{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:16:00Z","timestamp":1783433760533,"version":"3.54.6"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["165943"],"award-info":[{"award-number":["165943"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple sclerosis (MS) is commonly stratified into activity\u2010based subgroups to inform treatment decisions and health technology assessments (HTAs). However, the terminology and criteria used to define these subgroups, particularly \u2018active\u2019, \u2018highly active\u2019 and \u2018rapidly evolving severe\u2019 (RES) disease, are inconsistent across clinical trials and regulatory guidance, leading to ambiguity in practice and restricted treatment access. Our objectives were to review how activity\u2010based subgroups in MS are defined across NICE technology appraisals (TAs) and the randomised controlled trials (RCTs) that inform them, and to propose a preliminary framework for standardised terminology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified and reviewed NICE TAs of disease\u2010modifying therapies (DMTs) for MS and the RCTs included in those appraisals. We extracted and compared definitions used to characterise activity\u2010based MS subgroups, and classified them by key components such as relapse history, MRI findings and treatment status. We summarised our findings and highlighted points of consensus and controversy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Definitions varied widely, especially for \u2018highly active\u2019 RRMS and active SPMS. While most TAs used consistent criteria for \u2018active\u2019 and \u2018RES\u2019 RRMS disease, definitions in RCTs were heterogeneous. We identified frequent overlaps in terminology and proposed a simplified framework comprising three distinct but overlapping subgroups for RMS: active RRMS\/RRMS, highly active RRMS (HARRMS) and rapidly evolving severe RRMS (RES\u2010RRMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Standardised definitions are urgently needed to improve evidence synthesis, inform regulatory guidance and ensure equitable treatment access. We propose a formal consensus process to consolidate this framework for use in future research, HTAs and treatment pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70663","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T13:00:03Z","timestamp":1781096403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining Activity\u2010Based Subgroups in Multiple Sclerosis: A Review and Framework Proposal"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8883-0167","authenticated-orcid":false,"given":"Catalina","family":"Lopez Manzano","sequence":"first","affiliation":[{"name":"Bristol Technology Assessment Group (TAG), Population Health Sciences, Bristol Medical School University of Bristol  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9851-4426","authenticated-orcid":false,"given":"Claire M.","family":"Rice","sequence":"additional","affiliation":[{"name":"School of Psychology and Neuroscience University of Bristol  Bristol UK"},{"name":"Department of Neurology North Bristol NHS Trust  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Tallantyre","sequence":"additional","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neurosciences, School of Medicine Cardiff University  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-1783","authenticated-orcid":false,"given":"Chris","family":"Cooper","sequence":"additional","affiliation":[{"name":"Bristol Technology Assessment Group (TAG), Population Health Sciences, Bristol Medical School University of Bristol  Bristol 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