Laura Gennard

A randomised controlled trial of Outpatient versus inpatient Polyp Treatment (OPT) for abnormal uterine bleeding.

BACKGROUND Uterine polyps cause abnormal bleeding in women and conventional practice is to remove them in hospital under general anaesthetic. Advances in technology make it possible to perform polypectomy in an outpatient setting, yet evidence of effectiveness is limited. OBJECTIVES To test the hypothesis that in women with abnormal uterine bleeding (AUB) associated with benign uterine polyp(s), outpatient polyp treatment achieved as good, or no more than 25% worse, alleviation of bleeding symptoms at 6 months compared with standard inpatient treatment. The hypothesis that response to uterine polyp treatment differed according to the pattern of AUB, menopausal status and longer-term follow-up was tested. The cost-effectiveness and acceptability of outpatient polypectomy was examined. DESIGN A multicentre, non-inferiority, randomised controlled trial, incorporating a cost-effectiveness analysis and supplemented by a parallel patient preference study. Patient acceptability was evaluated by interview in a qualitative study. SETTING Outpatient hysteroscopy clinics and inpatient gynaecology departments within UK NHS hospitals. PARTICIPANTS Women with AUB - defined as heavy menstrual bleeding (formerly known as menorrhagia) (HMB), intermenstrual bleeding or postmenopausal bleeding - and hysteroscopically diagnosed uterine polyps. INTERVENTIONS We randomly assigned 507 women, using a minimisation algorithm, to outpatient polypectomy compared with conventional inpatient polypectomy as a day case in hospital under general anaesthesia. MAIN OUTCOME MEASURES The primary outcome was successful treatment at 6 months, determined by the womans assessment of her bleeding. Secondary outcomes included quality of life, procedure feasibility, acceptability and cost per quality-adjusted life-year (QALY) gained. RESULTS At 6 months, 73% (166/228) of women who underwent outpatient polypectomy were successfully treated compared with 80% (168/211) following inpatient polypectomy [relative risk (RR) 0.91, 95% confidence interval (CI) 0.82 to 1.02]. The lower end of the CIs showed that outpatient polypectomy was at most 18% worse, in relative terms, than inpatient treatment, within the 25% margin of non-inferiority set at the outset of the study. By 1 and 2 years the corresponding proportions were similar producing RRs close to unity. There was no evidence that the treatment effect differed according to any of the predefined subgroups when treatments by variable interaction parameters were examined. Failure to completely remove polyps was higher (19% vs. 7%; RR 2.5, 95% CI 1.5 to 4.1) with outpatient polypectomy. Procedure acceptability was reduced with outpatient compared with inpatient polyp treatment (83% vs. 92%; RR 0.90, 95% CI 0.84 to 0.97). There were no significant differences in quality of life. The incremental cost-effectiveness ratios at 6 and 12 months for inpatient treatment were £1,099,167 and £668,800 per additional QALY, respectively. CONCLUSIONS When treating women with AUB associated with uterine polyps, outpatient polypectomy was non-inferior to inpatient polypectomy at 6 and 12 months, and relatively cost-effective. However, patients need to be aware that failure to remove a polyp is more likely with outpatient polypectomy and procedure acceptability lower. TRIAL REGISTRATION Current Controlled Trials ISRCTN 65868569. 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. 61. See the NIHR Journals Library website for further project information.

Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

Objective To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device (‘LNG-IUS’) and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial womens pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most cost-effective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial.

Adapting a trial design based on feasibility of recruitment where several treatment groups are possible and the outcome is long-term: pre-empt flexible-entry internal pilot study.

Background Endometriosis occurs when the endometrium grows in abnormal locations outside of the womb, resulting in pain and reduced quality of life. See-and-treat surgery removes endometriotic lesions but the risk of recurrence is high. A HTA commissioning call asked to evaluate the longterm (three years) effectiveness of post-operative longacting reversible contraceptives (LARCs) in preventing recurrence. A survey of gynaecologists indicated there was no consensus about which LARC (LNG-IUS or DMPA) or comparator (COCP or no treatment) should be evaluated. We designed a ‘flexible-entry’ internal pilot to assess whether a four-arm trial was feasible in light of possible strong patient preferences.