{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T21:44:49Z","timestamp":1774993489251,"version":"3.50.1"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin\u2019s lymphoma of increasing prevalence in Japan. However, patients with relapsed or refractory disease to first line treatment (rrDLBCL) have been found to shoulder greater economic burden and have poor survival with subsequent lines of therapy. The relative impact of individual patient attributes on total medical cost among patients with rrDLBCL receiving second or third line (2L\/3L) therapy was assessed. Structural equation modelling was used to identify potential cost drivers of total medical costs incurred by treatment and procedures in a Japanese retrospective claims database. From the database, rrDLBCL patients on 2L or 3L of treatment were grouped into respective cohorts. The mean [median] (SD) total medical cost of care for the 2L cohort was 73,296.40 [58,223.11] (58,409.79) US dollars (USD) and 75,238.35 [60,477.31] (59,583.66) USD for the 3L cohort. The largest total effect on medical cost in both cohorts was length of hospital stay (LOS) (\u03b2: 0.750 [95%CI: 0.728, 0.772] vs \u03b2: 0.762 [95%CI: 0.729, 0.794]). Length of hospital stay and potential heart disease complications due to line of treatment were the primary drivers of total cost for patients who had received at least 2L or 3L therapy for rrDLBCL.<\/jats:p>","DOI":"10.1371\/journal.pone.0269169","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T17:31:31Z","timestamp":1653672691000},"page":"e0269169","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cost drivers associated with diffuse large B-cell lymphoma (DLBCL) in Japan: A structural equation model (SEM) analysis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-8778","authenticated-orcid":true,"given":"Saaya","family":"Tsutsu\u00e9","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-8088","authenticated-orcid":true,"given":"Shinichi","family":"Makita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingbo","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"issue":"4","key":"pone.0269169.ref001","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/bjh.12659","article-title":"Differences in incidence and trends of haematological malignancies in Japan and the United States","volume":"164","author":"D Chihara","year":"2014","journal-title":"Br J Haematol"},{"issue":"4","key":"pone.0269169.ref002","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s12185-018-2430-6","article-title":"Epidemiology of malignant lymphoma and recent progress in research on adult T-cell leukemia\/lymphoma in Japan","volume":"107","author":"H Miyoshi","year":"2018","journal-title":"Int J Hematol"},{"issue":"25","key":"pone.0269169.ref003","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.2217\/fon-2018-0267","article-title":"Economic burden of patients with diffuse large B-cell and follicular lymphoma treated in the USA","volume":"14","author":"VA Morrison","year":"2018","journal-title":"Future Oncol"},{"issue":"5","key":"pone.0269169.ref004","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1002\/ijc.29477","article-title":"Advance and stagnation in the treatment of patients with lymphoma and myeloma: Analysis using population-based cancer registry data in Japan from 1993 to 2006","volume":"137","author":"D Chihara","year":"2015","journal-title":"Int J Cancer"},{"issue":"36","key":"pone.0269169.ref005","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1200\/JCO.2012.41.9416","article-title":"Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma","volume":"30","author":"C Gisselbrecht","year":"2012","journal-title":"J Clin Oncol"},{"issue":"6","key":"pone.0269169.ref006","doi-asserted-by":"crossref","first-page":"650","DOI":"10.6004\/jnccn.2019.0029","article-title":"NCCN Guidelines Insights: B-Cell Lymphomas, Version 3.2019","volume":"17","author":"AD Zelenetz","year":"2019","journal-title":"J Natl Compr Canc Netw"},{"issue":"16","key":"pone.0269169.ref007","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1182\/blood-2017-03-769620","article-title":"Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study","volume":"130","author":"M Crump","year":"2017","journal-title":"Blood"},{"issue":"10","key":"pone.0269169.ref008","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1002\/ajh.23524","article-title":"Outcomes of patients with relapsed\/refractory diffuse large B-cell lymphoma with progression of lymphoma after autologous stem cell transplantation in the rituximab era","volume":"88","author":"SJ Nagle","year":"2013","journal-title":"Am J Hematol"},{"issue":"9","key":"pone.0269169.ref009","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1634\/theoncologist.2018-0490","article-title":"Direct Costs Associated with Relapsed Diffuse Large B-Cell Lymphoma Therapies","volume":"24","author":"A Purdum","year":"2019","journal-title":"Oncologist"},{"issue":"12","key":"pone.0269169.ref010","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1080\/10428194.2018.1459613","article-title":"Costs of relapsed diffuse large B-cell lymphoma among Medicare patients","volume":"59","author":"S Huntington","year":"2018","journal-title":"Leuk Lymphoma"},{"issue":"8","key":"pone.0269169.ref011","doi-asserted-by":"crossref","first-page":"e0237509","DOI":"10.1371\/journal.pone.0237509","article-title":"Nationwide claims database analysis of treatment patterns, costs and survival of Japanese patients with diffuse large B-cell lymphoma","volume":"15","author":"S Tsutsu\u00e9","year":"2020","journal-title":"PLoS One"},{"issue":"1","key":"pone.0269169.ref012","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s12032-017-1075-2","article-title":"Chemotherapy and echocardiographic indices in patients with non-Hodgkin lymphoma: the ONCO-ECHO study","volume":"35","author":"K Mizia-Stec","year":"2017","journal-title":"Med