{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T22:25:26Z","timestamp":1776378326569,"version":"3.51.2"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006978","name":"University of California Berkeley","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100006978","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative disorder for which there are currently no disease\u2010modifying treatments. Recent trials of potential therapies had durations of 12\u2009months, which may be insufficient because of nonrandom missingness due to death. Longer durations, incorporating PSP Rating Scale and survival, can reduce the potential for type II error. Selecting efficacy measures more sensitive to disease modification may facilitate identification of treatment effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to evaluate the simulated phase 3 PSP trial assessing the effect of disease\u2010modifying intervention on a novel combined primary endpoint comprising function (PSP Rating Scale) and survival, the Combined Assessment of Function and Survival (CAFS), and to determine operating characteristics of the CAFS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To simulate PSP progression in the trial population, we developed models of PSP Rating Scale and survival using data from published clinical studies. These models were used to define operating characteristics of the CAFS for use in a phase 3 trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The sample size determined (N\u2009=\u2009384; 1:1 randomization) would provide &gt;80% power to detect significant treatment effects on the CAFS compared with placebo. The CAFS provides good operating characteristics and increased power to detect moderate treatment effects on the PSP Rating Scale. We propose a trial design allowing potential detection of treatment effects at a preplanned interim analysis after participants complete 12\u2009months of treatment, with assessment of effects of treatment (\u226424\u2009months) on survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Use of the CAFS could provide a comprehensive and robust estimate of the clinical benefit of future therapies. \u00a9 2024 UCB. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30027","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T07:26:37Z","timestamp":1730186797000},"page":"97-107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Combined Assessment of Function and Survival to Demonstrate the Effect of Treatment on Progressive Supranuclear Palsy"],"prefix":"10.1002","volume":"40","author":[{"given":"Massimiliano","family":"Germani","sequence":"first","affiliation":[{"name":"UCB  Braine\u2010l'Alleud Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0635-2485","authenticated-orcid":false,"given":"Irene","family":"Rebollo Mesa","sequence":"additional","affiliation":[{"name":"UCB  Braine\u2010l'Alleud Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim J.","family":"Buchanan","sequence":"additional","affiliation":[{"name":"UCB  Braine\u2010l'Alleud Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"De Bruyn","sequence":"additional","affiliation":[{"name":"UCB  Braine\u2010l'Alleud Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Gasalla","sequence":"additional","affiliation":[{"name":"UCB  Morrisville North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans Lieve G.","family":"Van Tricht","sequence":"additional","affiliation":[{"name":"UCB  Braine\u2010l'Alleud Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Ewen","sequence":"additional","affiliation":[{"name":"UCB  Slough United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence I.","family":"Golbe","sequence":"additional","affiliation":[{"name":"Rutgers Robert Wood Johnson Medical School  New Brunswick New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Boxer","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  San Francisco USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnter","family":"H\u00f6glinger","sequence":"additional","affiliation":[{"name":"Department of Neurology LMU University Hospital, Ludwig\u2010Maximilians\u2010Universit\u00e4t (LMU)  Munich Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases (DNZE)  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"National Institute of Neurological Disorders and Stroke (NINDS).Progressive supranuclear palsy (PSP); Accessed August 08 2024https:\/\/www.ninds.nih.gov\/health-information\/disorders\/progressive-supranuclear-palsy-psp."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26987"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30157-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.09.041"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2013.06.014"},{"key":"e_1_2_8_7_1","volume-title":"Progressive supranuclear palsy in 2022: recent developments and an eye to the future","author":"Lyons S","year":"2022"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.09.020"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02158-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-016-0422-5"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00127B"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01455-x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30489-0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26580"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm032"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074486"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25824"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000266"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2016.04.021"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8169-1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26694"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12475"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2012.762930"},{"key":"e_1_2_8_24_1","unstructured":"Food and Drug Administration (FDA).Amyotrophic lateral sclerosis: developing drugs for treatment guidance for industry; Accessed August 08 2024https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry."},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70088-2"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn291"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12207"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.100982"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00637-0"},{"issue":"97","key":"e_1_2_8_30_1","first-page":"1","article-title":"Simulating survival data using the simsurv R package","volume":"3","author":"Brilleman SL","year":"2021","journal-title":"J Stat Softw"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-022-01271-2"},{"key":"e_1_2_8_32_1","article-title":"Efficiency of multivariate tests in trials in progressive supranuclear palsy","author":"Yousefi E","year":"2023","journal-title":"arXiv"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12678"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.30027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:05:07Z","timestamp":1760951107000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.30027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,29]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/mds.30027"],"URL":"https:\/\/doi.org\/10.1002\/mds.30027","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,29]]},"assertion":[{"value":"2024-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}