Cost-effectiveness of sustained-release morphine for refractory breathlessness in COPD: A randomized clinical trial

  • Cornelia A. Verberkt
    Department of Health Services Research, Care and Public Health Research Institute, Faculty of Health Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200MD, Maastricht, the Netherlands
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  • Marieke H.J. van den Beuken-van Everdingen
    Centre of Expertise for Palliative Care, Maastricht University Medical Centre (MUMC+), P.O. Box 5800, 6202AZ, Maastricht, the Netherlands
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  • Carmen D. Dirksen
    Department of Clinical Epidemiology and Medical Technology Assessment, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center, P.O. Box 5800, 6202AZ, Maastricht, the Netherlands
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  • Jos M.G.A. Schols
    Department of Health Services Research, Care and Public Health Research Institute, Faculty of Health Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200MD, Maastricht, the Netherlands

    Department of Family Medicine, Care and Public Health Research Institute, P.O. Box 616, 6200MD, Maastricht University, Maastricht, the Netherlands
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  • Emiel F.M. Wouters
    Department of Research & Development, Ciro, P.O. Box 4009, 6080AA, Haelen, the Netherlands

    Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), P.O. Box 5800, 6202AZ, Maastricht, the Netherlands

    Ludwig Boltzmann Institute for Lung Health, Vienna, Austria
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  • Daisy J.A. Janssen
    Corresponding author. Department of Research & Development, Ciro, P.O. Box 4009, 6080AA, Haelen, the Netherlands.
    Department of Health Services Research, Care and Public Health Research Institute, Faculty of Health Medicine and Life Sciences, Maastricht University, P.O. Box 616, 6200MD, Maastricht, the Netherlands

    Department of Research & Development, Ciro, P.O. Box 4009, 6080AA, Haelen, the Netherlands
    Search for articles by this author
Published:February 09, 2021DOI:


      • Regular, low-dose, oral morphine improves health-related quality of life in COPD.
      • Healthcare and societal costs are improved after four weeks of morphine.
      • Therefore, regular, low-dose, oral morphine can be considered cost-effective.
      • Morphine should be considered in patients with COPD and chronic breathlessness.



      Chronic breathlessness is a frequent symptom in advanced Chronic Obstructive Pulmonary Disease (COPD) and has major impact on quality of life, daily activities and healthcare utilization. Morphine is used as palliative treatment of chronic breathlessness. The aim is to analyze cost-effectiveness of regular, low-dose morphine in patients with advanced COPD from a healthcare and societal perspective.


      In a randomized controlled trial, participants with advanced COPD were assigned to 10 mg regular, oral sustained-release morphine or placebo twice daily for four weeks. Quality of life (COPD Assessment Test; CAT), quality-adjusted life years (QALY's; EQ-5D-5L), healthcare costs, productivity, and patient and family costs were collected. Incremental cost-effectivity ratio's (ICERs) using healthcare costs and CAT scores, and incremental cost-utility ratio's (ICURs) using societal costs and QALY's were calculated.


      Data of 106 of 124 participants were analyzed, of which 50 were in the morphine group (mean [SD] age 65.4 [8.0] years; 58 [55%] male). Both ICER and ICUR indicated dominance for morphine treatment. Sensitivity analyses substantiated these results. From a healthcare perspective, the probability that morphine is cost-effective at a willingness to pay €8000 for an minimal clinically important difference of 2 points increase in CAT score is 63%. From a societal perspective, the probability that morphine is cost-effective at a willingness to pay €20,000 per QALY is 78%.


      Morphine for four weeks is cost-effective regarding the healthcare and the societal perspective. To estimate the long-term costs and effects of morphine treatment, a study of longer follow-up should be performed.

      Trial registration (NCT02429050).


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