{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:07:02Z","timestamp":1791990422750,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AG042791"],"award-info":[{"award-number":["U01AG042791"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AG042791\u2010S1"],"award-info":[{"award-number":["U01AG042791\u2010S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Estimating treatment effects as time savings in disease progression may be more easily interpretable than assessing the absolute difference or a percentage reduction. In this study, we investigate the statistical considerations of the existing method for estimating time savings and propose alternative complementary methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We propose five alternative methods to estimate the time savings from different perspectives. These methods are applied to simulated clinical trial data that mimic or modify the Clinical Dementia Rating Sum of Boxes progression trajectories observed in the Clarity AD lecanemab trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Our study demonstrates that the proposed methods can generate more precise estimates by considering two crucial factors: (1) the absolute difference between treatment arms, and (2) the observed progression rate in the treatment arm.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Quantifying treatment effects as time savings in disease progression offers distinct advantages. To provide comprehensive estimations, it is important to use various methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We explore the statistical considerations of the current method for estimating time savings.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We proposed alternative methods that provide time savings estimations based on the observed absolute differences.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>By using various methods, a more comprehensive estimation of time savings can be achieved.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14035","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T09:19:52Z","timestamp":1718961592000},"page":"5421-5433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Statistical considerations when estimating time\u2010saving treatment effects in Alzheimer's disease clinical trials"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-8737","authenticated-orcid":false,"given":"Guoqiao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Division of Biostatistics, School of Medicine Washington University  St. Louis Missouri USA"},{"name":"Division of Biostatistics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Cutter","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil P.","family":"Oxtoby","sequence":"additional","affiliation":[{"name":"Department of Computer Science University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guogen","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whedy","family":"Wang","sequence":"additional","affiliation":[{"name":"Tenaya Therapeutics  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Mangal","sequence":"additional","affiliation":[{"name":"Solara Consulting Corp.  North Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Liao","sequence":"additional","affiliation":[{"name":"Neogene Therapeutics Inc.  Santa Monica California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge J.","family":"Llibre\u2010Guerra","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Biostatistics, School of Medicine Washington University  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Biostatistics, School of Medicine Washington University  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjie","family":"Xiong","sequence":"additional","affiliation":[{"name":"Division of Biostatistics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"McDade","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Biostatistics, School of Medicine Washington University  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Delmar","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Biostatistics, School of Medicine Washington University  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lon","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and The Behavioral Sciences Department of Neurology Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01369-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7811"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12959"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.063092"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.9581"},{"issue":"3","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.14283\/jpad.2023.50","article-title":"Time saved'as a demonstration of clinical meaningfulness and illustrated using the donanemab TRAILBLAZER\u2010ALZ study findings","volume":"10","author":"Dickson S","year":"2023","journal-title":"J Prev Alzheimers Dis"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12286"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-01124-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01369-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2305032"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228064"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2307\/2532090"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.30"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100708"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2015.06.006"},{"key":"e_1_2_8_19_1","unstructured":"WangG.An Evaluation of Sample Size Re\u2010Estimation Adaptive Designs and Delayed\u2010Start Designs for Alzheimer's Disease Trials.The University of Alabama at Birmingham;2014."}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:19:30Z","timestamp":1759943970000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,21]]},"references-count":18,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/alz.14035"],"URL":"https:\/\/doi.org\/10.1002\/alz.14035","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,21]]},"assertion":[{"value":"2024-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}