{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:04:35Z","timestamp":1773763475482,"version":"3.50.1"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic obstructive pulmonary disease (COPD) is a group of progressive lung diseases, leading to increased healthcare use, expenditures, and risk of mortality. In June 2024, the Institute for Clinical and Economic Review (ICER) released a traditional cost-effectiveness analysis (CEA) of ensifentrine\u00a0+\u00a0background maintenance therapy (BMT) for the treatment of moderate-to-severe COPD. This study\u2019s objective is to analyze the sensitivity of ICER\u2019s traditional CEA methods to\u00a0various adjustments to their model, including Generalized Cost-Effectiveness Analysis (GCEA) elements such as generalized risk-adjusted cost-effectiveness (GRACE), dynamic pricing, and stacked cohorts. A Markov model simulated the value of ensifentrine\u00a0+\u00a0BMT relative to BMT only for treating moderate-to-severe COPD, with patients transitioning across health states defined by levels of lung functionality. We estimated the annual value-based prices (VBPs) and incremental cost-effectiveness ratios of ensifentrine\u00a0+\u00a0BMT relative to BMT using traditional CEA\u00a0and GCEA methods, including multiple scenario analyses. The VBP of ensifentrine\u00a0+\u00a0BMT is estimated at $61,008 when all GCEA elements are included. Relative to the traditional CEA static pricing scenario, GRACE increases VBPs by roughly 10\u202f%, while dynamic pricing increases VBPs by 7\u201311\u202f%. Stacked cohorts with dynamic pricing increases VBPs by 86\u2013170\u202f%. When including GCEA elements and adjustments to better reflect real-world COPD clinical pathways, ensifentrine\u00a0+\u00a0BMT is cost-effective below an annual price of $61,000\u202fat a willingness-to-pay of $150,000 per quality-adjusted life-year.<\/jats:p>","DOI":"10.1515\/fhep-2025-0007","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T03:56:57Z","timestamp":1763611017000},"page":"1-20","source":"Crossref","is-referenced-by-count":0,"title":["Estimating the Value of Ensifentrine in Addition to Background Maintenance Therapy for the Treatment of Chronic Obstructive Pulmonary Disease"],"prefix":"10.1515","volume":"28","author":[{"given":"Stella M.","family":"Arndorfer","sequence":"first","affiliation":[{"name":"EntityRisk , Princeton , NJ , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elmar R.","family":"Alizadeh","sequence":"additional","affiliation":[{"name":"EntityRisk , Princeton , NJ , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavita","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Verona Pharma Plc , Raleigh , NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Jones","sequence":"additional","affiliation":[{"name":"Verona Pharma Plc , Raleigh , NC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston , MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"2026031707001914876_j_fhep-2025-0007_ref_001","doi-asserted-by":"crossref","unstructured":"Agusti, A., B. R. Celli, G. J. Criner, D. Halpin, A. Anzueto, P. Barnes, et al.. 2023. \u201cGlobal Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary.\u201d American Journal of Respiratory and Critical Care Medicine 207 (7): 819\u201337. https:\/\/doi.org\/10.1164\/rccm.202301-0106PP.","DOI":"10.1164\/rccm.202301-0106PP"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_002","unstructured":"American Lung Association. 2023. \u201cCOPD Trends Brief. Trends in Lung Disease.\u201d https:\/\/www.lung.org\/research\/trends-in-lung-disease\/copd-trends-brief."