Evidence map›Paper›PMID 38056191›Full record

ArticleEpilepsy research2024

Successful harmonization in EpiBioS4Rx biomarker study on post-traumatic epilepsy paves the way towards powered preclinical multicenter studies.

Xavier Ekolle Ndode-Ekane, Idrish Ali, Cesar E Santana-Gomez, Pablo M Casillas-Espinosa, Pedro Andrade, Gregory Smith, Tomi Paananen, Eppu Manninen, Riikka Immonen, Noora Puhakka and 15 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsy research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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  8. New epilepsy therapies in development.Nature reviews. Drug discovery · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 5 institutions in 3 countries.

Xavier Ekolle Ndode-EkaneA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Idrish AliDepartment of Neuroscience, Monash University, Australia; Department of Neurology, Alfred Health, Australia; Department of Medicine, The University of Melbourne, Australia.
Cesar E Santana-GomezDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Pablo M Casillas-EspinosaDepartment of Neuroscience, Monash University, Australia; Department of Neurology, Alfred Health, Australia; Department of Medicine, The University of Melbourne, Australia.
Pedro AndradeA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Gregory SmithDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Tomi PaananenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Eppu ManninenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Riikka ImmonenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Noora PuhakkaA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Robert CiszekA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Elina HämäläinenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Rhys D BradyDepartment of Neuroscience, Monash University, Australia.
Juliana SilvaDepartment of Neuroscience, Monash University, Australia.
Emma BraineDepartment of Neuroscience, Monash University, Australia.
Matthew R HudsonDepartment of Neuroscience, Monash University, Australia; Department of Neurology, Alfred Health, Australia.
Glenn YamakawaDepartment of Neuroscience, Monash University, Australia.
Nigel C JonesDepartment of Neuroscience, Monash University, Australia; Department of Neurology, Alfred Health, Australia; Department of Medicine, The University of Melbourne, Australia.
Sandy R ShultzDepartment of Neuroscience, Monash University, Australia; Department of Neurology, Alfred Health, Australia; Department of Medicine, The University of Melbourne, Australia.
David WrightDepartment of Neuroscience, Monash University, Australia; Department of Neurology, Alfred Health, Australia; Department of Medicine, The University of Melbourne, Australia.
Neil HarrisDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Olli GröhnA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Richard J StabaDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Terence J O'BrienDepartment of Neuroscience, Monash University, Australia; Department of Neurology, Alfred Health, Australia; Department of Medicine, The University of Melbourne, Australia.
Asla PitkänenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland. Electronic address: asla.pitkanen@uef.fi.
University of Eastern Finland · FIMonash University · AUUniversity of California, Los Angeles · USAlfred Health · AUUniversity of Melbourne · AU

Funding

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) Public Engagement CoreU54NS100064 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ENGEL, JEROME NONE, GALANOPOULOU, ARISTEA S · 2017 to 2021
$21.7M
NINDS NIH HHS U54 NS100064
6 · The paper itself

Abstract

objectiveProject 1 of the Preclinical Multicenter Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) consortium aims to identify preclinical biomarkers for antiepileptogenic therapies following traumatic brain injury (TBI). The international participating centers in Finland, Australia, and the United States have made a concerted effort to ensure protocol harmonization. Here, we evaluate the success of harmonization process by assessing the timing, coverage, and performance between the study sites.

methodWe collected data on animal housing conditions, lateral fluid-percussion injury model production, postoperative care, mortality, post-TBI physiological monitoring, timing of blood sampling and quality, MR imaging timing and protocols, and duration of video-electroencephalography (EEG) follow-up using common data elements. Learning effect in harmonization was assessed by comparing procedural accuracy between the early and late stages of the project.

resultsThe animal housing conditions were comparable between the study sites but the postoperative care procedures varied. Impact pressure, duration of apnea, righting reflex, and acute mortality differed between the study sites (p < 0.001). The severity of TBI on D2 post TBI assessed using the composite neuroscore test was similar between the sites, but recovery of acute somato-motor deficits varied (p < 0.001). A total of 99% of rats included in the final cohort in UEF, 100% in Monash, and 79% in UCLA had blood samples taken at all time points. The timing of sampling differed on day (D)2 (p < 0.05) but not D9 (p > 0.05). Plasma quality was poor in 4% of the samples in UEF, 1% in Monash and 14% in UCLA. More than 97% of the final cohort were MR imaged at all timepoints in all study sites. The timing of imaging did not differ on D2 and D9 (p > 0.05), but varied at D30, 5 months, and ex vivo timepoints (p < 0.001). The percentage of rats that completed the monthly high-density video-EEG follow-up and the duration of video-EEG recording on the 7th post-injury month used for seizure detection for diagnosis of post-traumatic epilepsy differed between the sites (p < 0.001), yet the prevalence of PTE (UEF 21%, Monash 22%, UCLA 23%) was comparable between the sites (p > 0.05). A decrease in acute mortality and increase in plasma quality across time reflected a learning effect in the TBI production and blood sampling protocols. SIGNIFICANCE: Our study is the first demonstration of the feasibility of protocol harmonization for performing powered preclinical multi-center trials for biomarker and therapy discovery of post-traumatic epilepsy.

Indexed as

Brain Injuries, TraumaticEpilepsyEpilepsy, Post-TraumaticAnimalsBiomarkersDisease Models, AnimalMulticenter Studies as TopicRatsSeizuresBiomarkersCommon data elementEpileptogenesisLateral fluid-percussion injuryMagneticPlasma samplingResonance imagingTraumatic brain injuryVideoelectroencephalogram

Identifiers

PMID38056191
PMCPMC12301999
OpenAlexW4388968552

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.