title: Estimation after blinded sample size reassessment.
abstract: Blinded sample size reassessment is a popular means to control the power in clinical trials if no reliable information on nuisance parameters is available in the planning phase. We investigate how sample size reassessment based on blinded interim data affects the properties of point estimates and confidence intervals for parallel group superiority trials comparing the means of a normal endpoint. We evaluate the properties of two standard reassessment rules that are based on the sample size formula of the z-test, derive the worst case reassessment rule that maximizes the absolute mean bias and obtain an upper bound for the mean bias of the treatment effect estimate.
authors.affiliation: 1 Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Posch
authors.affiliation: 1 Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.|2 Department of Statistical Sciences, University of Padua, Padua, Italy.
authors.forename: Florian
authors.initials: F
authors.lastname: Klinglmueller
authors.affiliation: 1 Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: König
authors.affiliation: 3 Department of Statistics, Stockholm University, Stockholm, Sweden Martin Posch and Florian Klinglmueller share first authorship.
authors.forename: Frank
authors.initials: F
authors.lastname: Miller
mesh_terms: D000465:Algorithms; D015982:Bias; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D015233:Models, Statistical; D010865:Pilot Projects; D012107:Research Design; D018401:Sample Size
keywords: Adaptive design; interim analysis; internal pilot study; point estimate; sample size reassessment