title: Applying a phase II futility study design to therapeutic stroke trials.
abstract: OBJECTIVE
  Most large, randomized phase III efficacy trials of therapeutic agents in ischemic stroke have failed to find treatment benefit. We determined whether some phase III studies could have been avoided if preceded by smaller single-arm phase II studies to evaluate the futility of proceeding to phase III.
  
  
  METHODS
  To provide examples of the application of phase II methodology, we obtained primary outcome data for the active treatment group of 6 phase III ischemic stroke therapy trials. For each study, we estimated the sample size number required for a multistage single-arm study using parameters specified in the original study. We evaluated outcome data for the first number of subjects in the phase III study treatment arm ordered by enrollment dates. We compared the proportion of favorable outcomes to prespecified stopping criteria derived from a single-arm phase II futility design. If the observed proportion of favorable outcomes was less than the stopping criterion, we declared the treatment not sufficiently effective to warrant further evaluation in phase III.
  
  
  RESULTS
  We identified 3 trials as futile in phase II; none of 3 showed treatment efficacy in phase III. In the 3 remaining phase II trials in which we did not show futility, one showed efficacy in phase III.
  
  
  CONCLUSIONS
  Single-arm phase II futility studies have been underused in stroke research, but provide a strategy for discarding treatments likely to be ineffective in phase III trials.
authors.affiliation: Department of Biostatistics, Bioinformatics & Epidemiology, Medical University of South Carolina, P.O. Box 250835, Charleston, SC 29425, USA. paleschy@musc.edu
authors.forename: Yuko Y
authors.initials: YY
authors.lastname: Palesch
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Tilley
authors.forename: David L
authors.initials: DL
authors.lastname: Sackett
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnston
authors.forename: Robert
authors.initials: R
authors.lastname: Woolson
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003198:Computer Simulation; D006801:Humans; D018447:Medical Futility; D015233:Models, Statistical; D011788:Quality of Life; D012107:Research Design; D018401:Sample Size; D012680:Sensitivity and Specificity; D020521:Stroke / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome