{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:35:01Z","timestamp":1775583301341,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Fondazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["18150"],"award-info":[{"award-number":["18150"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>One cause of poor outcomes in children of low-income countries affected by acute lymphoblastic leukaemia (ALL) is loss to follow-up due to abandonment of treatment. Assuming this type of loss to follow-up as independent censoring, as in standard Kaplan\u2013Meier estimates, ignores the likely association of abandonment with biologic and socio-economic factors related to outcome. Moreover, when comparing treatment protocols adopted in different time periods, possible imbalances in patients\u2019 characteristics must be considered. We aim to compare the outcome of children enrolled in two subsequent protocols for ALL treatment (2000\u20132007 and 2008\u20132015) in Honduras, taking both dependent censoring due to abandonment of treatment and imbalances between patient characteristics into account.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Marginal structural models based on inverse probability of treatment and censoring (IPTC) weighting allow the estimation of potential event-free survival (EFS) as if no abandonment of treatment occurred and the whole cohort was exposed, or not, to both protocols. An Aalen additive model and a logistic-regression model were used to build abandonment and treatment weights, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The two protocols recruited 514 and 717 patients. Measured baseline covariates in both protocols were gender, age, white blood cell count, central nervous system involvement, tumour histology and socio-economic status. The potential EFS is slightly higher under the more recent protocol in the first 3\u2009years but no difference is estimated in the long period [survival difference at 5\u2009years (95% confidence interval) = 0.1% (\u22120.97%; 1.13%)]. Both protocols would allow reducing the event rate by 12\u201313% if there was no abandonment of treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Using IPTC weighting, we found a similar potential effect of the two treatment protocols if the imbalance due to the different distribution of potential confounders and to abandonment of therapy was removed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ije\/dyab150","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T19:11:33Z","timestamp":1625598693000},"page":"314-323","source":"Crossref","is-referenced-by-count":7,"title":["A causal inference approach to compare leukaemia treatment outcome in the absence of randomization and with dependent censoring"],"prefix":"10.1093","volume":"51","author":[{"given":"Davide Paolo","family":"Bernasconi","sequence":"first","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre\u2014B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Antolini","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre\u2014B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Rossi","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre\u2014B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica Giselle","family":"Blanco-Lopez","sequence":"additional","affiliation":[{"name":"National Pediatric Oncology Unit, Guatemala City, Guatemala"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre\u2014B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per Kragh","family":"Andersen","sequence":"additional","affiliation":[{"name":"Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Grazia","family":"Valsecchi","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre\u2014B4, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"2022021817285425000_dyab150-B1","author":"Howlader","year":"2015"},{"key":"2022021817285425000_dyab150-B2","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1182\/blood-2004-04-1616","article-title":"Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children\u2019s Research Hospital","volume":"104","author":"Pui","year":"2004","journal-title":"Blood"},{"key":"2022021817285425000_dyab150-B3","doi-asserted-by":"crossref","first-page":"3742","DOI":"10.1200\/JCO.2005.00.554","article-title":"Childhood cancer survival trends in Europe: a EUROCARE Working Group study","volume":"23","author":"Gatta","year":"2005","journal-title":"J Clin Oncol"},{"key":"2022021817285425000_dyab150-B4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3322\/caac.20121","article-title":"Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths","volume":"61","author":"Siegel","year":"2011","journal-title":"CA Cancer J