{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:49:35Z","timestamp":1788922175835,"version":"build-2803163510"},"reference-count":32,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"unspecified","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIHR Research Delivery Network"},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","award":["17\/34\/01"],"award-info":[{"award-number":["17\/34\/01"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,9,30]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To compare costs and health consequences and to assess the cost-effectiveness of using low-dose oral long-acting morphine in people with chronic breathlessness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Within-trial planned cost-consequences and cost-effectiveness analysis of data from a multisite, parallel-group, double-blind, randomised, placebo-controlled trial of low-dose, long-acting morphine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>11 hospital outpatients across the UK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Consenting adults with chronic breathlessness due to long-term cardiorespiratory conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>5\u201310\u2009mg two times a day oral long-acting morphine with a blinded laxative for 56 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary outcome measures<\/jats:title>\n                    <jats:p>Mean and SD of healthcare resource use (HRU) by trial arm; mean differences and 95% CI of costs between trial arms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Secondary outcome measures<\/jats:title>\n                    <jats:p>Mean differences in 28- and 56-day quality-adjusted life years (QALYs based on EuroQol five-dimension five-level score), Short Form-six dimensional scores and ICEpop CAPability-Supportive Care Measure scores; cost-utility of long-acting morphine for chronic breathlessness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>143 participants (75 morphine and 67 placebo) were randomised; 140 (90% power, males 66%, mean age 70.5 (SD 9.4)) formed the modified intention-to-treat population (participants receiving at least one dose of study medication). There were more inpatient and fewer outpatient services used by the morphine group versus the placebo. In the base-case analysis at 56 days, long-acting morphine was associated with similar mean per-patient costs and QALYs. There was an increase of \u00a324 (95% CI \u2212\u00a3395 to \u00a3552) and 0.002 (95% CI \u22120.004 to 0.008) QALYs. Hospitalisations were the main driver of cost differences. The corresponding incremental cost-effectiveness ratio was \u00a312 000\/QALY, with a probability of cost-effectiveness of 54% at a \u00a320 000 willingness-to-pay threshold. In the scenario analysis that excluded costs of adverse events considered unrelated to long-acting morphine by site investigators and researchers, the probability of cost-effectiveness increased to 73%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oral morphine for chronic breathlessness is likely to be a cost-effective intervention provided adverse events are minimised, but the effect on outcome is small and cautious interpretation is warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"nct\" xlink:href=\"NCT87329095\">NCT87329095<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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