{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:55:05Z","timestamp":1790826905410,"version":"4.1.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Qual Life Res"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>The clinical relevance of different time-to-deterioration <jats:bold>(<\/jats:bold>TTD) definitions for patient-reported outcomes were explored.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>TTD definitions differing by reference score and deterioration event were used to analyse data from the phase 3 FLAURA trial of first-line osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small cell lung cancer. Pre-specified key symptoms were fatigue, appetite loss, cough, chest pain and dyspnoea, scored using the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13 questionnaires (\u2265\u200910-point difference\u2009=\u2009clinically relevant).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>No significant treatment differences in TTD (distributions) were observed using definitions based on transient or definitive deterioration alone. TTD definitions based on definitive, sustained deterioration, with death not included as an event, yielded a significant treatment difference for dyspnoea (hazard ratio [HR] 0.71; <jats:italic>P<\/jats:italic>\u2009=\u20090.034) when baseline was the reference, and for cough (HR 0.70; <jats:italic>P<\/jats:italic>\u2009=\u20090.009) and dyspnoea (HR 0.71; <jats:italic>P<\/jats:italic>\u2009=\u20090.004) when best previous score was the reference. With death included as an event, treatment differences were significant for dyspnoea (HR 0.70; <jats:italic>P<\/jats:italic>\u2009=\u20090.025) when baseline was the reference, and for cough (HR 0.70; <jats:italic>P<\/jats:italic>\u2009=\u20090.011), dyspnoea (HR 0.71; <jats:italic>P<\/jats:italic>\u2009=\u20090.003) and chest pain (HR 0.71; <jats:italic>P<\/jats:italic>\u2009=\u20090.038) when best previous score was the reference. Irrespective of definition, TTD for appetite loss and fatigue did not differ significantly between arms.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This exploratory work showed that different TTD definitions yield different magnitudes of treatment difference, highlighting the importance of pre-specifying TTD definitions upfront in clinical trials.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Clinical trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov NCT02296125.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11136-022-03088-0","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T09:03:04Z","timestamp":1643619784000},"page":"2535-2543","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Time to deterioration of patient-reported outcomes in non-small cell lung cancer: exploring different definitions"],"prefix":"10.1007","volume":"31","clinical-trial-number":[{"clinical-trial-number":"nct02296125","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Andrew","family":"Walding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Skaltsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Casamayor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ryd\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"issue":"1","key":"3088_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s11136-013-0583-6","volume":"24","author":"A Anota","year":"2015","unstructured":"Anota, A., Hamidou, Z., Paget-Bailly, S., Chibaudel, B., Bascoul-Mollevi, C., Auquier, P., Westeel, V., Fiteni, F., Borg, C., & Bonnetain, F. 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KS and MC are employed by IQVIA, which received funds from AstraZeneca to conduct the time-to-deterioration analysis of the study data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The FLAURA study was approved by the institutional review board and\/or independent ethics committee associated with each study centre.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients in the FLAURA study provided written informed consent before any study-specific procedures were performed.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}