Clin"},{"key":"2022021817285425000_dyab150-B5","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/pbc.24420","article-title":"Children\u2019s Oncology Group\u2019s 2013 blueprint for research: acute lymphoblastic leukemia","volume":"60","author":"Hunger","year":"2013","journal-title":"Pediatr Blood Cancer"},{"key":"2022021817285425000_dyab150-B6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/ijc.2910630108","article-title":"Descriptive epidemiology of lymphoid and haemopoietic malignancies in Bangalore, India","volume":"63","author":"Nandakumar","year":"1995","journal-title":"Int J Cancer"},{"key":"2022021817285425000_dyab150-B7","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/S0140-6736(14)62038-9","article-title":"Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from population-based registries in 67 countries (CONCORD2)","volume":"385","author":"Allemani","year":"2015","journal-title":"Lancet"},{"key":"2022021817285425000_dyab150-B8","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/pbc.20245","article-title":"Delays in diagnosis and treatment of childhood cancer: where in the world are they important?","volume":"44","author":"Howard","year":"2005","journal-title":"Pediatr Blood Cancer"},{"key":"2022021817285425000_dyab150-B9","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1470-2045(11)70128-0","article-title":"Abandonment of treatment for childhood cancer: position statement of a SIOP PODC Working Group","volume":"12","author":"Mostert","year":"2011","journal-title":"Lancet Oncol"},{"key":"2022021817285425000_dyab150-B10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/mpo.1283","article-title":"Refusal, non-compliance, and abandonment of treatment in children and adolescents with cancer","volume":"38","author":"Spinetta","year":"2002","journal-title":"Med Pediatr Oncol"},{"key":"2022021817285425000_dyab150-B11","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/S0140-6736(03)14228-6","article-title":"Outcome of childhood acute lymphoblastic leukaemia in resource-poor countries","volume":"362","author":"Metzger","year":"2003","journal-title":"Lancet Oncol"},{"key":"2022021817285425000_dyab150-B12","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1002\/ijc.24534","article-title":"Prevalence and predictors of abandonment of therapy among children with cancer in El Salvador","volume":"125","author":"Bonilla","year":"2009","journal-title":"Int J Cancer"},{"key":"2022021817285425000_dyab150-B13","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1002\/pbc.25060","article-title":"Measurement of socio-economic status in families of children with cancer in Guatemala","volume":"61","author":"De Pernillo","year":"2014","journal-title":"Pediatr Blood Cancer"},{"key":"2022021817285425000_dyab150-B14","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1002\/pbc.24377","article-title":"Nutritional status of children during treatment for acute lymphoblastic leukemia in Guatemala","volume":"60","author":"Antillon","year":"2013","journal-title":"Pediatr Blood Cancer"},{"key":"2022021817285425000_dyab150-B15","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ejca.2011.06.006","article-title":"Nutritional status at diagnosis is related to clinical outcomes in children and adolescents with cancer: a perspective from Central America","volume":"48","author":"Sala","year":"2012","journal-title":"Eur J Cancer"},{"key":"2022021817285425000_dyab150-B16","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1002\/pbc.21127","article-title":"The problem of treatment abandonment in children from developing countries with cancer","volume":"49","author":"Arora","year":"2007","journal-title":"Pediatr Blood Cancer"},{"key":"2022021817285425000_dyab150-B17","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/pbc.24802","article-title":"Asociacion de Hemato-Oncologa Pediatrica de Centro America (AHOPCA ): a model for sustainable development in pediatric oncology","volume":"61","author":"Barr","year":"2014","journal-title":"Pediatr Blood Cancer"},{"key":"2022021817285425000_dyab150-B18","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/978-1-4757-1229-2_14","volume-title":"AIDS Epidemiology Methodological Issues.","author":"Robins","year":"1992"},{"key":"2022021817285425000_dyab150-B19","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/j.0006-341X.2000.00779.x","article-title":"Correcting for noncompliance and dependent censoring in an AIDS clinical trial with inverse probability of censoring weighted (IPCW) log-rank tests","volume":"56","author":"Robins","year":"2000","journal-title":"Biometrics"},{"key":"2022021817285425000_dyab150-B20","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1097\/00001648-200009000-00011","article-title":"Marginal structural models and causal inference