The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results.

Area of Science:

• Neuroscience
• Translational Medicine
• Experimental Design

Background:

• Cerebral ischemia and reperfusion cause neurological disability, yet no stroke treatments have translated from preclinical studies.
• Prior translational failures are linked to insufficient scientific rigor in preclinical assessments, including bias and lack of replication.
• The Stroke Preclinical Assessment Network (SPAN) was established to address these critical issues in stroke research.

Purpose of the Study:

• To test the hypothesis that rigorous preclinical assessment can reduce or eliminate bias in selecting stroke treatments for clinical evaluation.
• To implement a state-of-the-art experimental design for reliable preclinical assessment of candidate stroke therapies.
• To establish a feasible and practical multilaboratory framework for enhancing the rigor of preclinical stroke research.

Main Methods:

• SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial employing a multi-arm multi-stage protocol.
• Standardized middle cerebral artery occlusion surgery was performed across 6 independent laboratories.
• Stage 1 enrolled 913 mice, implementing procedural standardization, treatment masking, randomization, and blinded outcome assessment.

Main Results:

• Excellent protocol adherence, data completion, and low subject loss were achieved across all participating laboratories.
• SPAN stage 1 successfully implemented key elements of experimental rigor, including randomization and blinded assessment, effectively reducing bias.
• The findings demonstrate the feasibility and practicality of a large-scale, multilaboratory effort to enhance preclinical research standards.

Conclusions:

• Rigorous preclinical assessment is a feasible and practical approach to mitigate bias in selecting stroke treatments.
• The SPAN framework provides a robust model for improving the reliability of preclinical research, increasing the likelihood of successful clinical translation.
• Future SPAN stages will incorporate aged animals and those with comorbid conditions to further enhance translational relevance for stroke clinical trials.