{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:36:28Z","timestamp":1791588988358,"version":"4.3.4"},"reference-count":58,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"unspecified","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Talent Project established by Chinese Pharmaceutical Association Hospital Phamacy Department","award":["CPA-Z05-ZC-2023-003"],"award-info":[{"award-number":["CPA-Z05-ZC-2023-003"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104476"],"award-info":[{"award-number":["82104476"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dawning Program of Wuhan Knowledge Innovation Special Project","award":["2023020201020501"],"award-info":[{"award-number":["2023020201020501"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,2,5]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Atezolizumab plus bevacizumab demonstrates a significant improvement in overall survival and progression-free survival compared with sorafenib in patients with unresectable hepatocellular carcinoma (HCC). The combined usage of these two medications could result in substantial consumption of resources, primarily due to their exceptionally high costs. The current study aims to evaluate the cost-effectiveness of atezolizumab plus bevacizumab as a first-line treatment for advanced HCC from the perspective of payers in developed and developing countries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A partitioned survival model was constructed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab versus sorafenib as a first-line treatment for advanced HCC. The efficacy and safety data incorporated within the model were derived from the IMbrave150 trial. Costs and utilities were extracted from published sources.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Atezolizumab plus bevacizumab versus sorafenib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome measures<\/jats:title>\n                    <jats:p>Estimates were calculated for costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER) for both treatment strategies. One-way sensitivity, probabilistic sensitivity, expected value of perfect information (EVPI), subgroup and scenario analyses were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The combination therapy of atezolizumab and bevacizumab results in an additional 0.72 life-years\/0.57 QALYs in the USA and 0.64 life-years\/0.47 QALYs in China compared with standard sorafenib treatment, although with a significant increase in costs, yielding an average ICER of US$253 247.07\/QALY in the USA and US$181 552.71\/QALY in China. The probability sensitivity analysis indicated that atezolizumab plus bevacizumab demonstrated a 13.60% likelihood of cost-effectiveness in the USA, whereas this likelihood is negligible (0%) in China. The expected value of uncertainty, as quantified by the EVPI, was estimated at approximately US$3658.41\/patient in the USA and US$0\/patient in China. The ICER was most sensitive to the cost of subsequent treatment in the USA, and most sensitive to the cost of atezolizumab in China. In scenario analyses, the atezolizumab plus bevacizumab treatment becomes favourable when the cost of atezolizumab decreases to 67.85% and 18.45% of its original price in the USA and China, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The atezolizumab plus bevacizumab is unlikely to be cost-effective compared with sorafenib for patients with unresectable HCC in the context of the USA and China. The implementation of significant reductions in drug prices may render the treatment economically viable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-094804","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T07:17:31Z","timestamp":1741331851000},"page":"e094804","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Cost-effectiveness of atezolizumab plus bevacizumab versus sorafenib as first-line therapy in unresectable hepatocellular carcinoma in the US and Chinese setting: a modelling comparison study"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct03434379","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Lulu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Outpatient Department Office, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4779-3875","authenticated-orcid":false,"given":"Qilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"2025121600553503000_15.3.e094804.