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Novel study design to assess the efficacy and tolerability of antiseizure medications for focal-onset seizures in infants and young children: A consensus document from the regulatory task force and the pediatric commission of the International League against Epilepsy (ILAE), in collaboration with the Pediatric Epilepsy Research Consortium (PERC).
Epilepsia Open 2019; 4(4):537-543EO

Abstract

High-quality placebo-controlled drug trials for focal-onset seizures in infants and children younger than 4 years have become increasingly difficult to perform because of eligibility constraints and onerous study designs. Traditional designs used in these populations require a high baseline seizure frequency, two hospitalizations for video-electroencephalography (video-EEG) monitoring, and willingness to accept potential exposure to placebo when the drugs to be tested are usually already available for off-label prescription. To address these constraints, the International League Against Epilepsy (ILAE) regulatory taskforce and the ILAE pediatric commission, in collaboration with the Pediatric Epilepsy Research Consortium (PERC), propose a novel trial design which involves seizure counting by caregivers based on previous video-EEG/video validation of specific seizure semiologies. We present a novel randomized placebo-controlled trial design intended to be used for studying new antiseizure medications (ASMs) for focal-onset seizures (FOS) in children aged one month to four years. This design uses "time to Nth seizure" as the primary outcome and incorporates a new element of variable baseline duration. This approach permits enrollment of infants with lower seizure burden, who might not have video-EEG-recorded seizures within 2-3 days of monitoring. Repeated hospitalizations for video-EEG recordings are avoided, and duration of baseline and exposure to placebo or ineffective treatment(s) are minimized. By broadening eligibility criteria, reducing risks from prolonged placebo exposure, and relying on validated recording of seizure counting by caregivers, clinical trials will be likely to be completed more efficiently than in the recent past.

Authors+Show Affiliations

Department of Pediatric Neurology AP-HP Robert-Debré University Hospital CRMR Epilepsies Rares Paris France. Université de Paris INSERM U1141 Paris France.NYU Langone School of Medicine New York NY USA.Division of Neurology Children's Hospital of Philadelphia (CHOP) Philadelphia PA USA. Departments of Neurology and Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA.Department of Pediatrics and Neurology University of Colorado Aurora CO USA.Department of Internal Medicine and Therapeutics Member of the ERN EpiCARE University of Pavia and IRCCS Mondino Foundation Pavia Italy.Department of Clinical Pediatric Epileptology and Functional Neurology Member of the ERN EpiCARE University Hospitals of Lyon (HCL) Lyon France.Global Biometrics and Data Management Pfizer Inc New York NY USA.Division of Pediatric Neurology Department of Pediatrics Michigan Medicine Ann Arbor MI USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31819909

Citation

Auvin, Stéphane, et al. "Novel Study Design to Assess the Efficacy and Tolerability of Antiseizure Medications for Focal-onset Seizures in Infants and Young Children: a Consensus Document From the Regulatory Task Force and the Pediatric Commission of the International League Against Epilepsy (ILAE), in Collaboration With the Pediatric Epilepsy Research Consortium (PERC)." Epilepsia Open, vol. 4, no. 4, 2019, pp. 537-543.
Auvin S, French J, Dlugos D, et al. Novel study design to assess the efficacy and tolerability of antiseizure medications for focal-onset seizures in infants and young children: A consensus document from the regulatory task force and the pediatric commission of the International League against Epilepsy (ILAE), in collaboration with the Pediatric Epilepsy Research Consortium (PERC). Epilepsia Open. 2019;4(4):537-543.
Auvin, S., French, J., Dlugos, D., Knupp, K. G., Perucca, E., Arzimanoglou, A., ... Shellhaas, R. A. (2019). Novel study design to assess the efficacy and tolerability of antiseizure medications for focal-onset seizures in infants and young children: A consensus document from the regulatory task force and the pediatric commission of the International League against Epilepsy (ILAE), in collaboration with the Pediatric Epilepsy Research Consortium (PERC). Epilepsia Open, 4(4), pp. 537-543. doi:10.1002/epi4.12356.
Auvin S, et al. Novel Study Design to Assess the Efficacy and Tolerability of Antiseizure Medications for Focal-onset Seizures in Infants and Young Children: a Consensus Document From the Regulatory Task Force and the Pediatric Commission of the International League Against Epilepsy (ILAE), in Collaboration With the Pediatric Epilepsy Research Consortium (PERC). Epilepsia Open. 2019;4(4):537-543. PubMed PMID: 31819909.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel study design to assess the efficacy and tolerability of antiseizure medications for focal-onset seizures in infants and young children: A consensus document from the regulatory task force and the pediatric commission of the International League against Epilepsy (ILAE), in collaboration with the Pediatric Epilepsy Research Consortium (PERC). AU - Auvin,Stéphane, AU - French,Jacqueline, AU - Dlugos,Denis, AU - Knupp,Kelly G, AU - Perucca,Emilio, AU - Arzimanoglou,Alexis, AU - Whalen,Ed, AU - Shellhaas,Renée A, Y1 - 2019/09/04/ PY - 2019/06/23/received PY - 2019/08/01/revised PY - 2019/08/01/accepted PY - 2019/12/11/entrez PY - 2019/12/11/pubmed PY - 2019/12/11/medline KW - antiseizure drugs KW - children KW - clinical trials KW - drug development KW - infants SP - 537 EP - 543 JF - Epilepsia open JO - Epilepsia Open VL - 4 IS - 4 N2 - High-quality placebo-controlled drug trials for focal-onset seizures in infants and children younger than 4 years have become increasingly difficult to perform because of eligibility constraints and onerous study designs. Traditional designs used in these populations require a high baseline seizure frequency, two hospitalizations for video-electroencephalography (video-EEG) monitoring, and willingness to accept potential exposure to placebo when the drugs to be tested are usually already available for off-label prescription. To address these constraints, the International League Against Epilepsy (ILAE) regulatory taskforce and the ILAE pediatric commission, in collaboration with the Pediatric Epilepsy Research Consortium (PERC), propose a novel trial design which involves seizure counting by caregivers based on previous video-EEG/video validation of specific seizure semiologies. We present a novel randomized placebo-controlled trial design intended to be used for studying new antiseizure medications (ASMs) for focal-onset seizures (FOS) in children aged one month to four years. This design uses "time to Nth seizure" as the primary outcome and incorporates a new element of variable baseline duration. This approach permits enrollment of infants with lower seizure burden, who might not have video-EEG-recorded seizures within 2-3 days of monitoring. Repeated hospitalizations for video-EEG recordings are avoided, and duration of baseline and exposure to placebo or ineffective treatment(s) are minimized. By broadening eligibility criteria, reducing risks from prolonged placebo exposure, and relying on validated recording of seizure counting by caregivers, clinical trials will be likely to be completed more efficiently than in the recent past. SN - 2470-9239 UR - https://www.unboundmedicine.com/medline/citation/31819909/Novel_study_design_to_assess_the_efficacy_and_tolerability_of_antiseizure_medications_for_focal-onset_seizures_in_infants_and_young_children:_A_consensus_document_from_the_regulatory_task_force_and_the_pediatric_commission_of_the_International_League_against_Epilepsy_(ILAE),_in_collaboration_with_the_Pediatric_Epilepsy_Research_Consortium_(PERC) L2 - https://doi.org/10.1002/epi4.12356 DB - PRIME DP - Unbound Medicine ER -