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The Stroke Preclinical Assessment Network Multi-Laboratory Model of Thromboembolic Stroke with Thrombolysis: TE-MCAo
Published on: December 19, 2025
Emulating multicentre clinical stroke trials: a new paradigm for studying novel interventions in experimental models
P M W Bath1, M R Macleod, A R Green
1Stroke Trials Unit, Division of Stroke Medicine, City Hospital Campus, University of Nottingham, Nottingham, UK. philip.bath@nottingham.ac.uk
Abstract:
The recent meta-analysis of NXY-059 in experimental stroke models using individual animal data found the drug to be an effective neuroprotective agent. However, the failure of translation of both this compound and many others from preclinical studies to the clinic indicates that new approaches must be used in drug discovery so that animal models become more reflective of the clinical situation, and studies using animal models of stroke mimic the design of studies performed in humans, as far as possible. In this review, we suggest that a fundamental paradigm shift is needed away from performing preclinical studies in individual laboratories to performing them in an organised group of independent laboratories. Studies should be run by a steering committee and should be supported by a coordinating centre, external data monitoring committee and outcome adjudication committee. This structure will mimic the practice of multicentre clinical trials. By doing so, future studies will minimise potential sources of bias including randomisation, concealment of allocation, blinding of surgery and outcome assessment and ensure publication of all data. It is likely that individual studies will involve increased heterogeneity and therefore will need to be larger. However, regular independent monitoring of data will allow development of interventions to be ceased immediately if neutral or negative data are obtained. The additional costs involved should be seen as reasonable when compared with the resources that would have been expended in running a clinical trial that subsequently proved negative.
Insights
New approaches are needed for drug discovery in stroke research. A paradigm shift towards multicenter preclinical trials, mimicking clinical studies, can improve translation from animal models to human therapies.
Area of Science:
- Neuroscience
- Pharmacology
- Translational Medicine
Background:
- NXY-059 showed neuroprotection in experimental stroke models.
- Many preclinical stroke drug candidates fail to translate to clinical success.
- Current preclinical models may not accurately reflect clinical stroke scenarios.
Purpose of the Study:
- To propose a new paradigm for preclinical stroke research.
- To enhance the translational validity of animal studies.
- To minimize bias and improve reliability in drug discovery.
Main Methods:
- Shift from single-laboratory studies to organized, independent, multicenter preclinical trials.
- Implement structures mirroring multicenter clinical trials: steering committees, coordinating centers, data monitoring, and outcome adjudication.
- Standardize protocols for randomization, allocation concealment, blinding, and outcome assessment.
Main Results:
- Multicenter approach minimizes potential sources of bias.
- Ensures publication of all data, including negative results.
- Allows for early cessation of ineffective interventions based on independent data monitoring.
Conclusions:
- A paradigm shift to multicenter preclinical trials is essential for effective stroke drug discovery.
- This approach enhances the reliability and translatability of preclinical findings.
- Mimicking clinical trial design in preclinical studies will improve the success rate of new stroke therapies.