},{"key":"2026031707001914876_j_fhep-2025-0007_ref_003","doi-asserted-by":"crossref","unstructured":"Anzueto, A., I. Z. Barjaktarevic, T. M. Siler, T. Rheault, T. Bengtsson, K. Rickard, et al.. 2023. \u201cEnsifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, placebo-controlled, Multicenter Phase III Trials (The ENHANCE Trials).\u201d American Journal of Respiratory and Critical Care Medicine 208 (4): 406\u201316. https:\/\/doi.org\/10.1164\/rccm.202306-0944OC.","DOI":"10.1164\/rccm.202306-0944OC"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_004","doi-asserted-by":"crossref","unstructured":"Arias, E., J. Xu, and K. Kochanek. 2023. \u201cUnited\u00a0States Life Tables, 2021.\u201d National Vital Statistics Reports 72 (12): 1\u201364. https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/38048433.","DOI":"10.15620\/cdc:132418"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_005","doi-asserted-by":"crossref","unstructured":"Bafadhel, M., S. Peterson, M. A. De Blas, P. M. Calverley, S. I. Rennard, K. Richter, et al.. 2018. \u201cPredictors of Exacerbation Risk and Response to Budesonide in Patients with Chronic Obstructive Pulmonary Disease: A Post-hoc Analysis of Three Randomised Trials.\u201d Lancet Respiratory Medicine 6 (2): 117\u201326. https:\/\/doi.org\/10.1016\/S2213-2600(18)30006-7.","DOI":"10.1016\/S2213-2600(18)30006-7"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_006","doi-asserted-by":"crossref","unstructured":"Bogart, M. R., S. D. Hopson, H. C. Shih, R. H. Stanford, and A. D. Coutinho. 2020. \u201cCOPD Exacerbation Costs in the IMPACT Study: A Within-Trial Analysis.\u201d American Journal of Managed Care 26 (5): e150\u2013e154. https:\/\/doi.org\/10.37765\/ajmc.2020.43157.","DOI":"10.37765\/ajmc.2020.43157"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_007","doi-asserted-by":"crossref","unstructured":"Capel, M., M. Mareque, C. J. Alvarez, L. Lindner, and I. Oyaguez. 2018. \u201cCost-Effectiveness of Fixed-Dose Combinations Therapies for Chronic Obstructive Pulmonary Disease Treatment.\u201d Clinical Drug Investigation 38 (7): 611\u201320. https:\/\/doi.org\/10.1007\/s40261-018-0646-0.","DOI":"10.1007\/s40261-018-0646-0"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_008","doi-asserted-by":"crossref","unstructured":"Chen, S., M. Small, L. Lindner, and X. Xu. 2018. \u201cSymptomatic Burden of COPD for Patients Receiving Dual or Triple Therapy.\u201d International Journal of Chronic Obstructive Pulmonary Disease 13: 1365\u201376. https:\/\/doi.org\/10.2147\/COPD.S163717.","DOI":"10.2147\/COPD.S163717"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_009","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2025. Global Strategy for Prevention, Diagnosis and Management of COPD: 2025 Report. Bethesda, MD, USA: Bethesda: GOLD. https:\/\/goldcopd.org\/2025-gold-report\/."},{"key":"2026031707001914876_j_fhep-2025-0007_ref_010","doi-asserted-by":"crossref","unstructured":"Hahn, B., R. H. Stanford, A. Goolsby Hunter, B. Essoi, J. White, and R. Ray. 2019. \u201cPatient-Reported Burden of Illness in a Prevalent COPD Population Treated with Long-Acting Muscarinic Antagonist Monotherapy: A Claims-Linked Patient Survey Study.\u201d Pulmonary Therapeutics 5 (1): 69\u201380. https:\/\/doi.org\/10.1007\/s41030-019-0091-0.","DOI":"10.1007\/s41030-019-0091-0"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_011","doi-asserted-by":"crossref","unstructured":"Helland, Eric, and Seth A. Seabury. 