Clinical and cost-effectiveness of pessary self-management versus clinic-based care for pelvic organ prolapse in women: the TOPSY RCT with process evaluation.

Background: Pelvic organ prolapse is common, causes unpleasant symptoms and negatively affects women's quality of life. In the UK, most women with pelvic organ prolapse attend clinics for pessary care. Objectives: To determine the clinical effectiveness and cost-effectiveness of vaginal pessary self-management on prolapse-specific quality of life for women with prolapse compared with clinic-based care; and to assess intervention acceptability and contextual influences on effectiveness, adherence and fidelity. Design: A multicentre, parallel-group, superiority randomised controlled trial with a mixed-methods process evaluation. Participants: Women attending UK NHS outpatient pessary services, aged ≥ 18 years, using a pessary of any type/material (except shelf, Gellhorn or Cube) for at least 2 weeks. Exclusions: women with limited manual dexterity, with cognitive deficit (prohibiting consent or self-management), pregnant or non-English-speaking. Intervention: The self-management intervention involved a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a local clinic telephone helpline number. Clinic-based care involved routine appointments determined by centres' usual practice. Allocation: Remote web-based application; minimisation was by age, pessary user type and centre. Blinding: Participants, those delivering the intervention and researchers were not blinded to group allocation. Outcomes: The patient-reported primary outcome (measured using the Pelvic Floor Impact Questionnaire-7) was prolapse-specific quality of life, and the cost-effectiveness outcome was incremental cost per quality-adjusted life-year (a specifically developed health Resource Use Questionnaire was used) at 18 months post randomisation. Secondary outcome measures included self-efficacy and complications. Process evaluation data were collected by interview, audio-recording and checklist. Analysis was by intention to treat. Results: Three hundred and forty women were randomised (self-management, n = 169; clinic-based care, n = 171). At 18 months post randomisation, 291 questionnaires with valid primary outcome data were available (self-management, n = 139; clinic-based care, n = 152). Baseline economic analysis was based on 264 participants (self-management, n = 125; clinic-based care, n = 139) with valid quality of life and resource use data. Self-management was an acceptable intervention. There was no group difference in prolapse-specific quality of life at 18 months (adjusted mean difference -0.03, 95% confidence interval -9.32 to 9.25). There was fidelity to intervention delivery. Self-management was cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, with an estimated incremental net benefit of £564.32 and an 80.81% probability of cost-effectiveness. At 18 months, more pessary complications were reported in the clinic-based care group (adjusted mean difference 3.83, 95% confidence interval 0.81 to 6.86). There was no group difference in general self-efficacy, but self-managing women were more confident in pessary self-management activities. In both groups, contextual factors impacted on adherence and effectiveness. There were no reported serious unexpected serious adverse reactions. There were 32 serious adverse events (self-management, n = 17; clinic-based care, n = 14), all unrelated to the intervention. Skew in the baseline data for the Pelvic Floor Impact Questionnaire-7, the influence of the global COVID-19 pandemic, the potential effects of crossover and the lack of ethnic diversity in the recruited sample were possible limitations. Conclusions: Self-management was acceptable and cost-effective, led to fewer complications and did not improve or worsen quality of life for women with prolapse compared with clinic-based care. Future research is needed to develop a quality-of-life measure that is sensitive to the changes women desire from treatment. Study registration: This study is registered as ISRCTN62510577. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/82/01) and is published in full in Health Technology Assessment; Vol. 28, No. 23. See the NIHR Funding and Awards website for further award information.

Pelvic organ prolapse is a common and distressing condition experienced by large numbers of women. Prolapse is when the organs that are usually in the pelvis drop down into the vagina. Women experience a feeling of something coming down into the vagina, along with bowel, bladder and sexual problems. One possible treatment is a vaginal pessary. The pessary is a device that is inserted into the vagina and holds the pelvic organs back in their usual place. Women who use a vaginal pessary usually come back to clinic every 6 months to have their pessary removed and replaced; this is called clinic-based care. However, it is possible for a woman to look after the pessary herself; this is called self-management. This study compared self-management with clinic-based care. Three hundred and forty women with prolapse took part; 171 received clinic-based care and 169 undertook self-management. Each woman had an equal chance of being in either group. Women in the self-management group received a 30-minute teaching appointment, an information leaflet, a 2-week follow-up telephone call and a telephone number for their local centre. Women in the clinic-based care group returned to clinic as advised by the treating healthcare professional. Self-management was found to be acceptable. Women self-managed their pessary in ways that suited their lifestyle. After 18 months, there was no difference between the groups in women's quality of life. Women in the self-management group experienced fewer pessary complications than women who received clinic-based care. Self-management costs less to deliver than clinic-based care. In summary, self-management did not improve women's quality of life more than clinic-based care, but it did lead to women experiencing fewer complications and cost less to deliver in the NHS. The findings support self-management as a treatment pathway for women using a pessary for prolapse.