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"2025121600553503000_15.3.e094804.2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12818"},{"key":"2025121600553503000_15.3.e094804.3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0279786","article-title":"First-line systemic treatment strategies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis","volume":"18","author":"wang","year":"2023","journal-title":"PLoS ONE"},{"key":"2025121600553503000_15.3.e094804.4","doi-asserted-by":"crossref","DOI":"10.1177\/17562848221140662","article-title":"First-line treatments for advanced hepatocellular carcinoma: a network meta-analysis and cost-effectiveness analysis in China and the United States","volume":"15","author":"Sun","year":"2022","journal-title":"Therap Adv Gastroenterol"},{"key":"2025121600553503000_15.3.e094804.5","doi-asserted-by":"crossref","first-page":"869960","DOI":"10.3389\/fpubh.2022.869960","article-title":"Cost-Effectiveness Analysis of Five Systemic Treatments for Unresectable Hepatocellular Carcinoma in China: An Economic Evaluation Based on Network Meta-Analysis","volume":"10","author":"Zhao","year":"2022","journal-title":"Front Public Health"},{"key":"2025121600553503000_15.3.e094804.6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.4410"},{"key":"2025121600553503000_15.3.e094804.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30207-1"},{"key":"2025121600553503000_15.3.e094804.8","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1080\/17474124.2022.2064273","article-title":"Which role for predictors of response to immune checkpoint inhibitors in hepatocellular carcinoma?","volume":"16","author":"Rizzo","year":"2022","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"2025121600553503000_15.3.e094804.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.025"},{"key":"2025121600553503000_15.3.e094804.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"2025121600553503000_15.3.e094804.11","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2021.4846","article-title":"Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib for Patients With Unresectable or Metastatic Hepatocellular Carcinoma","volume":"4","author":"Zhang","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2025121600553503000_15.3.e094804.12","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2021.0037","article-title":"Cost-effectiveness of Atezolizumab Plus Bevacizumab vs Sorafenib as First-Line Treatment of Unresectable Hepatocellular Carcinoma","volume":"4","author":"Su","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2025121600553503000_15.3.e094804.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.030"},{"key":"2025121600553503000_15.3.e094804.14","unstructured":"National Comprehensive Cancer Network Guidelines . Hepatocellular Carcinoma (version 1, 2023), Available: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/hcc.pdf"},{"key":"2025121600553503000_15.3.e094804.15","first-page":"403","article-title":"Study on Guidelines of Chinese Society of Clinical Oncology (CSCO): Hepatocellular Carcinoma (2022)","volume":"30","author":"Wang","year":"2023","journal-title":"Chinese J Bases Clin General Surg"},{"key":"2025121600553503000_15.3.e094804.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2021.11.1351"},{"key":"2025121600553503000_15.3.e094804.17","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2288-12-9","article-title":"Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves","volume":"12","author":"Guyot","year":"2012","journal-title":"BMC Med Res Methodol"},{"key":"2025121600553503000_15.3.e094804.18","doi-asserted-by":"publisher","DOI":"10.1177\/0272989X12472398"},{"key":"2025121600553503000_15.3.e094804.19","doi-asserted-by":"publisher","DOI":"10.1007\/s41669-021-00260-z"},{"key":"2025121600553503000_15.3.e094804.20","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cmpb.2013.07.021","article-title":"Mixture and non-mixture cure fraction models based on the generalized modified Weibull distribution with an application to gastric cancer data","volume":"112","author":"Martinez","year":"2013","journal-title":"Comput Methods Programs Biomed"},{"key":"2025121600553503000_15.3.e094804.21","unstructured":"National Bureau of Statistics of China, 2021. Available: http:\/\/data.stats.gov.cn\/english\/index.htm"},{"key":"2025121600553503000_15.3.e094804.22","unstructured":"FRED Economic Data . Research: Federal Reserve Bank of St Louis. Consumer Price Index for all urban consumers: medical care in U.S, 2023. Available: https:\/\/fred.stlouisfed.org\/series\/CPIMEDSL"},{"key":"2025121600553503000_15.3.e094804.23","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.790373","article-title":"Cost-Effectiveness Analysis of Camrelizumab vs. Placebo Added to Chemotherapy as First-Line Therapy for Advanced or Metastatic Esophageal Squamous Cell Carcinoma in China","volume":"11","author":"Zhang","year":"2021","journal-title":"Front