title: Test and power considerations for multiple endpoint analyses using sequentially rejective graphical procedures.
abstract: A variety of powerful test procedures are available for the analysis of clinical trials addressing multiple objectives, such as comparing several treatments with a control, assessing the benefit of a new drug for more than one endpoint, etc. However, some of these procedures have reached a level of complexity that makes it difficult to communicate the underlying test strategies to clinical teams. Graphical approaches have been proposed instead that facilitate the derivation and communication of Bonferroni-based closed test procedures. In this paper we give a coherent description of the methodology and illustrate it with a real clinical trial example. We further discuss suitable power measures for clinical trials with multiple primary and/or secondary objectives and use a generic example to illustrate our considerations.
authors.affiliation: Statistical Methodology, Novartis Pharma AG, Lichstr. 35, CH-4002 Basel, Switzerland. frank.bretz@novartis.com
authors.forename: Frank
authors.initials: F
authors.lastname: Bretz
authors.forename: Willi
authors.initials: W
authors.lastname: Maurer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hommel
mesh_terms: D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003196:Computer Graphics; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D004358:Drug Therapy / Q000592:standards; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000379:methods*