title: Some statistical methods for multiple endpoints in clinical trials.
abstract: This paper summarizes, defines, and discusses multiple endpoints comparison procedures, concepts, and methodologies for applications to clinical trials. We address the more widely used methods of alpha-level, p-value, and critical value adjustments. We examine global assessment measures such as O'Brien's test and Simes' procedure and contrast them with the alpha-adjustment procedures of Bonferroni and Holm. We propose a global assessment procedure based on categorization of the individual endpoints to form an overall composite endpoint. Additionally, we discuss a new weighting scheme for Holm's sequentially rejective alpha-adjustment procedure. Investigation of the correlation between endpoints is examined in relation to adjustment of the alpha-level. In the context of a clinical trial, the above multiplicity procedures are applied and compared. Finally, some comments concerning ease of use and relevance are summarized for the above methods.
authors.affiliation: Merck Research Laboratories, Clinical Biostatistics and Research Data Systems, Rahway, NJ 07065-0900, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Quan
authors.forename: J
authors.initials: J
authors.lastname: Ng
authors.forename: M E
authors.initials: ME
authors.lastname: Stepanavage
mesh_terms: D001249:Asthma / Q000188:drug therapy; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003625:Data Collection; D003627:Data Interpretation, Statistical; D004359:Drug Therapy, Combination; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D015233:Models, Statistical; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D016896:Treatment Outcome