title: Adaptive choice of patient subgroup for comparing two treatments.
abstract: This paper is motivated by a randomized controlled trial to compare an endovascular procedure with conventional medical treatment for stroke patients, in which the endovascular procedure may be effective only in a subgroup of patients. Since the subgroup is not known at the design stage but can be learned statistically from the data collected during the course of the trial, we develop a novel group sequential design that incorporates adaptive choice of the patient subgroup among several possibilities which include the entire patient population as a choice. We define the type I and type II errors of a test in this design and show how a prescribed type I error can be maintained by using the closed testing principle in multiple testing. We also show how asymptotically optimal tests can be constructed by using generalized likelihood ratio statistics for parametric problems and analogous standardized or Studentized statistics for nonparametric tests such as Wilcoxon's rank sum test commonly used for treatment comparison in stroke patients.
authors.affiliation: Department of Statistics, Stanford University, Stanford, CA, USA.
authors.forename: Tze Leung
authors.initials: TL
authors.lastname: Lai
authors.affiliation: Department of Health Research Policy, Stanford University, Stanford, CA, USA.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Lavori
authors.affiliation: Onyx Pharmaceuticals, South San Francisco, CA, USA. Electronic address: oliao@onyx.com.
authors.forename: Olivia Yueh-Wen
authors.initials: OY
authors.lastname: Liao
mesh_terms: D002755:Choice Behavior; D003198:Computer Simulation; D057510:Endovascular Procedures / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging; D015233:Models, Statistical; D012107:Research Design; D018401:Sample Size; D018709:Statistics, Nonparametric; D020521:Stroke / Q000188:drug therapy* / Q000601:surgery*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
chemical_list: D010959:Tissue Plasminogen Activator
keywords: Adaptive selection; Generalized likelihood ratio statistics; Group sequential design; Kullback–Leibler information; Multiple testing; Normalized Wilcoxon statistic