cross-over trials is often associated with the two-stage procedure while the deficiency of the two-stage procedure has not been generally acknowledged. It can be concluded that further understanding of Use of the two-stage procedure for analysis of cross-over trials in four aspects of medical statistics the two-stage procedure and better references in the analysis of cross-over trials are needed in all four areas of medical statistics.