Preface - Practical and theoretical considerations for performing a multi-center preclinical biomarker discovery study of post-traumatic epileptogenesis: lessons learned from the EpiBioS4Rx consortium☆
Section snippets
Towards preclinical randomized controlled multicenter trials for biomarker discovery – EpiBioS4Rx is carrying the torch
Several research areas, particularly stroke, spinal cord injury and TBI, have over the recent years raised concerns regarding the “reproducibility crisis” in preclinical therapy discovery studies (DeWitt et al., 2018; Dirnagl et al., 2013; Steward et al., 2012). These concerns have kindled discussion regarding the need for preclinical randomized controlled multicenter trials (pRCTs) to increase animal numbers and methodological rigor, and consequently achieve statistical power and experimental
Setting-up a multicenter preclinical biomarker discovery study - lessons learned
The planning, conduction, and analysis of harmonization of a preclinical multicenter study can be divided into three phases summarized in Fig. 1.
Conclusions
So far, there are two reports available from preclinical multicenter trials. In TBI, the Operation Brain Trauma Therapy study investigated various therapies to improve post-TBI recovery (Kochanek et al., 2011). In stoke, a large pRCT investigated the efficacy of anti-CD49d treatment for acute brain ischemia (Llovera et al., 2015). These studies, however, did not report the use of CDEs/CRFs, and no detailed analyses of the harmonization procedures were presented. The six articles in this virtual
Acknowledgement
This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Centers without Walls [grant number U54 NS100064].
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Cited by (8)
Pediatric traumatic brain injury and a subsequent transient immune challenge independently influenced chronic outcomes in male mice
2022, Brain, Behavior, and ImmunityCitation Excerpt :However, LPS had no effect on seizure susceptibility. Future studies to address the question of how early life combinatorial challenges impact epileptogenesis may need to take advantage of multi-center preclinical consortium to ensure enough animals are studied to ensure appropriate statistical power for the low and variable incidence of spontaneous seizures in rodent models (Casillas-Espinosa et al., 2019a; Pitkänen et al., 2019; O'Brien et al., 2013). We next examined chronic tissue atrophy and evidence of a persistent neuroinflammatory response after pediatric TBI and acute post-injury LPS.
Biomarkers for posttraumatic epilepsy
2021, Epilepsy and BehaviorCitation Excerpt :To overcome these challenges, sample collection and analysis protocols must be rigorously standardized between laboratories [185]. The Framework 7-funded EpiTarget (www.epitarget.eu) and NINDS-funded Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx)(www.epibios.loni.usc.edu) consortia have made the first attempt to harmonize preclinical procedures for discovery of molecular, electrophysiologic, and MRI biomarkers for PTEgenesis [185,186]. As an example, the consortia have applied standardized blood sampling [187,188] and MRI protocols [189].
The potential and challenge of multicenter preclinical research
2019, Epilepsy Research
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This article is part of a virtual special issue ‘Discovery of diagnostic biomarkers for post-traumatic epileptogenesis – an interim analysis of procedures in preclinical multicenter trial EpiBios4Rx’.