Clinical effectiveness of vaginal pessary self-management vs clinic-based care for pelvic organ prolapse (TOPSY): a randomised controlled superiority trial.

Background: Prolapse affects 30-40% of women. Those using a pessary for prolapse usually receive care as an outpatient. This trial determined effectiveness and cost-effectiveness of pessary self-management (SM) vs clinic-based care (CBC) in relation to condition-specific quality of life (QoL). Methods: Parallel-group, superiority randomised controlled trial, recruiting from 16 May 2018 to 7 February 2020, with follow-up to 17 September 2021. Women attending pessary clinics, ≥18 years, using a pessary (except Shelf, Gellhorn or Cube), with pessary retained ≥2 weeks were eligible. Limited manual dexterity; cognitive deficit; pregnancy; or requirement for non-English teaching were exclusions. SM group received a 30-min teaching session; information leaflet; 2-week follow-up call; and telephone support. CBC group received usual routine appointments. The primary clinical outcome was pelvic floor-specific QoL (PFIQ-7), and incremental net monetary benefit for cost-effectiveness, 18 months post-randomisation. Group allocation was by remote web-based application, minimised on age, user type (new/existing) and centre. Participants, intervention deliverers, researchers and the statistician were not blinded. The primary analysis was intention-to-treat based. Trial registration: https://doi.org/10.1186/ISRCTN62510577. Findings: The requisite 340 women were randomised (169 SM, 171 CBC) across 21 centres. There was not a statistically significant difference between groups in PFIQ-7 at 18 months (mean SM 32.3 vs CBC 32.5, adjusted mean difference SM-CBC -0.03, 95% CI -9.32 to 9.25). SM was less costly than CBC. The incremental net benefit of SM was £564 (SE £581, 95% CI -£576 to £1704). A lower percentage of pessary complications was reported in the SM group (mean SM 16.7% vs CBC 22.0%, adjusted mean difference -3.83%, 95% CI -6.86% to -0.81%). There was no meaningful difference in general self-efficacy. Self-managing women were more confident in self-management activities. There were no reported suspected unexpected serious adverse reactions, and 31 unrelated serious adverse events (17 SM, 14 CBC). Interpretation: Pessary self-management is cost-effective, does not improve or worsen QoL compared to CBC, and has a lower complication rate. Funding: National Institute for Health and Care Research, Health Technology Assessment Programme (16/82/01).

Clinical and cost-effectiveness of vaginal pessary self-management compared to clinic-based care for pelvic organ prolapse: protocol for the TOPSY randomised controlled trial.

BACKGROUND: Pelvic organ prolapse (or prolapse) is a common condition in women where the pelvic organs (bladder, bowel or womb) descend into the vagina and cause distressing symptoms that adversely affect quality of life. Many women will use a vaginal pessary to treat their prolapse symptoms. Clinic-based care usually consists of having a pessary fitted in a primary or secondary care setting, and returning approximately every 6 months for healthcare professional review and pessary change. However, it is possible that women could remove, clean and re-insert their pessary themselves; this is called self-management. This trial aims to assess if self-management of a vaginal pessary is associated with better quality of life for women with prolapse when compared to clinic-based care. METHODS: This is a multicentre randomised controlled trial in at least 17 UK centres. The intervention group will receive pessary self-management teaching, a self-management information leaflet, a follow-up phone call and access to a local telephone number for clinical support. The control group will receive the clinic-based pessary care which is standard at their centre. Demographic and medical history data will be collected from both groups at baseline. The primary outcome is condition-specific quality of life at 18 months' post-randomisation. Several secondary outcomes will also be assessed using participant-completed questionnaires. Questionnaires will be administered at baseline, 6, 12 and 18 months' post-randomisation. An economic evaluation will be carried out alongside the trial to evaluate cost-effectiveness. A process evaluation will run parallel to the trial, the protocol for which is reported in a companion paper. DISCUSSION: The results of the trial will provide robust evidence of the effectiveness of pessary self-management compared to clinic-based care in terms of improving women's quality of life, and of its cost-effectiveness. TRIAL REGISTRATION: ISRCTN Registry ISRCTN62510577 . Registered on June 10, 2017.

Surgical interventions for uterine prolapse and for vault prolapse: the two VUE RCTs.