Oncol"},{"key":"2025121600553503000_15.3.e094804.24","unstructured":"IBM Corporation . IBM Micromedex, Available: http:\/\/www.micromedexsolutions.com"},{"key":"2025121600553503000_15.3.e094804.25","unstructured":"Chinese Drug . Chinese Drug Price of Drug Centralized Bid Procurement, 2021. Available: https:\/\/db.yaozh.com\/yaopinzhongbiao"},{"key":"2025121600553503000_15.3.e094804.26","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1080\/14737167.2022.2079498","article-title":"Cost-effectiveness analysis of donafenib versus lenvatinib for first-line treatment of unresectable or metastatic hepatocellular carcinoma","volume":"22","author":"Meng","year":"2022","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"2025121600553503000_15.3.e094804.27","doi-asserted-by":"crossref","first-page":"562135","DOI":"10.3389\/fonc.2021.562135","article-title":"Cost-Effectiveness Analysis of Hepatic Arterial Infusion of FOLFOX Combined Sorafenib for Advanced Hepatocellular Carcinoma With Portal Vein Invasion","volume":"11","author":"Li","year":"2021","journal-title":"Front Oncol"},{"key":"2025121600553503000_15.3.e094804.28","doi-asserted-by":"crossref","first-page":"669","DOI":"10.6004\/jnccn.2018.7275","article-title":"Cost-Effectiveness of Cabozantinib in the Second-Line Treatment of Advanced Hepatocellular Carcinoma","volume":"17","author":"Soto-Perez-de-Celis","year":"2019","journal-title":"J Natl Compr Canc Netw"},{"key":"2025121600553503000_15.3.e094804.29","doi-asserted-by":"crossref","first-page":"1092385","DOI":"10.3389\/fimmu.2023.1092385","article-title":"Cost-effectiveness of sintilimab plus chemotherapy versus chemotherapy alone as first-line treatment of locally advanced or metastatic oesophageal squamous cell carcinoma","volume":"14","author":"Liu","year":"2023","journal-title":"Front Immunol"},{"key":"2025121600553503000_15.3.e094804.30","doi-asserted-by":"crossref","first-page":"e340","DOI":"10.3747\/co.23.2244","article-title":"Cost-effectiveness of pazopanib compared with sunitinib in metastatic renal cell carcinoma in Canada","volume":"23","author":"Amdahl","year":"2016","journal-title":"Curr Oncol"},{"key":"2025121600553503000_15.3.e094804.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.vhri.2020.07.580"},{"key":"2025121600553503000_15.3.e094804.32","unstructured":"Institute for Clinical and Economic Review . ICER\u2019s reference case for economic evaluations: principles and rationale, 2020. Available: https:\/\/icer.org\/wp-content\/uploads\/2020\/10\/ICER_Reference_Case_013120.pdf"},{"key":"2025121600553503000_15.3.e094804.33","doi-asserted-by":"publisher","DOI":"10.1586\/14737167.1.1.37"},{"key":"2025121600553503000_15.3.e094804.34","doi-asserted-by":"publisher","DOI":"10.1177\/0272989X9801800209"},{"key":"2025121600553503000_15.3.e094804.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2020.01.001"},{"key":"2025121600553503000_15.3.e094804.36","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jval.2020.01.004","article-title":"Value of Information Analytical Methods: Report 2 of the ISPOR Value of Information Analysis Emerging Good Practices Task Force","volume":"23","author":"Rothery","year":"2020","journal-title":"Value Health"},{"key":"2025121600553503000_15.3.e094804.37","doi-asserted-by":"crossref","DOI":"10.18637\/jss.v070.i08","article-title":"flexsurv: A Platform for Parametric Survival Modeling in R","volume":"70","author":"Jackson","year":"2016","journal-title":"J Stat Softw"},{"key":"2025121600553503000_15.3.e094804.38","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00151-0"},{"key":"2025121600553503000_15.3.e094804.39","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14795"},{"key":"2025121600553503000_15.3.e094804.40","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13050931","article-title":"First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis","volume":"13","author":"Chiang","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2025121600553503000_15.3.e094804.41","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0280442","article-title":"Cost-utility analysis of atezolizumab with bevacizumab in untreated unresectable or advanced hepatocellular carcinoma in France","volume":"18","author":"Gaugain","year":"2023","journal-title":"PLoS One"},{"key":"2025121600553503000_15.3.e094804.42","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/cac2.12110","article-title":"Atezolizumab plus bevacizumab versus sorafenib as first\u2010line treatment for unresectable hepatocellular carcinoma: a cost\u2010effectiveness analysis","volume":"40","author":"Hou","year":"2020","journal-title":"Cancer