Procedural and Methodological Quality in Preclinical Stroke Research–A Cohort Analysis of the Rat MCAO Model Comparing Periods Before and After the Publication of STAIR/ARRIVE

Abstract

The translation of preclinical stroke research into successful human clinical trials remains a challenging task. The first Stroke Therapy Academic Industry Roundtable (STAIR) recommendations for preclinical research and several other guidelines were published to address these challenges. Most guidelines recommend the use of physiological monitoring to detect the occurrence of undesired pathologies such as subarachnoid hemorrhage and to limit the variability of the infarct volume and–therefore-homogenize the experimental result for complete reporting particularly with respect to transparency and methodological rigor. From the years 2009 and 2019, 100 published articles each using a rat stroke model were analyzed to quantify parameters related to anesthesia, physiological monitoring, stroke model type, ischemia verification, and overall study quality over time. No significant difference in the frequency of cerebral blood flow (CBF) measurements over time (28/34% for 2009/2019) was found. Notably, significantly fewer studies reported temperature, blood pressure, and blood gas monitoring data in 2019 compared to 2009. On the other hand, an increase in general study quality parameters (e.g., randomization, reporting of approval) was seen. In conclusion, the frequency of periinterventional monitoring has decreased over time. Some general methodological quality aspects, however, partially have increased. CBF measurement–the gold standard for ischemia verification-was applied rarely. Despite the growing recognition of current guidelines such as STAIR and ARRIVE (both widely approved in 2019) reporting, methods and procedures mostly do not follow these guidelines. These deficits may contribute to the translational failure of preclinical stroke research in search for neuroprotective therapies.