title: A proposed statistical framework for the management of subgroup analyses for large clinical trials.
abstract: Planned and unplanned subgroup analyses of large clinical trials are frequently performed and the results are sometimes difficult to interpret. The source of a nominal significant finding may come from a true signal, variation of the clinical trial outcome or the observed data structure. Quantitative assessment is critical to the interpretation of the totality of the clinical data. In this article we provide a general framework to manage subgroup analyses and to interpret the findings through a set of supplement analyses to planned main (primary and secondary) analyses, as an alternative to the commonly used multiple comparison framework. The proposed approach collectively and coherently utilizes several quantitative methods and enhances the credibility and interpretability of subgroup analyses. A case study is used to illustrate the application of the proposed method.
authors.affiliation: Celgene Corporation, 300 Connell Drive, Berkeley Heights, NJ 07922, United States. Electronic address: xluo@celgene.com.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Luo
authors.affiliation: Celgene Corporation, 300 Connell Drive, Berkeley Heights, NJ 07922, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Celgene Corporation, 300 Connell Drive, Berkeley Heights, NJ 07922, United States.
authors.forename: Alan Chengqing
authors.initials: AC
authors.lastname: Wu
authors.affiliation: Johnson & Johnson Company, United States.
authors.forename: Guohua
authors.initials: G
authors.lastname: Pan
authors.affiliation: Celgene Corporation, 300 Connell Drive, Berkeley Heights, NJ 07922, United States.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Li
authors.affiliation: Celgene Corporation, 300 Connell Drive, Berkeley Heights, NJ 07922, United States.
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Celgene Corporation, 300 Connell Drive, Berkeley Heights, NJ 07922, United States.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Celgene Corporation, 300 Connell Drive, Berkeley Heights, NJ 07922, United States.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Cline
authors.affiliation: Celgene Corporation, 300 Connell Drive, Berkeley Heights, NJ 07922, United States.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Dornseif
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, United States.
authors.forename: Zhezhen
authors.initials: Z
authors.lastname: Jin
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic; D017327:Clinical Trials, Phase IV as Topic; D003627:Data Interpretation, Statistical; D006801:Humans; D015337:Multicenter Studies as Topic / Q000379:methods*; D012107:Research Design
keywords: Expected variation; LASSO; Multi-regional trial; Quantitative and qualitative interaction; Subgroup analysis