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NHMRC","award":["1170731"],"award-info":[{"award-number":["1170731"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Health Serv Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Breathlessness is a prevalent, distressing symptom in advanced respiratory disease. Proven treatments are lacking. Mirtazapine, an antidepressant, is increasingly prescribed. The placebo-controlled BETTER-B trial did not find significant clinical benefit of mirtazapine for severe breathlessness, and patient experiences were mixed. Given mirtazapine\u2019s low cost and wide availability, it is important to understand effects more broadly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a parallel cost-effectiveness analysis of mirtazapine versus placebo. BETTER-B recruited 225 adults with chronic obstructive pulmonary disease and\/or Interstitial Lung Diseases in seven countries between 2021 and 2023. We calculated quality-adjusted life years (QALYs) using EuroQoL EQ-5D-5\u00a0L and national value sets, and combined self-reported healthcare and informal care frequencies with unit costs. Primary trial endpoint was at day 56, with sensitivity analysis at day 180 (trial exit).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>In primary analysis mirtazapine reduced QALYs (-0.006 (95% confidence interval (CI): -0.012 to -0.001)) and was associated with higher total costs (+\u20ac231 (95% CI: -218 to +\u2009680)). For willingness-to-pay thresholds of \u20ac20,000-\u20ac40,000 per QALY, mirtazapine had a 1%-2% likelihood of being cost-effective. These findings were substantively unaffected by sensitivity analyses to timeframe, perspective, outcome measurement, and modelling strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Repurposing mirtazapine to treat severe breathlessness negatively impacted patient outcomes while being associated with higher formal and informal costs, and should be discouraged. Off-label prescribing of repurposed medicines without robust evidence risks unnecessary strain on healthcare systems and families. Economic evaluation within testing of repurposed medicines is important. Parallel cost-effectiveness analyses can deliver high-value information even when the efficacy trial finds no effect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12913-025-13605-9","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:21:58Z","timestamp":1762255318000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The cost of drug repurposing: parallel economic evaluation of mirtazapine for severe breathlessness in the multinational BETTER-B trial"],"prefix":"10.1186","volume":"25","author":[{"given":"Peter","family":"May","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Normand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adejoke O.","family":"Oluyase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah T.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Maddocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Costantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Bajwah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Kahnert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen T.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Currow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam J.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Krajnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Tanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Bolton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Janowiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Turola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline J.","family":"Jolley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Mather","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine","family":"Murden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Ghirotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobbie","family":"Farsides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene J.","family":"Higginson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On behalf of the BETTER-B consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"13605_CR1","unstructured":"Eurostat. 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Informed written consent was obtained from the patients prior to randomisation into the study, with the right of a participant to refuse participation without giving reasons. The participant had the right to withdraw at any time from the study without giving reasons and without prejudicing his\/her further treatment. The study was submitted to and approved by a main REC and the appropriate Site-Specific Assessor for each participating centre prior to entering patients into the study. The trial protocol, the written informed consent form, and other materials related to the participants were approved by the ethics committees at all sites [\n                      \n                      ]. The ethics committee(s) for respective participating countries were as follows: UK: NHS Health Research Authority, London Bridge Research Ethics Committee. Ireland: Ethics & Medical Research Department, St Vincent\u2019s University Hospital, Dublin. Italy: Comitato Etico dell\u2019Area Vasta Emilia Nord; Comitato Etico Fondazione Policlinico Universitario Agostino Gemelli IRCCS Universit\u00e0 Cattolica del Sacro Cuore. Germany: Ethikkommission bei der Medizinischen Fakult\u00e4t der LMU M\u00fcnchen; Ethikkommission der Medizinischen Fakult\u00e4t der Universit\u00e4t zu K\u00f6ln. Poland: Niezale\u017cna Komisja Bioetyczna ds. Bada\u0144 Naukowych, Gda\u0144ski Uniwersytet Medyczny. Australia: Western Sydney Local Health District Human Research Ethics Committee, Westmead, NSW. New Zealand: Health and Disability Ethics Committees, Ministry of Health, Wellington, NZ.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and informed consent"}},{"value":"N\/A.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1442"}}