{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:46:13Z","timestamp":1792107973761,"version":"4.4.0"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The International Neonatal Consortium Seizure Working Group of the Critical Path Institute provides an update to the original recommendations for design of clinical trials to treat neonatal seizures based on recent experiences from several trials and developments in the field. Although there aren\u2019t sufficient new data to inform definitions of optimal efficacy endpoints, the Working Group recommended inclusion of alternate measures of seizure burden reduction as secondary or exploratory endpoints, to elucidate clinically meaningful efficacy endpoints for future trials. It was recommended to include additional key covariates, such as timing of seizure onset\/cessation, randomization, and ASM administration. There are new recommendations regarding potential for unmasked or single-masked trials, and reporting of concomitant medications and adverse events, and genetic testing. Importantly, specific recommendations were added regarding improved strategies for recruitment and consent, including the use of novel technologies and the involvement of patient advocacy groups. Recommendations regarding trial infrastructure and operational feasibility were included to facilitate trial initiation and conduct, given the many logistical challenges of conducting neonatal seizure treatment trials. Finally, the recommendations consider accommodations for local or national regulations and resources, to ensure that trials are conducted as appropriate to the setting in which the patients are treated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This review provides an update to the initial recommendations for neonatal seizure treatment trial design, with recommendations regarding: (1) exploratory endpoints to inform future trials, (2) additional key covariates to include, (3) considerations regarding masking of investigators, (3) inclusion of concomitant medications and adverse events, (4) genetic testing, (5) strategies for recruitment and consent, and (6) infrastructure and operational feasibility.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04735-1","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:03:12Z","timestamp":1768978992000},"page":"1020-1027","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Updated recommendations for the design of therapeutic trials for neonatal seizures"],"prefix":"10.1038","volume":"100","author":[{"given":"Janet S.","family":"Soul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cia","family":"Sharpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy","family":"Pilon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronit M.","family":"Pressler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilee C.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahimeda","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Auvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Barry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Denne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah C.","family":"Glass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes V.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Marlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Rabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanwaljit","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Hovinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the International Neonatal Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"4735_CR1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jpeds.2016.03.035","volume":"174","author":"HC Glass","year":"2016","unstructured":"Glass, H. 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He has received personal fees for lectures or advice from: Angelini, Biocodex, Eisai, Encoded, GRIN Therapeutics, Jazz Pharmaceuticals, Longboard, Neuraxpharm, Nutricia, Orion, Proveca, Servier, Stoke, UCB Pharma, Xenon. He has been investigator for: Eisai, Marinus, Proveca, Takeda, UCB Pharma. Cia Sharpe has done consulting work for SunPharma. Sonya Wang currently has grant funding through NIH\/NIMH and FDA. Hannah Glass has had NIH\/NINDS grants, served as Medicolegal expert witness, Spouse holds shares in ELEMENO Health. Janet Soul has received research funding from NIH\/NINDS grants and royalties for Peer review for UpToDate. Ronit M. Pressler is an associate editor for Epilepsia-Open; acts as an Investigator for studies with UCB Pharma; has received honoraria from Longboard, Natus, Kephala, Autifony, and UCB Pharma for services on advisory bords, teaching or consultancy work; is supported by the National Institute of Health Research (NIHR) Biomedical Research Centre at Great Ormond Street Hospital, Evelyn Trust, Cambridge Biomedical Research Centre, and NIHR. The authors (BP, AVK, NM, CAH, HR, CB, KS, SD, MCA) declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The opinions expressed in this article are those of the authors and should not be interpreted as the position of the UK MHRA, U.S. Food and Drug Administration, National Institutes of Health, or the Department of Health and Human Services.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}