{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:59:25Z","timestamp":1793501965892,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001722","name":"Koninklijke Nederlandse Akademie van Wetenschappen","doi-asserted-by":"publisher","award":["KNAWWF\/2537\/TMF478"],"award-info":[{"award-number":["KNAWWF\/2537\/TMF478"]}],"id":[{"id":"10.13039\/501100001722","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The NeuroPace responsive neurostimulation (RNS) System effectively treats focal drug\u2010resistant epilepsy (DRE) in adults but lacks pediatric regulatory approval. Despite effective off\u2010label pediatric use, systemic device\u2010trial challenges have impeded label expansion. The prospective RESPONSE Study (NCT04839601), evaluating RNS in children with focal DRE, terminated prematurely after enrolling nine of 200 planned participants. We aimed to identify barriers to pediatric device\u2010trial participation and evaluate whether anticipated ethical concerns about insurance\u2010based access disparities materialized in practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a mixed\u2010methods study: a multi\u2010site cross\u2010sectional survey of barriers to RESPONSE participation, and a retrospective single\u2010site case study at Massachusetts General Hospital (MGH) analyzing insurance distribution against state benchmarks in 96 RNS patients (73 adults and 23 pediatric), with denial rates and time to first reimbursement in a 62\u2010patient subset (2020\u20132025).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Survey respondents comprised 8 of 9 RESPONSE sites plus MGH (which declined): 2 active, 6 withdrawn, and 1 declined. Study\u2010design and enrolment feasibility were the dominant barriers (89%), followed by financial (44%), resource (33%), ethical (22%), and regulatory concerns (11%). The narrow eligible population reflected a mismatch between regulatory\u2010aligned criteria (\u2264\u20092 seizure\u2010onset zones; exclusion of generalized or multifocal epilepsy; ages 12\u201317) and the heterogeneous presentations of real\u2010world pediatric DRE, limiting recruitment. Insurance distributions did not differ from statewide benchmarks (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.13) or between pre\u2010 and post\u2010evaluation periods (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.15). Denial occurred in 2\/26 off\u2010label pediatric (7.7%) and 1\/36 focal adult (2.8%) RNS indications, all upheld on appeal and resolved by institutional subsidy; time to reimbursement did not differ (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.31).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The RESPONSE Study's premature termination reflected systemic barriers to pediatric device trials rather than isolated site failures. Anticipated insurance\u2010based access disparities did not materialize locally. Advancing pediatric neuromodulation will require practice\u2010aligned protocol design, alternative evidence pathways including registry\u2010based real\u2010world evidence, and leadership from well\u2010resourced centers in collaborative evidence generation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70388","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:35:51Z","timestamp":1789054551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical trial barriers in neurostimulation for pediatric drug\u2010resistant epilepsy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7306-211X","authenticated-orcid":false,"given":"Mira C.","family":"Hasner","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Neurosurgery Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Neurosurgery Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Cell and Chemical Biology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-9501","authenticated-orcid":false,"given":"Faith C.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Neurosurgery Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel D.","family":"Sisterson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Neurosurgery Harvard Medical School  Boston Massachusetts 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