{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:00:47Z","timestamp":1792868447857,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer J."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Over the past 13 years, there have been advances in characterizing the patient experience in oncology trials, primarily using patient-reported outcomes (PROs). This review aims to provide details on the PRO measures and analyses used in multiple myeloma (MM) registrational trials. We identified registrational trials supporting MM indications from 2007 to 2020 from FDA databases. Trial protocols, statistical analysis plans, and clinical study reports were reviewed for PRO measures used, collection methods, statistical analyses, baseline and instrument completion definitions, and thresholds for clinical meaningfulness. Twenty-five trials supporting 20 MM indications were identified; 17 (68%) contained submitted PRO data. Of the 17 trials, 14 were randomized controlled trials and the remainder were single-arm trials. All but one trial were open label trials. Seven trials collected data electronically and five in paper format. The majority of trials evaluated at least two PRO measures (82%) with two trials (12%) utilizing four measures. Nine unique PRO measures were used, most commonly the EORTC QLQ-30 (87%), EQ-5D (65%), and QLQ-MY20 (47%). All 17 (100%) trials provided descriptive summaries, 10 (59%) carried out longitudinal mixed model analysis, 9 (53%) conducted responder analysis, and 2 (12%) did a basic inferential test. We noted substantial heterogeneity in terms of PRO collection methods, measures, definitions, and analyses, which may hinder the ability to effectively capture and interpret patient experience in future MM clinical trials. Further research is needed to determine the most appropriate approaches for statistical and analytical methodologies for PRO data in MM trials.<\/jats:p>","DOI":"10.1038\/s41408-021-00543-y","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T20:03:41Z","timestamp":1630440221000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Review of patient-reported outcomes in multiple myeloma registrational trials: highlighting areas for improvement"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-3885","authenticated-orcid":false,"given":"Laura L.","family":"Fernandes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindu","family":"Kanapuru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Horodniceanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gwise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Kluetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Bhatnagar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"543_CR1","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1016\/j.jval.2017.09.009","volume":"21","author":"PG Kluetz","year":"2018","unstructured":"Kluetz PG, Kanapuru B, Lemery S, Johnson LL, Fiero MH, Arscott K, et al. Informing the tolerability of cancer treatments using patient-reported outcome measures: summary of an FDA and Critical Path Institute workshop. Value Health. 2018;21:742\u201347.","journal-title":"Value Health"},{"key":"543_CR2","unstructured":"US Food and Drug Administration. Project patient voice. 2020. https:\/\/www.fda.gov\/about-fda\/oncology-center-excellence\/project-patient-voice. Accessed 26 May 2021."},{"key":"543_CR3","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/S1470-2045(19)30335-3","volume":"20","author":"MH Fiero","year":"2019","unstructured":"Fiero MH, Roydhouse JK, Vallejo J, King-Kallimanis BL, Kluetz PG, Sridhara R, et al. US Food and Drug Administration review of statistical analysis of patient-reported outcomes in lung cancer clinical trials approved between January, 2008, and December, 2017. Lancet Oncol. 2019;20:582\u201389.","journal-title":"Lancet Oncol"},{"issue":"Supplement_1","key":"543_CR4","doi-asserted-by":"publisher","first-page":"3450","DOI":"10.1182\/blood-2019-125798","volume":"134","author":"J Kim","year":"2019","unstructured":"Kim J, Kanapuru B, Roydhouse JK, Farrell AT, Bouchkouj N, Ezzeldin H, et al. 2017-2018 Hematology Drug Approvals at the Food and Drug Administration (FDA): communication of patient-reported outcomes (PRO) information in FDA clinical reviews and prescribing information (PI). Blood. 2019;134(Supplement_1):3450.","journal-title":"Blood"},{"key":"543_CR5","unstructured":"US Food and Drug Administration. CDER patient-focused drug development. 2021. https:\/\/www.fda.gov\/drugs\/developmentapprovalprocess\/ucm579400.htm. Accessed Apr 2021."},{"key":"543_CR6","unstructured":"114th US Congress. 21st Century Cures Act. 2016. https:\/\/www.congress.gov\/114\/plaws\/publ255\/PLAW-114publ255.pdf. Accessed 1 Apr 2021."},{"key":"543_CR7","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1093\/jnci\/djy130","volume":"111","author":"J Zhou","year":"2019","unstructured":"Zhou J, Vallejo J, Kluetz P, Pazdur R, Kim T, Keegan P, et al. Overview of oncology and hematology drug approvals at US Food and Drug administration between 2008 and 2016. J Natl Cancer Inst. 2019;111:449\u201358.","journal-title":"J Natl Cancer Inst"},{"key":"543_CR8","unstructured":"US Food and Drug Administration. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims. 2020. https:\/\/www.fda.gov\/media\/77832\/download. Accessed 1 Apr 2021."},{"key":"543_CR9","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1001\/jama.2017.21903","volume":"319","author":"M Calvert","year":"2018","unstructured":"Calvert M, Kyte D, Mercieca-Bebber R, Slade A, Chan AW, King MT, et al. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols: the SPIRIT-PRO extension. JAMA. 2018;319:483\u201394.","journal-title":"JAMA"},{"key":"543_CR10","unstructured":"US Food and Drug Administration. Core patient-reported outcomes in cancer clinical trials guidance for industry. 2020. https:\/\/www.fda.gov\/media\/149994\/download. Accessed Jul 2021."},{"key":"543_CR11","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.ejca.2004.10.017","volume":"41","author":"D Osoba","year":"2005","unstructured":"Osoba D, Bezjak A, Brundage M, Zee B, Tu D, Pater J, et al. Analysis and interpretation of health-related quality-of-life data from clinical trials: basic approach of the National Cancer Institute of Canada Clinical Trials Group. 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Clin Cancer Res. 2016;22:1553\u201358.","journal-title":"Clin Cancer Res"}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41408-021-00543-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-021-00543-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-021-00543-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T18:22:50Z","timestamp":1669918970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41408-021-00543-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["543"],"URL":"https:\/\/doi.org\/10.1038\/s41408-021-00543-y","relation":{},"ISSN":["2044-5385"],"issn-type":[{"value":"2044-5385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]},"assertion":[{"value":"7 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors are employed at the U.S. FDA and have no conflicts of interest to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"148"}}