Elsevier

Epilepsy Research

Volume 156, October 2019, 106080
Epilepsy Research

Preface - Practical and theoretical considerations for performing a multi-center preclinical biomarker discovery study of post-traumatic epileptogenesis: lessons learned from the EpiBioS4Rx consortium

https://doi.org/10.1016/j.eplepsyres.2019.01.007Get rights and content

Highlights

  • EpiBioS4Rx: the 1st preclinical multicenter study for epilepsy biomarker discovery.

  • We present an interim analysis of success of methodological harmonization.

  • We propose a 3-stage procedure for multicenter studies.

Abstract

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is a NINDS funded Center-Without-Walls international study aimed at preventing epileptogenesis after traumatic brain injury (TBI). One objective of EpiBioS4Rx relates to preclinical biomarker discovery for post-traumatic epilepsy. In order to perform a statistically appropriately powered biomarker discovery study, EpiBioS4Rx has made a rigorous attempt to harmonize the preclinical procedures performed at the three EpiBioS4Rx centers, located in Finland, Australia, and the USA. Moreover, we have also performed a rigorous interim analysis of the success of procedural harmonization, which is reported in this virtual special issue. The analysis included harmonization of the production of animal model, blood sampling, electroencephalogram analyses (seizures, high-frequency oscillations) and magnetic resonance imaging analysis. Based on lessons learned, we propose a 3-stage protocol to facilitate the success of preclinical multicenter studies: preparation ⇨ testing ⇨ multicenter study. The need of funding for preparation and testing phases, which precede the actual multicenter study and are necessary for its success, should be taken into account in the design of funding schemes

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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    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’.

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