title: Analysis of early phase and subsequent phase III stroke studies of neuroprotectants: outcomes and predictors for success.
abstract: BACKGROUND
  Efficacy of neuroprotective treatments for ischemic stroke was not convincingly demonstrated in clinical phase III trials so far, whereas some preceding early phase studies found neuroprotection to be beneficial. We aimed to determine the frequency with which phase III studies are preceded by positive early phase studies, and to identify characteristics of early phase studies that are associated with correct prediction of phase III studies.
  
  
  METHODS
  We identified phase III studies and corresponding early phase studies of neuroprotective treatments for stroke. Data on study characteristics of early phase trials were extracted and compared between studies that were classified according to their results as "false positive" and "true neutral" using logistic regression analysis.
  
  
  RESULTS
  Forty-six phase III studies and 59 corresponding early phase studies were identified. Only one phase III study was positive and this study was followed by a larger negative study. Twenty-two (37.3%) early phase studies were considered to be false positive and 37 (62.7%) to be true neutral. None of the early phase study characteristics were significantly associated with correct prediction of phase III studies.
  
  
  CONCLUSIONS
  More than one third of early phase studies on neuroprotective stroke treatments are false positive. Neither the results nor specific study design characteristics of early phase stroke studies reliably predict success in phase III trials. Further efforts are needed to improve early phase studies regarding its predictability and to identify those early studies that should be advanced to phase III trials.
authors: Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany. minnerup@uni-muenster.de.
authors: Jens
authors: J
authors: Minnerup
authors: Heike
authors: H
authors: Wersching
authors: Matthias
authors: M
authors: Schilling
authors: Wolf Rüdiger
authors: WR
authors: Schäbitz