2016. Are Settlements in Patent Litigation Collusive? : Evidence from Paragraph IV Challenges. NBER Working Paper Series No. 22194. Cambridge: National Bureau of Economic Research.","DOI":"10.3386\/w22194"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_012","doi-asserted-by":"crossref","unstructured":"Lakdawalla, D. N., and C. E. Phelps. 2021. \u201cHealth Technology Assessment with Diminishing Returns to Health: The Generalized Risk-Adjusted Cost-Effectiveness (GRACE) Approach.\u201d Value in Health 24 (2): 244\u20139. https:\/\/doi.org\/10.1016\/j.jval.2020.10.003.","DOI":"10.1016\/j.jval.2020.10.003"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_013","doi-asserted-by":"crossref","unstructured":"Lakdawalla, D. N., J.\u00a0A. Doshi, L. P. GarrisonJr., C. E. Phelps, A. Basu, and P. M. Danzon. 2018. \u201cDefining Elements of Value in Health Care-A Health Economics Approach: An ISPOR Special Task Force Report [3].\u201d Value in Health 21 (2): 131\u20139. https:\/\/doi.org\/10.1016\/j.jval.2017.12.007.","DOI":"10.1016\/j.jval.2017.12.007"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_014","doi-asserted-by":"crossref","unstructured":"Lee, J.\u00a0H., Y. H. Park, D. R. Kang, S. J. Lee, M. K. Lee, S. H. Kim, et al.. 2020. \u201cRisk of Pneumonia Associated with Inhaled Corticosteroid in Patients with Chronic Obstructive Pulmonary Disease: A Korean Population-based Study.\u201d International Journal of Chronic Obstructive Pulmonary Disease 15: 3397\u2013406. https:\/\/doi.org\/10.2147\/COPD.S286149.","DOI":"10.2147\/COPD.S286149"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_015","unstructured":"Lin, G., M. D. Whittington, A. Wright, A. McKenna, M. Richardson, and D. M. Rind. 2024. \u201cEnsifentrine for the Treatment of Chronic Obstructive Pulmonary Disease: Effectiveness and Value.\u201d Institute for Clinical and Economic Review. https:\/\/icer.org\/assessment\/copd-2024\/."},{"key":"2026031707001914876_j_fhep-2025-0007_ref_016","doi-asserted-by":"crossref","unstructured":"Lin, C. H., J.\u00a0D. Campbell, J. Motyka, and J.\u00a0T. Cohen. 2025. \u201cUS Drug Pricing Patterns Before Loss of Exclusivity.\u201d Value in Health 28 (6): 907\u201314. https:\/\/doi.org\/10.1016\/j.jval.2025.03.008.","DOI":"10.1016\/j.jval.2025.03.008"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_017","doi-asserted-by":"crossref","unstructured":"Mannino, D. M., M. H. Roberts, D. W. Mapel, Q. Zhang, O. Lunacsek, S. Grabich, et al.. 2024. \u201cNational and Local Direct Medical Cost Burden of COPD in the United\u00a0States from 2016 to 2019 and Projections Through 2029.\u201d Chest 165 (5): 1093\u2013106. https:\/\/doi.org\/10.1016\/j.chest.2023.11.040.","DOI":"10.1016\/j.chest.2023.11.040"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_018","unstructured":"McCormick, B. 2024. \u201cFDA Approves Ensifentrine for Maintenance Treatment of Adult Patients with COPD.\u201d American Journal of Managed Care. https:\/\/www.ajmc.com\/view\/fda-approves-ensifentrine-for-maintenance-treatment-of-adult-patients-with-copd."},{"key":"2026031707001914876_j_fhep-2025-0007_ref_019","doi-asserted-by":"crossref","unstructured":"McQueen, R. B., K. E. Anderson, J.\u00a0F. Levy, and J.\u00a0J. Carlson. 2023. \u201cIncorporating Dynamic Pricing in Cost-Effectiveness Analysis: Are Known Unknowns Valuable?\u201d PharmacoEconomics 41 (3): 321\u20137. https:\/\/doi.org\/10.1007\/s40273-022-01230-x.","DOI":"10.1007\/s40273-022-01230-x"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_020","doi-asserted-by":"crossref","unstructured":"Moretz, C., B. Hahn, J. White, A. Goolsby Hunter, B. Essoi, C. Elliott, et al.. 2020. \u201cSymptom Burden and GOLD Classification in Medicare Advantage Patients with COPD Initiating Umeclidinium\/Vilanterol or Fluticasone Propionate\/Salmeterol Therapy.