{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:04:56Z","timestamp":1783955096740,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100024157","name":"Neurelis","doi-asserted-by":"publisher","award":["K23NS135134"],"award-info":[{"award-number":["K23NS135134"]}],"id":[{"id":"10.13039\/100024157","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Appropriate endpoints for daily antiseizure medications may differ from those for intermittent, immediate\u2010use seizure medications (ISMs). The observed interval between seizure clusters over time (SEIzure interVAL [SEIVAL]) has been proposed as a novel effectiveness endpoint for ISMs. SEIVAL was initially identified pragmatically. This post hoc analysis evaluated how the study timeline and participant characteristics could impact the measurement of SEIVAL using data from an open\u2010label study of intermittent treatment with diazepam nasal spray.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This analysis includes data from a long\u2010term, phase 3 safety study of diazepam nasal spray, which enrolled patients aged 6\u201365\u2009years with epilepsy and seizure clusters (NCT02721069). Study timeline and participant characteristic choices were evaluated systematically to determine the impact on effect size, and thereby statistical power, using data regarding individual treated seizure clusters. In this strategy, the date of the first treated seizure cluster constituted day 1 of the baseline period; consecutive 70\u2010day periods were used for analysis. The change in SEIVAL for each patient was calculated using each measured SEIVAL for that patient in the primary outcome period (days 71\u2013140) minus that patient's mean SEIVAL in the baseline period (days 1\u201370) with mixed effects linear regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean SEIVAL increased from 13\u2009days at baseline (days 1\u201370) to 24\u2009days in the primary outcome period (days 71\u2013140,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001). SEIVAL lengthening was seen in adults, adolescents (ages 6\u201317\u2009years), and children (ages 6\u201312\u2009years), with further lengthening past 140\u2009days in adolescents and children. SEIVAL lengthened more in participants with &lt;1 SEIVAL per 2\u2009weeks at baseline than higher SEIVAL frequency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>This systematically planned analysis expands on and reinforces the previous pragmatic analysis that introduced the SEIVAL metric. The present analysis provides a novel framework for future studies of intermittently administered ISMs to treat seizure clusters such as diazepam nasal spray.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70222","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T12:15:21Z","timestamp":1775045721000},"page":"3432-3443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic statistical analysis of change in\n                    <scp>SEIzure interVAL<\/scp>\n                    with diazepam nasal spray supports this novel clinical endpoint for immediate\u2010use seizure medication"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5546-5951","authenticated-orcid":false,"given":"Wesley T.","family":"Kerr","sequence":"first","affiliation":[{"name":"Division of Epilepsy, Department of Neurology University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Biomedical Informatics University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0365-813X","authenticated-orcid":false,"given":"Katherine N.","family":"McFarlane","sequence":"additional","affiliation":[{"name":"Division of Epilepsy, Department of Neurology University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-1367","authenticated-orcid":false,"given":"Leock Y.","family":"Ngo","sequence":"additional","affiliation":[{"name":"Neurelis  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8788-0722","authenticated-orcid":false,"given":"Enrique","family":"Carrazana","sequence":"additional","affiliation":[{"name":"Neurelis  San Diego California USA"},{"name":"John A. Burns School of Medicine University of Hawaii  Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-0606","authenticated-orcid":false,"given":"Adrian L.","family":"Rabinowicz","sequence":"additional","affiliation":[{"name":"Neurelis  San Diego California USA"},{"name":"Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science Florida Atlantic University  Boca Raton Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12550"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101167.2009.02397.x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14596"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2022.2105207"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2021.106748"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000177"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108013"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17385"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2022.108811"},{"key":"e_1_2_13_11_1","volume-title":"VALTOCO\u00ae (diazepam nasal spray). 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