SOME STATISTICAL-METHODS FOR MULTIPLE END-POINTS IN CLINICAL-TRIALS

This paper summarizes, defines, and discusses multiple endpoints compa rison procedures, concepts, and methodologies for applications to clin ical trials. We address the more widely used methods of alpha-level, p -value, and critical value adjustments. We examine global assessment m easures such as O'Brien's test and Simes' procedure and contrast them with the alpha-adjustment procedures of Bonferroni and Helm. We propos e a global assessment procedure based on categorization of the individ ual endpoints to form an overall composite endpoint. Additionally, we discuss a new weighting scheme for Helm's sequentially rejective alpha -adjustment procedure. investigation of the correlation between endpoi nts is examined in relation to adjustment of the alpha-level. In the c ontext of a clinical trial, the above multiplicity procedures are appl ied and compared. Finally, some comments concerning ease of use and re levance are summarized for the above methods. (C) Elsevier Science Inc . 1997.