Methodological quality of animal studies of neuroprotective agents currently in phase II/III acute ischemic stroke trials

Maria Philip, Michael G Benatar, Marc Fisher, Sean I. Savitz

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Background and Purpose-Numerous neuroprotective agents have proven effective in animal stroke studies, but every drug has failed to achieve its primary outcome when brought forward to clinical trials. We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials. Methods-We conducted a systematic search of all neuroprotective drugs in Phase II or III trials and collected data from animal studies of focal cerebral ischemia testing agents systemically administered within 24 hours of occlusion. The methodological rigor of each individual study was evaluated using 5 criteria derived from the STAIR guidelines. The adequacy of the preclinical "package" for each drug was then evaluated by combining the results of all studies for each drug to determine which of a further 5 STAIR criteria were met before moving forward from animal to human studies. Results-Our search yielded 13 agents of which 10 had published data in peer-reviewed journals. There is substantial within-drug variability in the quality of preclinical studies as well as substantial variation in the completeness of the collective preclinical literature for different drugs. There has been little or no improvement in the quality of animal studies since NXY-059, and current agents have not been subjected to a more complete preclinical evaluation. Conclusion-There is significant heterogeneity in the quality of animal testing for neuroprotective agents in stroke. Drugs in the post-SAINT era have not been subjected to more thorough preclinical evaluation.

Original languageEnglish
Pages (from-to)577-581
Number of pages5
JournalStroke
Volume40
Issue number2
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

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Neuroprotective Agents
Stroke
Pharmaceutical Preparations
Quality Improvement
Brain Ischemia
Clinical Trials
Guidelines

Keywords

  • , animal model
  • Focal cerebral ischemia
  • Neuroprotection
  • Quality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Methodological quality of animal studies of neuroprotective agents currently in phase II/III acute ischemic stroke trials. / Philip, Maria; Benatar, Michael G; Fisher, Marc; Savitz, Sean I.

In: Stroke, Vol. 40, No. 2, 01.02.2009, p. 577-581.

Research output: Contribution to journalArticle

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