{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:02:54Z","timestamp":1790337774135,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["72174207"],"award-info":[{"award-number":["72174207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Prior studies suggest that proportional\u2010hazards violations (PHVs) occur in oncology randomized controlled trials (RCTs) and may affect conclusions, but evidence has largely focused on initial reports rather than updated analyses. We examined PH testing practices, frequency, patterns, and statistical implications of PHVs in updated oncology RCTs. We focused on oncology RCTs supporting US Food and Drug Administration approvals. Phase II\u2010III oncology RCTs supporting FDA approvals between 2006 and 2025 were identified. Individual patient data were reconstructed from Kaplan\u2013Meier curves. PHVs were assessed using Schoenfeld residuals. Treatment effects were analyzed with Cox proportional\u2010hazards models, log\u2010rank tests, MaxCombo, and restricted mean survival time difference (RMSD). Two hundred seventy endpoint comparisons (150 overall survival [OS], 120 non\u2010OS) from 168 RCTs were included. PH testing dropped from 24.1% in initial reports to 11.5% in updates (McNemar\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Although PH testing increased over the past decade in initial publications (Wald\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), no trend in updates (Wald\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.29). PHV frequency was numerically higher in updated than initial analyses (38.9% vs. 33.0%). Non\u2010OS endpoints, metastatic settings, and immunotherapy or targeted\u2010therapy regimens were associated with PHVs. Among updated analyses, nominal significance differences between PH\u2010dependent and alternative methods were more frequent with PHVs (MaxCombo: 11.4% vs. 3.6%, chi\u2010square\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.012; RMSD: 8.6% vs. 2.4%, chi\u2010square\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.021). PHV patterns were diminishing effects (35.2%), delayed separation (27.6%), and crossing hazards (27.6%). PH testing declined in updated analyses despite numerically more frequent PHVs. Although updates are descriptive and do not invalidate original conclusions, unrecognized non\u2010proportionality may affect long\u2010term benefit interpretation, supporting PH diagnostics and prespecified complementary analyses.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70748","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:26:16Z","timestamp":1790335576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Limited Assessment of Proportional Hazards Despite More Frequent Violations Identified in Updated Oncology Trial Analyses: Frequency, Patterns, and Statistical Implications"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7709-9374","authenticated-orcid":false,"given":"Mingye","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pharmacoeconomics, School of International Pharmaceutical Business China Pharmaceutical University  Nanjing Jiangsu China"},{"name":"Center for Pharmacoeconomics and Outcomes Research China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taihang","family":"Shao","sequence":"additional","affiliation":[{"name":"JC School of Public Health and Primary Care, Faculty of Medicine The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqiao","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Pharmacoeconomics, School of International Pharmaceutical Business China Pharmaceutical University  Nanjing Jiangsu China"},{"name":"Center for Pharmacoeconomics and Outcomes Research China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacoeconomics, School of International Pharmaceutical Business China Pharmaceutical University  Nanjing Jiangsu China"},{"name":"Center for Pharmacoeconomics and Outcomes Research China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacoeconomics, School of International Pharmaceutical Business China Pharmaceutical University  Nanjing Jiangsu China"},{"name":"Center for Pharmacoeconomics and Outcomes Research China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pharmacoeconomics, School of International Pharmaceutical Business China Pharmaceutical University  Nanjing Jiangsu China"},{"name":"Center for Pharmacoeconomics and Outcomes Research China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacoeconomics, School of International Pharmaceutical Business China Pharmaceutical University  Nanjing Jiangsu China"},{"name":"Center for Pharmacoeconomics and Outcomes Research China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.282034"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201024\u20100566"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181c1ea43"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.2208"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2021.103350"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201021\u20100809"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1913662"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01308"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)01245\u2010X"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00193"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01792"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.51.2046"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2025.105123"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200214"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004710"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.188888"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2023.01.006"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201018\u20103999"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010147\u20108\u2010200710160\u201000010"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1405337"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010023\u201000723\u20104"},{"key":"e_1_2_12_23_1","unstructured":"\u201cGuideline 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