ReviewStroke2023
Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial.
Review in Stroke, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Role of histone deacetylases and sirtuins in the ischaemic stroke: a systematic review and meta-analysis of animal studies.Stroke and vascular neurology · 2026Pooled it
- A Ubiquitous Blood Flow Biomarker to Calculate Hypoxic-Ischemic Depolarization Latency in a Mouse Model of Focal Ischemic Stroke: Insight Into Metabolic and Electrophysiological Resilience.Translational stroke research · 2026Article
- Review
- Methods for randomized, blinded, controlled evaluation of putative disease interventions in multilaboratory, preclinical assessment networks.Lab animal · 2026Article
- Feasibility of a Multi-Laboratory Model of Middle Cerebral Artery Thromboembolic Stroke with Thrombolysis: TE-MCAo.Translational stroke research · 2026Article
- Review
- The Stroke Preclinical Assessment Network Multi-laboratory Model of Thromboembolic Stroke with Thrombolysis: TE-MCAo.Journal of visualized experiments : JoVE · 2025Article
- Multicenter Translational Trial of Remote Ischemic Conditioning in Acute Ischemic Stroke (TRICS BASIC).Stroke · 2025Article
- Metabolic reprogramming in ischemic stroke: when glycolytic overdrive meets lipid storm.Cell death & disease · 2025Review
- Multicenter Stroke Preclinical Assessment Network Analysis of Cardiovascular Risk Factor Subgroups Treated With the Poly(ADP-Ribose) Polymerase Inhibitor Veliparib.Journal of the American Heart Association · 2025Article
- Article
- Angiotensin II Type 2 Receptor Agonism Alleviates Progressive Post-stroke Cognitive Impairment in Aged Spontaneously Hypertensive Rats.Translational stroke research · 2025Article
- Examination of Inter-α Inhibitor Proteins in Permanent and Transient Focal Ischemia.Journal of the American Heart Association · 2025Article
- Periorbital Placement of a Laser Doppler Probe for Cerebral Blood Flow Monitoring Prior to Middle Cerebral Artery Occlusion in Rodent Models.Journal of visualized experiments : JoVE · 2024Article
- Biological and Procedural Predictors of Outcome in the Stroke Preclinical Assessment Network (SPAN) Trial.Circulation research · 2024Article
- Immune-Neurovascular Interactions in Experimental Perinatal and Childhood Arterial Ischemic Stroke.Stroke · 2024Review
- CNS Drug Delivery in Stroke: Improving Therapeutic Translation From the Bench to the Bedside.Stroke · 2024Review
- Evolving Clinical-Translational Investigations of Cerebroprotection in Ischemic Stroke.Journal of clinical medicine · 2023Review
- Preclinical models of middle cerebral artery occlusion: new imaging approaches to a classic technique.Frontiers in neurology · 2023Review
- A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia.Cerebral circulation - cognition and behavior · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
The Stroke Preclinical Assessment Network (SPAN) is a multicenter preclinical trial platform using rodent models of transient focal cerebral ischemia to address translational failure in experimental stroke. In addition to centralized randomization and blinding and large samples, SPAN aimed to introduce heterogeneity to simulate the heterogeneity embodied in clinical trials for robust conclusions. Here, we report the heterogeneity introduced by allowing the 6 SPAN laboratories to vary most of the biological and experimental model variables and the impact of this heterogeneity on middle cerebral artery occlusion (MCAo) performance. We included the modified intention-to-treat population of the control mouse cohort of the first SPAN trial (n=421) and examined the biological and procedural independent variables and their covariance. We then determined their impact on the dependent variables cerebral blood flow drop during MCAo, time to achieve MCAo, and total anesthesia duration using multivariable analyses. We found heterogeneity in biological and procedural independent variables introduced mainly by the site. Consequently, all dependent variables also showed heterogeneity among the sites. Multivariable analyses with the site as a random effect variable revealed filament choice as an independent predictor of cerebral blood flow drop after MCAo. Comorbidity, sex, use of laser Doppler flow to monitor cerebral blood flow, days after trial onset, and maintaining anesthesia throughout the MCAo emerged as independent predictors of time to MCAo. Total anesthesia duration was predicted by most independent variables. We present with high granularity the heterogeneity introduced by the biological and model selections by the testing sites in the first trial of cerebroprotection in rodent transient filament MCAo by SPAN. Rather than trying to homogenize all variables across all sites, we embraced the heterogeneity to better approximate clinical trials. Awareness of the heterogeneity, its sources, and how it impacts the study performance may further improve the study design and statistical modeling for future multicenter preclinical trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.