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Identifying stroke therapeutics from preclinical models: A protocol for a novel application of network meta-analysis

Research output: Contribution to journalArticle

  • Manoj M Lalu
  • Dean A Fergusson
  • Wei Cheng
  • Marc T Avey
  • Dale Corbett
  • Dar Dowlatshahi
  • Malcolm R Macleod
  • Emily S Sena
  • David Moher
  • Risa Shorr
  • Sarah K McCann
  • Laura J Gray
  • Michael D Hill
  • Annette O'Connor
  • Kristina Thayer
  • Fatima Haggar
  • Aditi Dobriyal
  • Hee Sahng Chung
  • Nicky J Welton
  • Brian Hutton
Original languageEnglish
Article number11
Number of pages14
DateAccepted/In press - 3 Jan 2019
DatePublished (current) - 3 Jan 2019


Introduction: Globally, stroke is the second leading cause of death. Despite the burden of illness and death, few acute interventions are available to patients with ischemic stroke. Over 1,000 potential neuroprotective therapeutics have been evaluated in preclinical models. It is important to use robust evidence synthesis methods to appropriately assess which therapies should be translated to the clinical setting for evaluation in human studies. This protocol details planned methods to conduct a systematic review to identify and appraise eligible studies and to use a network meta-analysis to synthesize available evidence to answer the following questions: in preclinical in vivo models of focal ischemic stroke, what are the relative benefits of competing therapies tested in combination with the gold standard treatment alteplase in (i) reducing cerebral infarction size, and (ii) improving neurobehavioural outcomes? Methods: We will search Ovid Medline and Embase for articles on the effects of combination therapies with alteplase. Controlled comparison studies of preclinical in vivo models of experimentally induced focal ischemia testing the efficacy of therapies with alteplase versus alteplase alone will be identified. Outcomes to be extracted include infarct size (primary outcome) and neurobehavioural measures. Risk of bias and construct validity will be assessed using tools appropriate for preclinical studies. Here we describe steps undertaken to perform preclinical network meta-analysis to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. This will be a novel use of this evidence synthesis approach in stroke medicine to assess pre-clinical therapeutics. Combining all evidence to simultaneously compare mutliple therapuetics tested preclinically may provide a rationale for the clinical translation of therapeutics for patients with ischemic stroke. Dissemination: Review findings will be submitted to a peer-reviewed journal and presented at relevant scientific meetings to promote knowledge transfer. Registration: PROSPERO number to be submitted following peer review.

    Research areas

  • stroke, preclinical, systematic review, network metaanalysis, network meta-analysis

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via F1000Research at Please refer to any applicable terms of use of the publisher.

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    Licence: CC BY


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