BACKGROUND: New surgical approaches for apical prolapse have gradually been introduced, with few prospective randomised controlled trial data to evaluate their safety and efficacy compared with traditional methods. OBJECTIVE: To compare surgical uterine preservation with vaginal hysterectomy in women with uterine prolapse and abdominal procedures with vaginal procedures in women with vault prolapse in terms of clinical effectiveness, adverse events, quality of life and cost-effectiveness. DESIGN: Two parallel randomised controlled trials (i.e. Uterine and Vault). Allocation was by remote web-based randomisation (1 : 1 ratio), minimised on the need for concomitant anterior and/or posterior procedure, concomitant incontinence procedure, age and surgeon. SETTING: UK hospitals. PARTICIPANTS: Uterine trial - 563 out of 565 randomised women had uterine prolapse surgery. Vault trial - 208 out of 209 randomised women had vault prolapse surgery. INTERVENTIONS: Uterine trial - uterine preservation or vaginal hysterectomy. Vault trial - abdominal or vaginal vault suspension. MAIN OUTCOME MEASURES: The primary outcome measures were women's prolapse symptoms (as measured using the Pelvic Organ Prolapse Symptom Score), prolapse-specific quality of life and cost-effectiveness (as assessed by incremental cost per quality-adjusted life-year). RESULTS: Uterine trial - adjusting for baseline and minimisation covariates, the mean Pelvic Organ Prolapse Symptom Score at 12 months for uterine preservation was 4.2 (standard deviation 4.9) versus vaginal hysterectomy with a Pelvic Organ Prolapse Symptom Score of 4.2 (standard deviation 5.3) (mean difference -0.05, 95% confidence interval -0.91 to 0.81). Serious adverse event rates were similar between the groups (uterine preservation 5.4% vs. vaginal hysterectomy 5.9%; risk ratio 0.82, 95% confidence interval 0.38 to 1.75). There was no difference in overall prolapse stage. Significantly more women would recommend vaginal hysterectomy to a friend (odds ratio 0.39, 95% confidence interval 0.18 to 0.83). Uterine preservation was £235 (95% confidence interval £6 to £464) more expensive than vaginal hysterectomy and generated non-significantly fewer quality-adjusted life-years (mean difference -0.004, 95% confidence interval -0.026 to 0.019). Vault trial - adjusting for baseline and minimisation covariates, the mean Pelvic Organ Prolapse Symptom Score at 12 months for an abdominal procedure was 5.6 (standard deviation 5.4) versus vaginal procedure with a Pelvic Organ Prolapse Symptom Score of 5.9 (standard deviation 5.4) (mean difference -0.61, 95% confidence interval -2.08 to 0.86). The serious adverse event rates were similar between the groups (abdominal 5.9% vs. vaginal 6.0%; risk ratio 0.97, 95% confidence interval 0.27 to 3.44). The objective anterior prolapse stage 2b or more was higher in the vaginal group than in the abdominal group (odds ratio 0.38, 95% confidence interval 0.18 to 0.79). There was no difference in the overall prolapse stage. An abdominal procedure was £570 (95% confidence interval £459 to £682) more expensive than a vaginal procedure and generated non-significantly more quality-adjusted life-years (mean difference 0.004, 95% confidence interval -0.031 to 0.041). CONCLUSIONS: Uterine trial - in terms of efficacy, quality of life or adverse events in the short term, no difference was identified between uterine preservation and vaginal hysterectomy. Vault trial - in terms of efficacy, quality of life or adverse events in the short term, no difference was identified between an abdominal and a vaginal approach. FUTURE WORK: Long-term follow-up for at least 6 years is ongoing to identify recurrence rates, need for further prolapse surgery, adverse events and cost-effectiveness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86784244. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 13. See the National Institute for Health Research Journals Library website for further project information.

About 1 in 10 women has pelvic organ prolapse (POP) surgery, and around three of these women require a further operation. The aim of this study was to identify the most appropriate surgery for two different types of POP found in women: (1) when the uterus itself has come down ­ the Uterine trial ­ and (2) when a previous hysterectomy has resulted in the top of the vagina coming down ­ the Vault trial. In the Uterine trial, preserving the uterus was compared with removing it vaginally. In the Vault trial, uplifting and supporting the vault prolapse using an abdominal approach was compared with a vaginal approach. Women were asked about their prolapse and other symptoms affecting their quality of life (QoL). The majority of women reported that their prolapse symptoms and QoL improved after surgery. The women's prolapse was also measured by clinical examination before and 12 months after their operation. All of these results were compared between the different procedures. It was found that all the surgical procedures were successful within the 12-month review period. Abdominal surgery in the Vault trial as well as any that was required in the Uterine trial, was, however, slightly less cost-effective. Serious complications and the need for further prolapse surgery were similar in all groups. A small number of women did require additional surgery for prolapse recurrence or for small mesh exposure when additional or prolapse procedures had involved mesh. Women in both trials will be followed up for at least 6 years to determine longer-term costs and consequences.

