{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:10:20Z","timestamp":1791537020856,"version":"4.3.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T00:00:00Z","timestamp":1685318400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T00:00:00Z","timestamp":1685318400000},"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":["BMC Med Res Methodol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In economic evaluations, survival is often extrapolated to smooth out the Kaplan-Meier estimate and because the available data (e.g., from randomized controlled trials) are often right censored. Validation of the accuracy of extrapolated results can depend on the length of follow-up and the assumptions made about the survival hazard. Here, we analyze the accuracy of different extrapolation techniques while varying the data cut-off to estimate long-term survival in newly diagnosed multiple myeloma (MM) patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Empirical data were available from a randomized controlled trial and a registry for MM patients treated with melphalan\u2009+\u2009prednisone, thalidomide, and bortezomib- based regimens. Standard parametric and spline models were fitted while artificially reducing follow-up by introducing database locks. The maximum follow-up for these locks varied from 3 to 13 years. Extrapolated (conditional) restricted mean survival time (RMST) was compared to the Kaplan-Meier RMST and models were selected according to statistical tests, and visual fit.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>For all treatments, the RMST error decreased when follow-up and the absolute number of events increased, and censoring decreased. The decline in RMST error was highest when maximum follow-up exceeded six years. However, even when censoring is low there can still be considerable deviations in the extrapolated RMST conditional on survival until extrapolation when compared to the KM-estimate.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We demonstrate that both standard parametric and spline models could be worthy candidates when extrapolating survival for the populations examined. Nevertheless, researchers and decision makers should be wary of uncertainty in results even when censoring has decreased, and the number of events has increased.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12874-023-01952-2","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T10:03:21Z","timestamp":1685354601000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Extrapolating empirical long-term survival data: the impact of updated follow-up data and parametric extrapolation methods on survival estimates in multiple myeloma"],"prefix":"10.1186","volume":"23","author":[{"given":"LJ","family":"Bakker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FW","family":"Thielen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WK","family":"Redekop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CA Uyl-de","family":"Groot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HM","family":"Blommestein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,29]]},"reference":[{"key":"1952_CR1","doi-asserted-by":"crossref","unstructured":"Sharma D, Aggarwal AK, Downey LE, Prinja S. National healthcare economic evaluation guidelines: a cross-country comparison. PharmacoEconomics-Open. 2021 Sep;5(3):349\u201364.","DOI":"10.1007\/s41669-020-00250-7"},{"key":"1952_CR2","unstructured":"Dutch Pharmacoeconomic Guidelines [Internet] Diemen: National Health Care Institute the Netherlands. Available from: https:\/\/www.zorginstituutnederland.nl\/publicaties\/publicatie\/2016\/02\/29\/richtlijn-voor-het-uitvoeren-van-economische-evaluaties-in-de-gezondheidszorg."},{"key":"1952_CR3","doi-asserted-by":"crossref","unstructured":"Latimer NR. Survival analysis for economic evaluations alongside clinical trials\u2014extrapolation with patient-level data: inconsistencies, limitations, and a practical guide. Med Decis Making. 2013 Aug;33(6):743\u201354.","DOI":"10.1177\/0272989X12472398"},{"key":"1952_CR4","doi-asserted-by":"crossref","unstructured":"Everest L, Blommaert S, Chu RW, Chan KK, Parmar A. Parametric Survival Extrapolation of early Survival data in economic analyses: a comparison of projected Versus observed updated survival. Value in Health. 2021 Nov 24.","DOI":"10.1016\/j.jval.2021.10.004"},{"key":"1952_CR5","doi-asserted-by":"crossref","unstructured":"Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Pour L. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. The Lancet. 2020 Jan 11;395(10218):132 \u2013 41.6.","DOI":"10.1016\/S0140-6736(19)32956-3"},{"key":"1952_CR6","doi-asserted-by":"crossref","unstructured":"Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Hockaday A, Jones JR, Kishore B, Garg M, Williams CD. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. The Lancet Oncology. 2019 Jan 1;20(1):57\u201373.","DOI":"10.1016\/S1470-2045(18)30687-9"},{"key":"1952_CR7","doi-asserted-by":"crossref","unstructured":"Jackson C, Stevens J, Ren S, Latimer N, Bojke L, Manca A, Sharples L. Extrapolating survival from randomized trials using external data: a review of methods. Med Decis Making. 2017 May;37(4):377\u201390.","DOI":"10.1177\/0272989X16639900"},{"key":"1952_CR8","unstructured":"Rutherford MJ, Lambert PC, Sweeting MJ, Pennington R, Crowther MJ, Abrams KR, Latimer NR. NICE DSU Technical Support Document 21. Flexible Methods for Survival Analysis. Department of Health Sciences, University of Leicester, Leicester, UK. 2020 Jan 23:1\u201397."},{"key":"1952_CR9","doi-asserted-by":"crossref","unstructured":"Gray J, Sullivan T, Latimer NR, Salter A, Sorich MJ, Ward RL, Karnon J. Extrapolation of survival curves using standard parametric models and flexible parametric spline models: comparisons in large registry cohorts with advanced cancer. Med Decis Making. 2021 Feb;41(2):179\u201393.","DOI":"10.1177\/0272989X20978958"},{"key":"1952_CR10","unstructured":"Latimer N. NICE DSU technical support document 14: survival analysis for economic evaluations alongside clinical trials-extrapolation with patient-level data. Rep Decis Support Unit. 2011 Jun."},{"key":"1952_CR11","doi-asserted-by":"crossref","unstructured":"Vickers A. An evaluation of survival curve extrapolation techniques using long-term observational cancer data. Med Decis Making. 2019 Nov;39(8):926\u201338.","DOI":"10.1177\/0272989X19875950"},{"key":"1952_CR12","doi-asserted-by":"crossref","unstructured":"Bullement A, Willis A, Amin A, Schlichting M, Hatswell AJ, Bharmal M. Evaluation of survival extrapolation in immuno-oncology using multiple pre-planned data cuts: learnings to aid in model selection. BMC Med Res Methodol. 2020 Dec;20(1):1\u20134.","DOI":"10.1186\/s12874-020-00997-x"},{"key":"1952_CR13","doi-asserted-by":"crossref","unstructured":"Davies C, Briggs A, Lorgelly P, Garellick G, Malchau H. The \u201chazards\u201d of extrapolating survival curves. Med Decis Making. 2013 Apr;33(3):369\u201380.","DOI":"10.1177\/0272989X12475091"},{"key":"1952_CR14","doi-asserted-by":"crossref","unstructured":"Kearns B, Stevenson MD, Triantafyllopoulos K, Manca A. Comparing current and emerging practice models for the extrapolation of survival data: a simulation study and case-study. BMC Med Res Methodol. 2021 Dec;21(1):1\u20131.","DOI":"10.1186\/s12874-021-01460-1"},{"key":"1952_CR15","doi-asserted-by":"crossref","unstructured":"Bullement A, Latimer NR, Gorrod HB. Survival extrapolation in cancer immunotherapy: a validation-based case study. Value in Health. 2019 Mar 1;22(3):276 \u2013 83.","DOI":"10.1016\/j.jval.2018.10.007"},{"key":"1952_CR16","doi-asserted-by":"crossref","unstructured":"Ouwens MJ, Mukhopadhyay P, Zhang Y, Huang M, Latimer N, Briggs A. Estimating lifetime benefits associated with immuno-oncology therapies: challenges and approaches for overall survival extrapolations. PharmacoEconomics. 2019 Sep;37(9):1129\u201338.","DOI":"10.1007\/s40273-019-00806-4"},{"key":"1952_CR17","doi-asserted-by":"crossref","unstructured":"Gibson E, Koblbauer I, Begum N, Dranitsaris G, Liew D, McEwan P, Monfared AA, Yuan Y, Juarez-Garcia A, Tyas D, Lees M. Modelling the survival outcomes of immuno-oncology drugs in economic evaluations: a systematic approach to data analysis and extrapolation. PharmacoEconomics. 2017 Dec;35(12):1257\u201370.","DOI":"10.1007\/s40273-017-0558-5"},{"key":"1952_CR18","doi-asserted-by":"crossref","unstructured":"Lanitis T, Proskorovsky I, Ambavane A, Hunger M, Zheng Y, Bharmal M, Phatak H. Survival analysis in patients with metastatic merkel cell carcinoma treated with Avelumab. Advances in therapy. 2019 Sep;36(9):2327\u201341.","DOI":"10.1007\/s12325-019-01034-0"},{"key":"1952_CR19","doi-asserted-by":"crossref","unstructured":"Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, Zweegman S, van Marwijk Kooy M, Van Der Griend R, Lokhorst H, Sonneveld P. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. Journal of Clinical Oncology. 