Health Economic Evaluation of a Double-Blind, Randomised, Placebo-Controlled Trial of Low-Dose Oral Morphine (MABEL)

ObjectivesTo compare costs and health consequences and to assess the cost-effectiveness of using low-dose oral long-acting morphine in people with chronic breathlessness. DesignWithin-trial planned cost-consequences and cost-effectiveness analysis of data from a multi-site, parallel-group, double-blind, randomised, placebo-controlled trial of low-dose, long-acting morphine. Setting11 hospital outpatients across the UK. ParticipantsThose eligible to participate were consenting adults with chronic breathlessness due to long-term cardiorespiratory conditions. Intervention5-10mg twice-daily oral long-acting morphine with a blinded laxative for 56 days. Primary outcome measuresMean and standard deviation (SD) of healthcare resource use (HRU) by trial arm; mean differences and 95% confidence intervals (CI) of costs between trial arms. Secondary outcome measuresMean differences in 28- and 56-day quality-adjusted life years (QALYs based on EQ-5D), SF-6D scores, and ICECAP-SCM scores; cost-utility of long-acting morphine for chronic breathlessness. Results143 participants (75 morphine, 67 placebo) were randomised; 140 formed the modified intention-to-treat population (90% power; males 66%; mean age 70.5 [SD 9.4]). There were more inpatient and fewer outpatient services used by the morphine group versus 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 {pound}24 (95% CI: -{pound}395, {pound}552) and 0.002 (95% CI: -0.004, 0.008) QALYs. Hospitalisations were the main driver of cost differences. The corresponding incremental cost-effectiveness ratio (ICER) was {pound}12,000/QALY, with a probability of cost-effectiveness of 54% at a {pound}20,000 Willingness-to-Pay (WTP) 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%. ConclusionOral 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. ARTICLE SUMMARYO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIComprehensive collection of patient-reported health economic data in a randomised controlled trial, including three different health outcome measures relevant to people living with chronic breathlessness due to medical conditions C_LIO_LIThe parent trial intervention dosing schedule mirrored clinical practice to give a pragmatic indication of cost impacts C_LIO_LILimited interpretation of cost-effectiveness analysis due to a likely random imbalance in deaths and expensive adverse events, in a study design not primarily designed to detect differences in economic endpoints C_LIO_LITechnical challenges in analysing and estimating costs for concomitant medications C_LI