Clinical effectiveness and cost-effectiveness of surgical options for the management of anterior and/or posterior vaginal wall prolapse: two randomised controlled trials within a comprehensive cohort study - results from the PROSPECT Study.

BACKGROUND: The use of mesh in prolapse surgery is controversial, leading to a number of enquiries into its safety and efficacy. OBJECTIVE: To compare synthetic non-absorbable mesh inlay, biological graft and mesh kit with a standard repair in terms of clinical effectiveness, adverse effects, quality of life (QoL), costs and cost-effectiveness. DESIGN: Two randomised controlled trials within a comprehensive cohort (CC) study. Allocation was by a remote web-based randomisation system in a 1 :1 : 1 ratio (Primary trial) or 1 : 1 : 2 ratio (Secondary trial), and was minimised on age, type of prolapse repair planned, need for a concomitant continence procedure, need for a concomitant upper vaginal prolapse procedure and surgeon. Participants and outcome assessors were blinded to randomisation; participants were unblinded if they requested the information. Surgeons were not blinded to allocated procedure. SETTING: Thirty-five UK hospitals. PARTICIPANTS: Primary study: 2474 women in the analysis (including 1348 randomised) having primary anterior or posterior prolapse surgery. Secondary study: 398 in the analysis (including 154 randomised) having repeat anterior or posterior prolapse surgery. CC3: 215 women having either uterine or vault prolapse repair. INTERVENTIONS: Anterior or posterior repair alone, or with mesh inlay, biological graft or mesh kit. MAIN OUTCOME MEASURES: Prolapse symptoms [Pelvic Organ Prolapse Symptom Score (POP-SS)]; prolapse-specific QoL; cost-effectiveness [incremental cost per quality-adjusted life-year (QALY)]. RESULTS: Primary trials: adjusting for baseline and minimisation covariates, mean POP-SS was similar for each comparison {standard 5.4 [standard deviation (SD) 5.5] vs. mesh 5.5 (SD 5.1), mean difference (MD) 0.00, 95% confidence interval (CI) -0.70 to 0.71; standard 5.5 (SD 5.6) vs. graft 5.6 (SD 5.6), MD -0.15, 95% CI -0.93 to 0.63}. Serious non-mesh adverse effects rates were similar between the groups in year 1 [standard 7.2% vs. mesh 7.8%, risk ratio (RR) 1.08, 95% CI 0.68 to 1.72; standard 6.3% vs. graft 9.8%, RR 1.57, 95% CI 0.95 to 2.59]. There were no statistically significant differences between groups in any other outcome measure. The cumulative mesh complication rates over 2 years were 2 of 430 (0.5%) for standard repair (trial 1), 46 of 435 (10.6%) for mesh inlay and 2 of 368 (0.5%) for biological graft. The CC findings were comparable. Incremental costs were £363 (95% CI -£32 to £758) and £565 (95% CI £180 to £950) for mesh and graft vs. standard, respectively. Incremental QALYs were 0.071 (95% CI -0.004 to 0.145) and 0.039 (95% CI -0.041 to 0.120) for mesh and graft vs. standard, respectively. A Markov decision model extrapolating trial results over 5 years showed standard repair had the highest probability of cost-effectiveness, but results were surrounded by considerable uncertainty. Secondary trials: there were no statistically significant differences between the randomised groups in any outcome measure, but the sample size was too small to be conclusive. The cumulative mesh complication rates over 2 years were 7 of 52 (13.5%) for mesh inlay and 4 of 46 (8.7%) for mesh kit, with no mesh exposures for standard repair. CONCLUSIONS: In women who were having primary repairs, there was evidence of no benefit from the use of mesh inlay or biological graft compared with standard repair in terms of efficacy, QoL or adverse effects (other than mesh complications) in the short term. The Secondary trials were too small to provide conclusive results. LIMITATIONS: Women in the Primary trials included some with a previous repair in another compartment. Follow-up is vital to identify any long-term potential benefits and serious adverse effects. FUTURE WORK: Long-term follow-up to at least 6 years after surgery is ongoing to identify recurrence rates, need for further prolapse surgery, adverse effects and cost-effectiveness. TRIAI REGISTRATION: Current Controlled Trials ISRCTN60695184. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 95. See the NIHR Journals Library website for further project information.