The probability of observing negative subgroup results when the treatment effect is positive and homogeneous across all subgroups

作     者：Li, Zhengqing Chuang-Stein, Christy Hoseyni, Cyrus 

作者机构：Bristol Myers Squibb Co Global Biometr Sci Wallingford CT 06492 USA Pfizer Global Res & Dev Clin Stat Ann Arbor MI USA Wyeth Pharmaceut Global Biostat & Programming Collegeville PA USA 

出 版 物：《DRUG INFORMATION JOURNAL》 (药物信息杂志)

年 卷 期：2007年第41卷第1期

页      面：47-56页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1204[管理学-公共管理] 10[医学] 

主　　题：conditional probability effect size exploratory false-negative power 

摘      要：Subgroup analysis is an important part in the design and analysis of clinical trials. The importance arises from the scientific and commercial implications of such analysis. The predominant concerns about subgroup analysis related to the increased false-positive and false-negative rates. Much of the existing literature on subgroup analysis focuses on the former. In this article, we will concentrate on the false-negative aspect. Using theoretical derivation and simulations, we investigate factors that affect the probability of observing at least one negative subgroup result (ie, numerically negative treatment effect estimate) even though the true treatment effect is positive (ie, the new treatment is more efficacious than the comparator) and homogeneous across all subgroups. This probability, conditioning or unconditioning on a statistically significant overall treatment effect, is assessed for design scenarios that are commonly encountered in practice. In additions, we assess the probability of observing at least one statistically significant negative sub-group result, again conditioning or unconditioning on a statistically significant overall treatment effect. We submit that knowledge of such probabilities could provide clinical researchers with insight into the reliability of subgroup results and help set proper expectations vis-a-vis such analysis. The later facilitates a balanced interpretation of subgroup results.