\u201d International Journal of Chronic Obstructive Pulmonary Disease 15: 2715\u201325. https:\/\/doi.org\/10.2147\/COPD.S265037.","DOI":"10.2147\/COPD.S265037"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_021","doi-asserted-by":"crossref","unstructured":"Padula, W. V., and P. Kolchinsky. 2024. \u201cCan Generalized Cost-Effectiveness Analysis Leverage Meaningful Use of Novel Value Elements in Pharmacoeconomics to Inform Medicare Drug Price Negotiation?\u201d Value in Health 27 (8): 1100\u20137. https:\/\/doi.org\/10.1016\/j.jval.2024.04.013.","DOI":"10.1016\/j.jval.2024.04.013"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_022","doi-asserted-by":"crossref","unstructured":"Rajagopalan, K., L. Bloudek, J. Marvel, C. Dembek, and A. Kavati. 2018. \u201cCost-Effectiveness of Twice-daily Indacaterol\/glycopyrrolate Inhalation Powder for the Treatment of Moderate to Severe COPD in the US.\u201d International Journal of Chronic Obstructive Pulmonary Disease 13: 3867\u201377. https:\/\/doi.org\/10.2147\/COPD.S177097.","DOI":"10.2147\/COPD.S177097"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_023","doi-asserted-by":"crossref","unstructured":"Ramagopalan, S. V., J. Diaz, G. Mitchell, L. P. GarrisonJr., and P. Kolchinsky. 2024. \u201cIs the Price Right? Paying for Value Today to Get More Value Tomorrow.\u201d BMC Medicine 22 (1): 45. https:\/\/doi.org\/10.1186\/s12916-024-03262-w.","DOI":"10.1186\/s12916-024-03262-w"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_024","doi-asserted-by":"crossref","unstructured":"Sanders, G. D., P. J. Neumann, A. Basu, D. W. Brock, D. Feeny, M. Krahn, et al.. 2016. \u201cRecommendations for Conduct, Methodological Practices, and Reporting of cost-effectiveness Analyses: Second Panel on Cost-Effectiveness in Health and Medicine.\u201d JAMA 316 (10): 1093\u2013103. https:\/\/doi.org\/10.1001\/jama.2016.12195.","DOI":"10.1001\/jama.2016.12195"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_025","doi-asserted-by":"crossref","unstructured":"Shah, C. H., R. M. Reed, L. Wastila, E. Onukwugha, M. Gopalakrishnan, and Z. Zafari. 2023. \u201cDirect Medical Costs of COPD in the USA: An Analysis of the Medical Expenditure Panel Survey 2017-2018.\u201d Applied Health Economics and Health Policy 21 (6): 915\u201324. https:\/\/doi.org\/10.1007\/s40258-023-00814-8.","DOI":"10.1007\/s40258-023-00814-8"},{"key":"2026031707001914876_j_fhep-2025-0007_ref_026","doi-asserted-by":"crossref","unstructured":"Sharafkhaneh, A., A. M. Spiegelman, K. Main, S. Tavakoli-Tabasi, C. Lan, and D. Musher. 2017. \u201cMortality in Patients Admitted for Concurrent COPD Exacerbation and Pneumonia.\u201d COPD: Journal of Chronic Obstructive Pulmonary Disease 14 (1): 23\u20139. https:\/\/doi.org\/10.1080\/15412555.2016.1220513.","DOI":"10.1080\/15412555.2016.1220513"}],"container-title":["Forum for Health Economics and Policy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/fhep-2025-0007\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/fhep-2025-0007\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:11:06Z","timestamp":1773756666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/fhep-2025-0007\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,1]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,11,21]]},"published-print":{"date-parts":[[2025,12,1]]}},"alternative-id":["10.1515\/fhep-2025-0007"],"URL":"https:\/\/doi.org\/10.1515\/fhep-2025-0007","relation":{},"ISSN":["1558-9544"],"issn-type":[{"value":"1558-9544","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,1]]}}}