title: Multiplicity: discussion points from the Statisticians in the Pharmaceutical Industry multiplicity expert group.
abstract: In May 2012, the Committee of Health and Medicinal Products issued a concept paper on the need to review the points to consider document on multiplicity issues in clinical trials. In preparation for the release of the updated guidance document, Statisticians in the Pharmaceutical Industry held a one-day expert group meeting in January 2013. Topics debated included multiplicity and the drug development process, the usefulness and limitations of newly developed strategies to deal with multiplicity, multiplicity issues arising from interim decisions and multiregional development, and the need for simultaneous confidence intervals (CIs) corresponding to multiple test procedures. A clear message from the meeting was that multiplicity adjustments need to be considered when the intention is to make a formal statement about efficacy or safety based on hypothesis tests. Statisticians have a key role when designing studies to assess what adjustment really means in the context of the research being conducted. More thought during the planning phase needs to be given to multiplicity adjustments for secondary endpoints given these are increasing in importance in differentiating products in the market place. No consensus was reached on the role of simultaneous CIs in the context of superiority trials. It was argued that unadjusted intervals should be employed as the primary purpose of the intervals is estimation, while the purpose of hypothesis testing is to formally establish an effect. The opposing view was that CIs should correspond to the test decision whenever possible.
authors.affiliation: ICON Clinical Research, Marlow, Buckinghamshire, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Phillips
authors.forename: Chrissie
authors.initials: C
authors.lastname: Fletcher
authors.forename: Gary
authors.initials: G
authors.lastname: Atkinson
authors.forename: Eddie
authors.initials: E
authors.lastname: Channon
authors.forename: Abdel
authors.initials: A
authors.lastname: Douiri
authors.forename: Thomas
authors.initials: T
authors.lastname: Jaki
authors.forename: Jeff
authors.initials: J
authors.lastname: Maca
authors.forename: David
authors.initials: D
authors.lastname: Morgan
authors.forename: James Henry
authors.initials: JH
authors.lastname: Roger
authors.forename: Paul
authors.initials: P
authors.lastname: Terrill
mesh_terms: D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D016001:Confidence Intervals; D004345:Drug Industry / Q000706:statistics & numerical data*; D006801:Humans; D012107:Research Design / Q000706:statistics & numerical data*; D012108:Research Personnel
keywords: hypothesis tests; multiplicity; secondary endpoints; simultaneous CIs; type I error