Headline
The study found that the levonorgestrel-releasing intrauterine system (LNG-IUS) leads to greater improvement compared with usual medical therapies over 2 years in women’s assessments of the effect of heavy menstrual bleeding (HMB) on their daily routine, including work, social and family life, and psychological and physical well-being. These findings were no longer significantly different at 5 years. In the primary care setting, treating HMB using the LNG-IUS costs more, but is also more effective, using the EQ-5D as the outcome, than usual medical treatment in both the short and medium term.
Abstract
Background:
Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited.
Objectives:
To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of women’s perspectives on treatment.
Design:
A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study.
Setting:
Women who presented in primary care.
Participants:
A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment.
Interventions:
LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen–progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment.
Outcome measures:
The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost–utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses.
Results:
The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI –0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women’s experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments.
Conclusions:
The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women’s assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause.
Trial registration:
Current Controlled Trials ISRCTN86566246.
Funding:
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information
Article history
The research reported in this issue of the journal was funded by the HTA programme as project number 02/06/02. The contractual start date was in November 2004. The draft report began editorial review in February 2015 and was accepted for publication in May 2015. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.
Declared competing interests of authors
Janesh K Gupta reports personal fees and non-financial support from training workshops for Ethicon, personal fees and non-financial support from Bayer, outside the submitted work. Joe Kai reports personal fees from Bayer Group for a postgraduate lecture outside the submitted work.
