title: Power of an Adaptive Trial Design for Endovascular Stroke Studies: Simulations Using IMS (Interventional Management of Stroke) III Data.
abstract: Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies.
  
  
  
  We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design.
  
  
  
  The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%).
  
  
  
  These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern.
authors.affiliation: From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.). lansberg@stanford.edu.
authors.forename: Maarten G
authors.initials: MG
authors.lastname: Lansberg
authors.affiliation: From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.).
authors.forename: Ninad S
authors.initials: NS
authors.lastname: Bhat
authors.affiliation: From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.).
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Yeatts
authors.affiliation: From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.).
authors.forename: Yuko Y
authors.initials: YY
authors.lastname: Palesch
authors.affiliation: From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.).
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
authors.affiliation: From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.).
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Albers
authors.affiliation: From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.).
authors.forename: Tze L
authors.initials: TL
authors.lastname: Lai
authors.affiliation: From the Stanford Stroke Center, School of Medicine (M.G.L., N.S.B., G.W.A.), Department of Statistics (T.L.L., P.W.L.), Department of Biomedical Data Science, School of Medicine (T.L.L., P.W.L.), Stanford University, CA; Department of Public Health Sciences, Medical University of South Carolina, Charleston (S.D.Y., Y.Y.P.); and Department of Neurology, University of Cincinnati Medical Center, OH (J.P.B.).
authors.forename: Philip W
authors.initials: PW
authors.lastname: Lavori
mesh_terms: D002986:Clinical Trials as Topic / Q000592:standards / Q000706:statistics & numerical data*; D003198:Computer Simulation; D057510:Endovascular Procedures / Q000706:statistics & numerical data*; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000592:standards / Q000706:statistics & numerical data*; D012107:Research Design / Q000592:standards / Q000706:statistics & numerical data*; D020521:Stroke / Q000145:classification / Q000000981:diagnostic imaging* / Q000628:therapy*
keywords: adaptive trial design; endovascular techniques; stroke