Formal approaches to safety monitoring of clinical trials in life-threatening conditions

作     者：Bolland, K Whitehead, J 

作者机构：Univ Reading Med & Pharmaceut Stat Res Unit Reading RG6 6FN Berks England 

出 版 物：《STATISTICS IN MEDICINE》 (医学统计学)

年 卷 期：2000年第19卷第21期

页      面：2899-2917页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 0714[理学-统计学（可授理学、经济学学位）] 10[医学] 

主　　题：临床试验(主题)/统计学和数值数据 临床试验 Ⅲ期(主题)/统计学和数值数据 颅脑损伤/药物疗法 颅脑损伤/死亡率 数据说明 统计 模型 统计学 多中心研究(主题)/统计学和数值数据 心肌梗死/药物疗法 心肌梗死/死亡率 正态分布 概率 安全/统计学和数值数据 卒中/药物疗法 卒中/死亡率 人类 

摘      要：Large clinical trials in life-threatening conditions are usually conducted under the surveillance of a Data and Safety Monitoring Board (DSMB), whose remit is to protect the ethical and safety interests of the patients. The purpose of this paper is to describe a formal approach to safety monitoring, using a sequential safety procedure to aid the decisions made by the DSMB. This procedure is designed to recommend termination of the study as soon as evidence that the experimental treatment is worse than the control in terms of the primary safety response is so strong that it is unethical to proceed. The use of this formal sequential procedure enables probabilities of the study stopping erroneously and stopping correctly, under various degrees of experimental treatment disadvantage, to be examined. Also scenarios depicting data sets which lead to continuing or stopping can be presented. Such explorations are useful in encouraging all DSMB members to consider carefully, prior to the start of a study, the conditions under which they would seriously wish to consider termination. The implementation of these methods is described for three recently completed trials in which it has been used. Finally, our current recommendations for the design of these procedures, arising from these and other similar experiences, are given. Copyright (C) 2000 John Wiley & Sons, Ltd.