{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T16:21:44Z","timestamp":1768407704927,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"18-19","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009812","name":"Princess Margaret Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009812","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["CXTD14\u201005"],"award-info":[{"award-number":["CXTD14\u201005"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12171329"],"award-info":[{"award-number":["12171329"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12371264"],"award-info":[{"award-number":["12371264"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Overall survival has been used as the primary endpoint for many randomized trials that aim to examine whether a new treatment is non\u2010inferior to the standard treatment or placebo control. When a new treatment is indeed non\u2010inferior in terms of survival, it may be important to assess other outcomes including health utility. However, analyzing health utility scores in a secondary analysis may have limited power since the primary objectives of the original study design may not include health utility. To comprehensively consider both survival and health utility, we developed a composite endpoint, HUS (Health Utility\u2010adjusted Survival), which combines both survival and utility. HUS has been shown to be able to increase statistical power and potentially reduce the required sample size compared to the standard overall survival endpoint. Nevertheless, the asymptotic properties of the test statistics of the HUS endpoint have yet to be fully established. Besides that, the standard version of HUS cannot be applied to or has limited performance in certain scenarios, where extensions are needed. In this manuscript, we propose various methodological extensions of HUS and derive the asymptotic distributions of the test statistics. By comprehensive simulation studies and a data application using retrospective data based on a translational patient cohort in Princess Margaret Cancer Centre, we demonstrate the better efficiency and feasibility of HUS compared to different methods.<\/jats:p>","DOI":"10.1002\/sim.70215","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T12:51:17Z","timestamp":1754571077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Health Utility Survival for Randomized Clinical Trials: Extensions and Statistical Properties"],"prefix":"10.1002","volume":"44","author":[{"given":"Yangqing","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Biostatistics University Health Network  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0440-530X","authenticated-orcid":false,"given":"Meiling","family":"Hao","sequence":"additional","affiliation":[{"name":"School of Statistics University of International Business and Economics  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao Hui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology University Health Network  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Liu","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Medical Oncology and Hematology Princess Margaret Cancer Centre  Toronto Ontario Canada"},{"name":"Dalla Lana School of Public Health University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R.","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014H&amp;N Surgery University Health Network  Toronto Ontario Canada"},{"name":"Institute of Health Policy, Management and Evaluation University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University Health Network  Toronto Ontario Canada"},{"name":"Dalla Lana School of Public Health University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta21170"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.10.1888"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477\u20107525\u20101\u201054"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2010.11.017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780091106"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010114\u20108\u2010621"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.15.1039"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006\u2010341X.2000.00173.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.20949"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/11535290\u2010000000000\u201000000"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102021\u2010147112"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clbc.2021.12.008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097\u20100258(19980615)17:11<1215::aid\u2010sim844>3.0.co;2\u2010y"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477\u20107525\u20101\u201080"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldq033"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphs.12218"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vhri.2019.07.005"},{"issue":"10","key":"e_1_2_9_19_1","first-page":"1","article-title":"Methods for the Analysis of Quality\u2010of\u2010Life and Survival Data in Health Technology Assessment","volume":"3","author":"Billingham L. 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