in epidemiology","volume":"1","author":"Robins","year":"2000","journal-title":"Epidemiology"},{"key":"2022021817285425000_dyab150-B21","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/00001648-200009000-00012","article-title":"Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men","volume":"11","author":"Hern\u00e1n","year":"2000","journal-title":"Epidemiology"},{"key":"2022021817285425000_dyab150-B22","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/cncr.27846","article-title":"Outcome of children treated for relapsed acute lymphoblastic leukemia in Central America","volume":"119","author":"Marjerrison","year":"2013","journal-title":"Cancer"},{"key":"2022021817285425000_dyab150-B23","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/pbc.24911","article-title":"Treatment of childhood acute lymphoblastic leukemia in Central America: a lower-middle income countries experience","volume":"61","author":"Navarrete","year":"2014","journal-title":"Pediatr Blood Cancer"},{"key":"2022021817285425000_dyab150-B24","volume-title":"Analysing Survival Data from Clinical Trials and Observational Studies","author":"Marubini","year":"1995"},{"key":"2022021817285425000_dyab150-B25","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/aje\/kwp436","article-title":"Invited commentary: positivity in practice","volume":"171","author":"Westreich","year":"2010","journal-title":"Am J Epidemiol"},{"key":"2022021817285425000_dyab150-B26","volume-title":"Causal Inference: What If","author":"Hern\u00e1n","year":"2020"},{"key":"2022021817285425000_dyab150-B27","volume-title":"Dynamic Regression Models for Survival Data","author":"Martinussen","year":"2006"},{"key":"2022021817285425000_dyab150-B28","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cmpb.2003.10.004","article-title":"Adjusted survival curves with inverse probability weights","volume":"75","author":"Cole","year":"2004","journal-title":"Comput Methods Programs Biomed"},{"key":"2022021817285425000_dyab150-B29","volume-title":"R: A Language and Environment for Statistical Computing","year":"2019"},{"key":"2022021817285425000_dyab150-B30","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1177\/1740774518806311","article-title":"Generalizing the per-protocol treatment effect: the case of ACTG A5095","volume":"16","author":"Lu","year":"2019","journal-title":"Clin Trials"},{"key":"2022021817285425000_dyab150-B31","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.0006-341X.2002.00510.x","article-title":"A frailty model for informative censoring","volume":"58","author":"Huang","year":"2002","journal-title":"Biometrics"},{"key":"2022021817285425000_dyab150-B32","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1111\/j.1541-0420.2008.00986.x","article-title":"Regression survival analysis with an assumed copula for dependent censoring: a sensitivity analysis approach","volume":"64","author":"Huang","year":"2008","journal-title":"Biometrics"},{"key":"2022021817285425000_dyab150-B33","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1177\/1536867X0200200401","article-title":"Using Aalen\u2019s linear hazards model to investigate time-varying effects in the proportional hazards regression model","volume":"2","author":"Hosmer","year":"2002","journal-title":"Stata J"},{"key":"2022021817285425000_dyab150-B34","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12874-016-0253-9","article-title":"Inverse probability weighting to estimate causal effect of a singular phase in a multiphase randomized clinical trial for multiple myeloma","volume":"16","author":"Pezzi","year":"2016","journal-title":"BMC Med Res Methodol"},{"key":"2022021817285425000_dyab150-B35","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1056\/NEJMsm1605385","article-title":"Per-protocol analyses of pragmatic trials","volume":"377","author":"Hern\u00e1n","year":"2017","journal-title":"N Engl J Med"}],"container-title":["International Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ije\/article-pdf\/51\/1\/314\/42555495\/dyab150.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ije\/article-pdf\/51\/1\/314\/42555495\/dyab150.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T17:30:17Z","timestamp":1645205417000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ije\/article\/51\/1\/314\/6345861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,9]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,8,9]]},"published-print":{"date-parts":[[2022,2,18]]}},"URL":"https:\/\/doi.org\/10.1093\/ije\/dyab150","relation":{},"ISSN":["0300-5771","1464-3685"],"issn-type":[{"value":"0300-5771","type":"print"},{"value":"1464-3685","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2,1]]},"published":{"date-parts":[[2021,8,9]]}}}