Oncol"},{"issue":"1","key":"pone.0269169.ref013","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.kint.2019.01.027","article-title":"Clinicopathological spectrum of renal parenchymal involvement in B-cell lymphoproliferative disorders","volume":"96","author":"V Javaugue","year":"2019","journal-title":"Kidney Int"},{"key":"pone.0269169.ref014","first-page":"7960907","article-title":"Pretreatment Liver Injury Predicts Poor Prognosis of DLBCL Patients","volume":"2017","author":"Q Shi","year":"2017","journal-title":"Mediators Inflamm"},{"issue":"173","key":"pone.0269169.ref015","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/aje\/kwq433","article-title":"Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries","volume":"15","author":"H Quan","year":"2011","journal-title":"Am J Epidemiol"},{"issue":"33","key":"pone.0269169.ref016","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.2217\/fon-2021-0400","article-title":"Economic burden in treated Japanese patients with relapsed\/refractory large B-cell lymphoma","volume":"17","author":"S Tsutsu\u00e9","year":"2021","journal-title":"Future Oncol"},{"key":"pone.0269169.ref017","unstructured":"Bank of Japan. Foriegn Exchange Rates (Daily) 2020 [https:\/\/www.boj.or.jp\/en\/statistics\/market\/forex\/fxdaily\/index.htm\/."},{"key":"pone.0269169.ref018","unstructured":"Statistical Bureau of Japan. 2015-Base Explanation of the Consumer Price Index [https:\/\/www.stat.go.jp\/english\/data\/cpi\/1589.html."},{"key":"pone.0269169.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v048.i02","article-title":"lavaan: an R package for structural equation modeling","volume":"48","author":"Y. Rosseel","year":"2012","journal-title":"J Stat Softw"},{"issue":"4","key":"pone.0269169.ref020","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.afos.2017.10.002","article-title":"Understanding the factors associated with initiation and adherence of osteoporosis medication in Japan: An analysis of patient perceptions","volume":"3","author":"H Orimo","year":"2017","journal-title":"Osteoporos Sarcopenia"},{"key":"pone.0269169.ref021","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/BF02293875","article-title":"Some contributions to efficient statistics in strucutral models: Specification and estimation of moment structures","volume":"48","author":"PM Bentler","year":"1983","journal-title":"Psychometricka"},{"issue":"2","key":"pone.0269169.ref022","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1080\/10705511.2018.1505522","article-title":"More Robust Standard Error and Confidence Interval for SEM Parameters Given Incorrect Model and Nonnormal Data","volume":"26","author":"K. Lai","year":"2019","journal-title":"Struct Equ Modeling"},{"issue":"3","key":"pone.0269169.ref023","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s10461-006-9150-2","article-title":"Mediational analysis in HIV\/AIDS research: estimating multivariate path analytic models in a structural equation modeling framework","volume":"11","author":"A Bryan","year":"2007","journal-title":"AIDS Behav"},{"key":"pone.0269169.ref024","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.conctc.2017.06.005","article-title":"Comparison of methods for the analysis of relatively simple mediation models","volume":"7","author":"JJM Rijnhart","year":"2017","journal-title":"Contemp Clin Trials Commun"},{"issue":"1","key":"pone.0269169.ref025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10705519909540118","article-title":"Cutoff criteria for fit indexes in covariance structure analysis: Conventional criteria versus new alternatives","volume":"6","author":"L Hu","year":"1999","journal-title":"Struct Equ Modeling"},{"key":"pone.0269169.ref026","unstructured":"Rosseel Y, Jorgensen TD, Rockwood N, Oberski D, Byrnes J, Vanbrabant L, et al. Package \u2018lavaan\u2019: CRAN; 2021 [https:\/\/cran.r-project.org\/web\/packages\/lavaan\/lavaan.pdf."},{"issue":"29","key":"pone.0269169.ref027","doi-asserted-by":"crossref","first-page":"e11491","DOI":"10.1097\/MD.0000000000011491","article-title":"Hospitalization costs and length of stay of Japanese children with respiratory syncytial virus: A structural equation modeling approach","volume":"97","author":"R Sruamsiri","year":"2018","journal-title":"Medicine (Baltimore)"},{"issue":"2","key":"pone.0269169.ref028","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3960\/jslrt.56.100","article-title":"Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma","volume":"56","author":"E. Kondo","year":"2016","journal-title":"J Clin Exp Hematop"},{"key":"pone.0269169.ref029","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1182\/blood-2019-123664","article-title":"Treatment Patterns and Outcomes in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Experience from a Single UK Centre","volume":"134","author":"J Radford","year":"2019","journal-title":"Blood"},{"issue":"2","key":"pone.0269169.ref030","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1524-4733.2007.00227.x","article-title":"Costs associated with diffuse large B-cell lymphoma patient treatment in a Canadian integrated cancer care center","volume":"11","author":"RC Lee","year":"2008","journal-title":"Value Health"},{"issue":"1","key":"pone.0269169.ref031","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1349-7006.2007.00662.x","article-title":"Phase II study of a salvage regimen using cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab in patients with relapsed or refractory B-cell non-Hodgkin\u2019s lymphoma","volume":"99","author":"Y Oki","year":"2008","journal-title":"Cancer Sci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269169","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T09:04:56Z","timestamp":1700643896000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269169"}},"subtitle":[],"editor":[{"given":"Khurshid","family":"Alam","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,5,27]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0269169","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,27]]}}}