{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:21:42Z","timestamp":1788531702719,"version":"build-2803163510"},"reference-count":26,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["2026836, 2033165"],"award-info":[{"award-number":["2026836, 2033165"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001036","name":"Australian Rotary Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001036","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000924","name":"MS Australia","doi-asserted-by":"crossref","award":["21-2-065, 23-PDF-143"],"award-info":[{"award-number":["21-2-065, 23-PDF-143"]}],"id":[{"id":"10.13039\/501100000924","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Left-truncation is an unrecorded interval between multiple sclerosis (MS) onset and initial data in observational studies. This delay may bias estimates of disease-modifying therapy (DMT) effectiveness, especially when determined by patient or disease characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To examine whether causal effect estimates of DMTs over the full disease course can be reliably derived from left-truncated registry data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We analysed data from MSBase (144 centres, 41 countries) to assess the impact of left-truncation on causal treatment effect estimates. Cox marginal structural models (MSMs) estimated hazard ratios (HRs) for relapses, disability worsening and improvement, considering left-truncation at random and not-at-random. Fixed-time truncation and multivariable adjustment were applied to remediate bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The study included 5588 patients tracked from true MS onset. The null model, without left-truncation, estimated the DMT effect on relapse risk (HR\u2009=\u20090.64; 95% confidence interval (CI) = 0.54\u20130.77). Left-truncation inflated this estimate. Shorter random truncation (1\u2009year) produced greater bias (HR\u2009=\u20090.34), decreasing with longer durations (3-year HR\u2009=\u20090.48). Truncation not-at-random biased relapse estimates (HR\u2009=\u20090.37). Disability outcomes were less sensitive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>MSMs can reliably estimate DMT effectiveness in left-truncated MS registry data, although accuracy depends on truncation mechanism and duration. Both random and not-at-random truncation impact relapse estimates. Disability outcomes appear less sensitive. Fixed-time truncation and covariate adjustment mitigated bias.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261459943","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:08:02Z","timestamp":1784650082000},"page":"1052-1068","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal effects of multiple sclerosis therapies in left-truncated registry data"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3792-4130","authenticated-orcid":false,"given":"Dagmawi Chilot","family":"Haile","sequence":"first","affiliation":[{"name":"Clinical Outcomes Research Unit, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia; Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahima","family":"Diouf","sequence":"additional","affiliation":[{"name":"Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serkan","family":"Ozakbas","sequence":"additional","affiliation":[{"name":"Izmir University of Economics, Medical Point Hospital, Multiple Sclerosis Research Association, Konak\/Izmir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-0036","authenticated-orcid":false,"given":"Dana","family":"Horakova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Kubala","family":"Havrdova","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Patti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Eichau","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario Virgen Macarena, Institute of Biomedicine of Sevilla (IBIS), University of Seville, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raed","family":"Alroughani","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2902-5589","authenticated-orcid":false,"given":"Alessandra","family":"Lugaresi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche e Neuromotorie, Universit\u00e0 di Bologna, and IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Tomassini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Imaging and Clinical Sciences, University G. d\u2019Annunzio of Chieti-Pescara, Chieti, Italy; MS Centre, Clinical Neurology, SS. Annunziata University Hospital, Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Prat","sequence":"additional","affiliation":[{"name":"CHUM MS Center and Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Girard","sequence":"additional","affiliation":[{"name":"CHUM MS Center and Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Terzi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassem","family":"Yamout","sequence":"additional","affiliation":[{"name":"Harley Street Medical Center, Abu Dhabi, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia J","family":"Khoury","sequence":"additional","affiliation":[{"name":"Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Grammond","sequence":"additional","affiliation":[{"name":"CISSS Chaudi\u00e8re-Appalache, Levis, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Blanco","sequence":"additional","affiliation":[{"name":"Center of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6960-1265","authenticated-orcid":false,"given":"Vahid","family":"Shaygannejad","sequence":"additional","affiliation":[{"name":"Isfahan University of Medical Sciences, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Foschi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, MS Center\u2013Neurology Unit, S.Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3779-0934","authenticated-orcid":false,"given":"Andrea","family":"Surcinelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, MS Center\u2013Neurology Unit, S.Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Neri","sequence":"additional","affiliation":[{"name":"AUSL Romagna, Department of Diagnostic Imaging, S. 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Department of Neurology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-4498","authenticated-orcid":false,"given":"Nevin","family":"John","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences, Monash University, Clayton, VIC, Australia; Department of Neurology, Monash Health, Clayton, VIC, Australia; Department of Neurology, Monash Health, Clayton, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-4016","authenticated-orcid":false,"given":"Allan G","family":"Kermode","sequence":"additional","affiliation":[{"name":"Perron Institute for Neurological and Translational Science, Sir Charles Gairdner Hospital, QEIIMC, University of Western Australia, Nedlands, WA, Australia; Personalised Medicine Centre, Health Futures Institute, Murdoch University, Murdoch, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Fabis-Pedrini","sequence":"additional","affiliation":[{"name":"Perron Institute for Neurological and Translational Science, Sir Charles Gairdner Hospital, QEIIMC, University of Western Australia, Nedlands, WA, Australia; 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