Opportunities and challenges of clinical trials in cardiology using composite primary endpoints

作     者：Geraldine Rauch Bernhard Rauch Svenja Schüler Meinhard Kieser 

作者机构：Institute of Medical Biometry and InformaticsUniversity of HeidelbergD-69120 HeidelbergGermany Institut für HerzinfarktforschungD-67063 LudwigshafenGermany 

出 版 物：《World Journal of Cardiology》 (世界心脏病学杂志（英文版）（电子版）)

年 卷 期：2015年第7卷第1期

页      面：1-5页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：Composite endpoint Competing risks Multiple testing Time-to-event Adaptive designs 

摘      要：In clinical trials, the primary efficacy endpoint often corresponds to a so-called composite endpoint. Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, asthe expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.