Systematic Review and Meta-analysis of Methodological Quality in In Vivo Animal Studies of Subarachnoid Hemorrhage

As a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists and guidelines were developed over the past decades. This systematic review assesses the overall methodological quality of preclinical SAH research. An electronic search for preclinical studies on SAH revealed 3415 potential articles. Of these, 765 original research papers conducted in vivo in mice, rats, rabbits, cats, dogs, pigs, goats, and non-human primates with a focus on brain damage related to delayed cerebral vasospasm and early brain injury met the inclusion criteria. We found methodological shortcomings still to prevail in preclinical SAH research. In addition, basic animal characteristics were typically well described but important technical parameters of SAH induction were often underreported. None of the species, models, or techniques used in preclinical SAH research was methodologically superior to the others. Methodological quality of preclinical SAH research was independent of the number of citations or impact factor of a publication. Consequently, we suggest the SAH research community should consider strategies to improve preclinical research quality in their field, such as public platforms to (pre)register preclinical experiments, consequent support of open science policies, stricter editorial (and reviewer) control of (pre)existing guidelines, and increased efforts in education and training of good laboratory practice for the next generation of researchers.