Commun"},{"key":"2025121600553503000_15.3.e094804.43","doi-asserted-by":"crossref","DOI":"10.1186\/s13561-024-00526-2","article-title":"Cost-effectiveness of immune checkpoint inhibitors as a first-line therapy for advanced hepatocellular carcinoma: a systematic review","volume":"14","author":"Gong","year":"2024","journal-title":"Health Econ Rev"},{"key":"2025121600553503000_15.3.e094804.44","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(23)02405-4","article-title":"Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial","volume":"403","author":"Oaknin","year":"2024","journal-title":"Lancet"},{"key":"2025121600553503000_15.3.e094804.45","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1001\/jamaoncol.2021.5981","article-title":"Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma","volume":"8","author":"Motzer","year":"2022","journal-title":"JAMA Oncol"},{"key":"2025121600553503000_15.3.e094804.46","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.jval.2024.07.013","article-title":"First-Line Treatment With Atezolizumab Plus Bevacizumab and Chemotherapy for US Patients With Metastatic, Persistent, or Recurrent Cervical Cancer: A Cost-Effectiveness Analysis","volume":"27","author":"Lei","year":"2024","journal-title":"Value Health"},{"key":"2025121600553503000_15.3.e094804.47","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/14737167.2024.2399246","article-title":"Cost-effectiveness of atezolizumab plus bevacizumab as first-line therapy for metastatic renal cell carcinoma","volume":"25","author":"Wang","year":"2025","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"key":"2025121600553503000_15.3.e094804.48","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1476256","article-title":"Atezolizumab plus bevacizumab and chemotherapy versus bevacizumab plus chemotherapy for metastatic cervical cancer: a cost-effectiveness analysis","volume":"15","author":"Cai","year":"2024","journal-title":"Front Pharmacol"},{"key":"2025121600553503000_15.3.e094804.49","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1481584","article-title":"Atezolizumab plus bevacizumab and chemotherapy as first-line therapy for cervical cancer: a cost-effectiveness analysis in the US","volume":"15","author":"Lin","year":"2024","journal-title":"Front Immunol"},{"key":"2025121600553503000_15.3.e094804.50","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.mayocp.2013.01.003","article-title":"The High Cost of Cancer Drugs and What We Can Do About It","volume":"88","author":"Rosamond","year":"2013","journal-title":"Mayo Clin Proc"},{"key":"2025121600553503000_15.3.e094804.51","doi-asserted-by":"crossref","DOI":"10.1186\/s40425-018-0442-7","article-title":"A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors","volume":"6","author":"Verma","year":"2018","journal-title":"J Immunother Cancer"},{"key":"2025121600553503000_15.3.e094804.52","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28961"},{"key":"2025121600553503000_15.3.e094804.53","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1405158"},{"key":"2025121600553503000_15.3.e094804.54","doi-asserted-by":"crossref","unstructured":"Dyer O . US drug prices should be tied to foreign prices to tackle \u201cglobal freeloading,\u201d says Trump. BMJ 2018;k4542. doi:10.1136\/bmj.k4542","DOI":"10.1136\/bmj.k4542"},{"key":"2025121600553503000_15.3.e094804.55","doi-asserted-by":"crossref","DOI":"10.1136\/bmjgh-2022-011535","article-title":"Improving access to medicines and beyond: the national volume-based procurement policy in China","volume":"8","author":"Zhu","year":"2023","journal-title":"BMJ Glob Health"},{"key":"2025121600553503000_15.3.e094804.56","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33326-3"},{"key":"2025121600553503000_15.3.e094804.57","doi-asserted-by":"publisher","DOI":"10.1177\/1740774506073464"},{"key":"2025121600553503000_15.3.e094804.58","doi-asserted-by":"crossref","DOI":"10.1186\/s40425-018-0440-9","article-title":"Cost-effectiveness of nivolumab plus ipilimumab as first-line therapy in advanced renal-cell carcinoma","volume":"6","author":"Wu","year":"2018","journal-title":"J Immunother Cancer"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-094804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T08:55:57Z","timestamp":1765875357000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-094804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":58,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,6]]},"published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1136\/bmjopen-2024-094804"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-094804","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]}}}