{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T13:44:31Z","timestamp":1782999871241,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biometrical J"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Medical advances have increased cancer survival rates and the possibility of finding a cure. Hence, it is crucial to evaluate the impact of treatments both in terms of cure and prolongation of survival. To achieve this, we may use a Cox proportional hazards cure model. However, a significant challenge in applying such a model is the potential presence of partially observed covariates. We aim to refine the methods for imputing partially observed covariates based on multiple imputation and fully conditional specification approaches. To be more specific, we consider a general case in which different covariate vectors are used to model the probability of cure and the survival of patients who are not cured. In a large\u2010scale simulation experiment, we investigated the performance of the multiple imputation procedure based either on the exact conditional distribution or on an approximate imputation model, which helps to draw imputed values at a lower computational cost. To assess the effectiveness of these approaches, we compare them with a complete\u2010case analysis and an analysis that includes all available covariates in modeling both cure probabilities and the survival of the uncured. We discuss the application of these techniques to a real\u2010world dataset from the BO06 clinical trial on\u00a0osteosarcoma.<\/jats:p>","DOI":"10.1002\/bimj.70144","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T07:06:03Z","timestamp":1780902363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Multiple Imputation Approach to Distinguish Curative From Life\u2010Prolonging Effects in the Presence of Missing Covariates"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6159-8059","authenticated-orcid":false,"given":"Marta","family":"Cipriani","sequence":"first","affiliation":[{"name":"Department of Statistical Sciences Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5588-0277","authenticated-orcid":false,"given":"Marta","family":"Fiocco","sequence":"additional","affiliation":[{"name":"Leiden University, Mathematical Institute Leiden The Netherlands"},{"name":"Department of Biomedical Data Science Leiden University Medical Centre Leiden The Netherlands"},{"name":"Princess Maxima Centre for Pediatric Oncology, Trial and Data Center Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Alf\u00f2","sequence":"additional","affiliation":[{"name":"Department of Statistical Sciences Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Quelhas","sequence":"additional","affiliation":[{"name":"Leiden University, Mathematical Institute Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-4307","authenticated-orcid":false,"given":"Eni","family":"Musta","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Korteweg\u2010de Vries Institute for Mathematics Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-statistics-031017-100101"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv114"},{"key":"e_1_2_11_4_1","unstructured":"Bartlett J. T.Morris K.White andI.White.2023.smcfcs: Substantive Model Compatible Fully Conditional Specification. R Package Version 1.5.5."},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280214521348"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7048"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.2307\/2529620"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2012.08.013"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1972.tb00899.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1987.5.1.21"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/64.1.43"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mph.0000212944.82361.1d"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmva.2014.06.002"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/57.1.97"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10985-017-9415-2"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz032"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/79.3.531"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-019-03797-3"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.01.008"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781315112084-22"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djk015"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198606193142502"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119013563"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5378"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjs.11771"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216677748"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1177010269"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.1699114"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8086"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-052941"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.4236\/am.2016.710093"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2000.00237.x"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1201\/9780429032301"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470316696"},{"key":"e_1_2_11_35_1","volume-title":"Multiple Imputation for Nonresponse in Surveys","author":"Rubin D. B.","year":"2004"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/00949655.2018.1491577"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2000.00227.x"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1201\/9780429492259"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/10629360600810434"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v045.i03"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4067"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3618"},{"key":"e_1_2_11_43_1","doi-asserted-by":"crossref","unstructured":"Xie P. M.Escobar\u2010Bach andI.vanKeilegom.2023. \u201cTesting for Sufficient Follow\u2010Up in Censored Survival Data by Using Extremes.\u201darXiv Preprint arXiv:2309.00868.","DOI":"10.1002\/bimj.202400033"},{"key":"e_1_2_11_44_1","unstructured":"Yuen T. andE.Musta.2024. \u201cTesting for Sufficient Follow\u2010Up in Survival Data With a Cure Fraction.\u201darXiv Preprint arXiv:2403.16832."},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/wics.1402"}],"container-title":["Biometrical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bimj.70144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bimj.70144","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bimj.70144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:59:38Z","timestamp":1782997178000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bimj.70144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/bimj.70144"],"URL":"https:\/\/doi.org\/10.1002\/bimj.70144","archive":["Portico"],"relation":{},"ISSN":["0323-3847","1521-4036"],"issn-type":[{"value":"0323-3847","type":"print"},{"value":"1521-4036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-06-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70144"}}