2010 Jul 1;28(19):3160-6.","DOI":"10.1200\/JCO.2009.26.1610"},{"key":"1952_CR20","doi-asserted-by":"crossref","unstructured":"Blommestein HM, Franken MG, Uyl-de Groot CA. A practical guide for using registry data to inform decisions about the cost effectiveness of new cancer drugs: lessons learned from the PHAROS registry. PharmacoEconomics. 2015 Jun;33(6):551\u201360.","DOI":"10.1007\/s40273-015-0260-4"},{"key":"1952_CR21","doi-asserted-by":"publisher","unstructured":"Verelst SGR, Blommestein HM, De Groot S, Gonzalez-McQuire S, DeCosta L, de Raad JB, Uyl-de Groot CA, Sonneveld P. Long-term outcomes in patients with multiple myeloma: a retrospective analysis of the Dutch Population-based HAematological Registry for Observational Studies (PHAROS). Hemasphere 2018 May 4;2(4):e45. doi: https:\/\/doi.org\/10.1097\/HS9.0000000000000045. PMID: 31723779; PMCID: PMC6746001.","DOI":"10.1097\/HS9.0000000000000045"},{"key":"1952_CR22","unstructured":"Blommestein H, Uyl-de Groot C, Visser O, Oerlemans S, Verelst S, van den Broek E, Issa D, Aarts M, Louwman M, Sonneveld P, Postuma W, Coebergh JW, van de Poll L, Huijgens P. 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Blood, The Journal of the American Society of Hematology. 2016 Mar 3;127(9):1109-16.","DOI":"10.1182\/blood-2015-11-679415"}],"container-title":["BMC Medical Research Methodology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12874-023-01952-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12874-023-01952-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12874-023-01952-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T10:04:04Z","timestamp":1685354644000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedresmethodol.biomedcentral.com\/articles\/10.1186\/s12874-023-01952-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,29]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1952"],"URL":"https:\/\/doi.org\/10.1186\/s12874-023-01952-2","relation":{},"ISSN":["1471-2288"],"issn-type":[{"value":"1471-2288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,29]]},"assertion":[{"value":"9 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Neither obtaining informed consent from patients nor approval by a medical ethics committee is obligatory for this type of observational studies containing no directly identifiable data (art. 9.2 sub j General Data Protection Regulation, art. 24 Dutch GDPR Implementation Act jo). Administrative permission for use of the anonymized data from the Netherlands Cancer Registry (NCR) was granted through the supervisory committee of the NCR. Administrative permission for use of the anonymized data from the Dutch Haemato-oncology Foundation for Adults in the Netherlands (HOVON) was granted by the HOVON executive board and the HOVON multiple myeloma working group. All data provided to the researchers by the NCR & HOVON was in anonymized format. This study was conducted according to the principles of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"FT reports previous consultation for AstraZeneca, Optimax Access, Dark Peak Analytics, and grants from Celgene outside the submitted work. Previous and ongoing research was or is partly funded by the CADTH (Canadian Agency for Drugs and Technologies in Health), the Dutch Ministry of Health, Welfare and Sport, and the European Haematology Association. HB reports previous research grants from BMS (Celgene BV), advisory board fee from Pfizer, outside the submitted work paid to the institute; Previous and ongoing research was or is partly funded by the CADTH (Canadian Agency for Drugs and Technologies in Health), the Dutch Healthcare Institute, and Medical Delta. LB reports previous and ongoing research grants from the European H2020 Research Programme and the Convergence Program outside the submitted work. WR reports previous and ongoing research grants from the European H2020 Research Programme and the Convergence Program outside the submitted work. CUG reports unrestricted grants from Boehringer Ingelheim, Astellas, Sanofi, Janssen-Cilag, Bayer, Sanofi, Amgen, Merck, Gilead, Novartis, and Astra Zeneca, Roche, and grants from European Research Programmes, CADTH (Canadian Agency for Drugs and Technologies in Health), the Dutch Healthcare Institute, the European Haematology Association, and Dutch Ministry of Health. All grants were outside the submitted work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"132"}}