Gail Prileszky

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial.

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 womens 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 womens 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 womens 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.

Mirena coil for heavy menstrual bleeding.

In a recent editorial, Miriam Santer1 highlights what little we know about quality of life and patient satisfaction following treatment for heavy menstrual bleeding. She points in particular to the paucity of relevant data comparing the levonorgestrel-releasing intrauterine system (LNG-IUS or Mirena®) with other medical treatments. Therefore, we agree that the recommended ranking in recent NICE guidelines,2 suggesting Mirena coil as the first option for heavy menstrual bleeding, seems premature, may fail to account for patient preferences, and indeed lead to problems with concordance and therefore efficacy of treatment. We are currently seeking to address some of this evidence gap in ECLIPSE, a large, randomised controlled trial assessing clinical effectiveness and cost-effectiveness of the LNG-IUS versus standard medical treatments for initial management of heavy menstrual bleeding in primary care and gynaecology settings (www.eclipse.bham.ac.uk). Outcomes include menorrhagia-specific and generic quality-of-life measures, and surgical interventions, with long-term follow-up at 2 and 5 years. Unsurprisingly, we have found recruitment particularly challenging because many women have a strong personal preference for one form of treatment or another. Within, and alongside, the trial we are seeking qualitative data in order to understand womens experiences of treatments including those of women with strong treatment preferences. This investigation seeks to build on work examining social factors and influences on womens perceptions of heavy menstrual bleeding and perceptions of health professionals in this context.3,4 Thus, we aim to provide evidence not only on the long-term effectiveness and cost-effectiveness of medical treatments for heavy menstrual bleeding, but also to enhance understanding of receiving treatments from womens perspectives. As Santer notes, much further research is needed to promote a more holistic approach to women experiencing this common and complex condition.