Project 467208

Stroke is the second leading cause of death worldwide and the third-leading cause of death and disability combined, with more than six and a half million deaths and 143 million experiencing new permanent disability annually. There are limited interventions to treat stroke, which few patients are eligible to receive. Given the burden of stroke, and the limitation in scope of who can receive treatment and limited efficacy for those that do, a multitude of therapies are being tested preclinically in animal models. However, it is difficult to identify the most promising therapeutic candidates for translation from animal to human studies due to the lack of efficacy comparison of all treatment options. To address this issue, a network meta-analysis (NMA) can be beneficial since this method compares multiple therapies directly and indirectly in a single analysis. This means that even if two therapies have never been directly compared in an experiment, the NMA can estimate how each would fare based on indirect comparisons. I will use the NMA to evaluate a large number of tested preclinical stroke therapeutics. In addition, I will systematically search databases to identify preclinical animal stroke experiments that tested the efficacy of therapies in combination with the gold-standard therapy, alteplase, compared to alteplase alone. The primary outcome of interest is infarct volume, which is related to the severity of disability following stroke. Multiple stakeholders will aid in the final stages of the review to help with interpretation and dissemination of the review findings. An NMAs unique ability to compare multiple interventions at a time has great potential to identify therapies that hold the greatest promise for further research development.