{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:54:19Z","timestamp":1791942859971,"version":"4.3.4"},"reference-count":14,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.ebiom.2025.105802","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T18:01:53Z","timestamp":1750269713000},"page":"105802","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Uncovering a bias in estimated treatment effects on PIRA in multiple sclerosis clinical trials"],"prefix":"10.1016","volume":"117","author":[{"given":"Noemi","family":"Montobbio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bovis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Signori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Carmisciano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Schiavetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ponzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Tur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Granziera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Cagol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas L.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6892-104X","authenticated-orcid":false,"given":"Maria Pia","family":"Sormani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.ebiom.2025.105802_bib1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/ana.25463","article-title":"Silent progression in disease activity-free relapsing multiple sclerosis","volume":"85","author":"University of California, San Francisco MS-EPIC Team","year":"2019","journal-title":"Ann Neurol"},{"issue":"9","key":"10.1016\/j.ebiom.2025.105802_bib2","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1001\/jamaneurol.2020.1568","article-title":"Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials","volume":"77","author":"Kappos","year":"2020","journal-title":"JAMA Neurol"},{"issue":"9","key":"10.1016\/j.ebiom.2025.105802_bib3","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire disability","volume":"145","author":"Lublin","year":"2022","journal-title":"Brain"},{"issue":"7","key":"10.1016\/j.ebiom.2025.105802_bib4","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1001\/jamaneurol.2022.1025","article-title":"Association of brain atrophy with disease progression independent of relapse activity in patients with relapsing multiple sclerosis","volume":"79","author":"Cagol","year":"2022","journal-title":"JAMA Neurol"},{"issue":"11","key":"10.1016\/j.ebiom.2025.105802_bib5","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1001\/jamaneurol.2023.3331","article-title":"Harmonizing definitions for progression independent of relapse activity in multiple sclerosis: a systematic review","volume":"80","author":"M\u00fcller","year":"2023","journal-title":"JAMA Neurol"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105802_bib6","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000209444","article-title":"Using the progression independent of relapse activity framework to unveil the pathobiological foundations of multiple sclerosis","volume":"103","author":"Ciccarelli","year":"2024","journal-title":"Neurology"},{"issue":"4\u20135","key":"10.1016\/j.ebiom.2025.105802_bib7","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1177\/13524585231157211","article-title":"The impact of relapse definition and measures of durability on MS clinical trial outcomes","volume":"29","author":"Satyanarayan","year":"2023","journal-title":"Mult Scler"},{"issue":"10","key":"10.1016\/j.ebiom.2025.105802_bib8","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1177\/1352458520971819","article-title":"Siponimod: disentangling disability and relapses in secondary progressive multiple sclerosis","volume":"27","author":"Cree","year":"2021","journal-title":"Mult Scler"},{"issue":"3","key":"10.1016\/j.ebiom.2025.105802_bib9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1056\/NEJMoa1601277","article-title":"Ocrelizumab versus Interferon beta-1a in relapsing multiple sclerosis","volume":"376","author":"Hauser","year":"2017","journal-title":"N Engl J Med"},{"issue":"7","key":"10.1016\/j.ebiom.2025.105802_bib10","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1177\/1352458517709619","article-title":"Greater sensitivity to multiple sclerosis disability worsening and progression events using a roving versus a fixed reference value in a prospective cohort study","volume":"24","author":"Kappos","year":"2018","journal-title":"Mult Scler"},{"issue":"1","key":"10.1016\/j.ebiom.2025.105802_bib11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/ana.27093","article-title":"Relapse-associated and relapse-independent contribution to overall expanded disability status scale progression in multiple sclerosis patients diagnosed in different eras","volume":"97","author":"Montobbio","year":"2024","journal-title":"Ann Neurol"},{"issue":"23","key":"10.1016\/j.ebiom.2025.105802_bib12","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1002\/sim.8333","article-title":"Bayesian inference for a principal stratum estimand to assess the treatment effect in a subgroup characterized by postrandomization event occurrence","volume":"38","author":"Magnusson","year":"2019","journal-title":"Stat Med"},{"issue":"10127","key":"10.1016\/j.ebiom.2025.105802_bib13","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0140-6736(18)30475-6","article-title":"Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study","volume":"391","author":"Kappos","year":"2018","journal-title":"Lancet"},{"issue":"9","key":"10.1016\/j.ebiom.2025.105802_bib14","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1177\/13524585241243157","article-title":"Creating an automated tool for a consistent and repeatable evaluation of disability progression in clinical studies for multiple sclerosis","volume":"30","author":"Montobbio","year":"2024","journal-title":"Mult Scler"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396425002464?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396425002464?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T16:16:15Z","timestamp":1762618575000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396425002464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":14,"alternative-id":["S2352396425002464"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2025.105802","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Uncovering a bias in estimated treatment effects on PIRA in multiple sclerosis clinical trials","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2025.105802","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"105802"}}