Analysis of early phase and subsequent phase III stroke studies of neuroprotectants: outcomes and predictors for success

Experimental & Translational Stroke Medicine

Wolf Rüdiger Schäbitz¹  Matthias Schilling³  Heike Wersching²  Jens Minnerup³ 

[1] Department of Neurology, Bethel, Burgsteig 13, 33617 Bielefeld, Germany;Institute of Epidemiology and Social Medicine, University of Münster, Domagkstrasse 3, 48149 Münster, Germany;Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany

关键词: Prediction of trial results;    Clinical trial design;    Neuroprotection;    Stroke;   

Others  :  861430
DOI  :  10.1186/2040-7378-6-2

 received in 2014-02-03, accepted in 2014-02-04,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Minnerup et al.; licensee BioMed Central Ltd.

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