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.

Does variation of surgical technique affect native tissue anterior pelvic organ prolapse repair outcomes?

INTRODUCTION AND HYPOTHESIS: The Variation in Surgical Technique study (VaST), demonstrated the large variation in surgical techniques used in native tissue (NT) anterior pelvic organ prolapse (POP) repairs. However, there are few comparative studies of different surgical techniques. This study was aimed at exploring whether surgical technique influenced the outcomes of NT anterior POP repairs. METHODS: The surgical techniques of 22 consultant surgeons performing NT anterior POP repairs were filmed and categorised. These surgeons performed 809 anterior repairs within the PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trial (PROSPECT). Logistical regression models were used to determine the influence of the different surgical techniques on subjective and objective outcomes, using data collected during PROSPECT. RESULTS: In adjusted multivariate linear regression models, fascial-flap repair was associated with an improved subjective outcome (POP-SS) compared with midline plication (ß = -2.50 [-4.42 to -0.57]; p = 0.01). At 12 months, separate fascial defect repair was associated with a poorer objective outcome than midline plication (OR 6.06 [1.82-3.52], p = 0.006). At 24 months, deep dissection was associated with a poorer POP-SS than superficial dissection (0.32-2.60, p = 0.0). Continuous-locking closure of the skin was also associated with improved POP-SS compared with continuous non-locking closure (12 months: ß = -1.94 [-3.42 to -0.45], p = 0.01). CONCLUSION: Surgical technique may influence the outcome of native tissue anterior POP repairs. Our results should not change practice but inform future research; to develop methods of explicitly recording surgical techniques and allow confirmation of the effect of these aspects of technique on outcome.

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).

PROSPECT: 4- and 6-year follow-up of a randomised trial of surgery for vaginal prolapse.

INTRODUCTION AND HYPOTHESIS: Our aim was to compare the mid-term results of native tissue, biological xenograft and polypropylene mesh surgery for women with vaginal wall prolapse. METHODS: A total of 1348 women undergoing primary transvaginal repair of an anterior and/or posterior prolapse were recruited between January 2010 and August 2013 from 35 UK centres. They were randomised by remote allocation to native tissue surgery, biological xenograft or polypropylene mesh. We performed both 4- and 6-year follow-up using validated patient-reported outcome measures. RESULTS: At 4 and 6 years post-operation, there was no clinically important difference in Pelvic Organ Prolapse Symptom Score for any of the treatments. Using a strict composite outcome to assess functional cure at 6 years, we found no difference in cure among the three types of surgery. Half the women were cured at 6 years but only 10.3 to 12% of women had undergone further surgery for prolapse. However, 8.4% of women in the mesh group had undergone further surgery for mesh complications. There was no difference in the incidence of chronic pain or dyspareunia between groups. CONCLUSIONS: At the mid-term outcome of 6 years, there is no benefit from augmenting primary prolapse repairs with polypropylene mesh inlays or biological xenografts. There was no evidence that polypropylene mesh inlays caused greater pain or dyspareunia than native tissue repairs.

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.

The TOPSY pessary self-management intervention for pelvic organ prolapse: a study protocol for the process evaluation.

BACKGROUND: Process evaluations have become a valued component, alongside clinical trials, of the wider evaluation of complex health interventions. They support understanding of implementation, and fidelity, related to the intervention and provide valuable insights into what is effective in a practical setting by examining the context in which interventions are implemented. The TOPSY study consists of a large multi-centre randomised controlled trial comparing the effectiveness of pessary self-management with clinic-based care in improving women's condition-specific quality of life, and a nested process evaluation. The process evaluation aims to examine and maximise recruitment to the trial, describe intervention fidelity and explore participants' and healthcare professionals' experiences. METHODS: The trial will recruit 330 women from approximately 17 UK centres. The process evaluation uses a mixed-methods approach. Semi-structured interviews will be conducted with randomised women (18 per randomised group/n = 36), women who declined trial participation but agreed to interview (non-randomised women) (n = 20) and healthcare professionals recruiting to the trial (n ~ 17) and delivering self-management and clinic-based care (n ~ 17). The six internal pilot centres will be asked to record two to three recruitment discussions each (total n = 12-18). All participating centres will be asked to record one or two self-management teaching appointments (n = 30) and self-management 2-week follow-up telephone calls (n = 30). Process data (quantitative and qualitative) will be gathered in participant completed trial questionnaires. Interviews will be analysed thematically and recordings using an analytic grid to identify fidelity to the intervention. Quantitative analysis will be predefined within the process evaluation analysis plan. DISCUSSION: The wide variety of pessary care delivered across the UK for women with pelvic organ prolapse presents specific localised contexts in which the TOPSY interventions will be implemented. Understanding this contextual variance is central to understanding how and in what circumstances pessary self-management can be implemented (should it be effective). The inclusion of non-randomised women provides an innovative way of collecting indispensable information about eligible women who decline trial participation, allowing broader contextualisation and considerations of generalisability of trial findings. Methodological insights from examination of recruitment processes and mechanisms have the potential to inform recruitment mechanisms and future recruitment strategies and study designs. TRIAL REGISTRATION: ISRCTN62510577 . Registered on 6 October 2017.

It is unprecedented: trial management during the COVID-19 pandemic and beyond.

The COVID-19 pandemic has presented unique challenges for the clinical trial community, both in the rapid establishment of COVID-19 clinical trials and many existing non-COVID-19 studies either being temporarily paused (whether that is a complete pause or pause in some activities) and/or adapting their processes. Trial managers have played a key role in decision-making, undertaking risk assessments and adapting trial processes, working closely with other members of the research team. This article presents some of the ways in which trial management processes have been altered and the key role that trial managers have played. It has been born out of discussions between trial managers in the UK who are members of the UK Trial Managers' Network (UKTMN), a national network of trial management professionals managing non-commercial trials.In these unprecedented times, clinical trials have faced many uncertainties and broad-ranging challenges encompassing a range of activities including prioritising patient safety amidst the pandemic, consenting and recruiting new participants into trials, data collection and management and intervention delivery. In many cases, recruitment has been paused whilst mitigations have been put in place to continue data collection. Innovative solutions have been implemented to ensure we continue, where possible, to deliver high-quality clinical trials. Technology has provided many solutions to these challenges, and trial managers have adapted to new ways of working whilst continuing to deliver their clinical trials. Trial management groups are now faced with new uncertainties around re-starting clinical trials, and it is unclear currently how this will go, though working together with sponsors, funders and site teams is clearly a priority.Clinical trial teams have worked together to ensure their trials have adapted quickly whilst ensuring participant safety is given utmost importance. There are clear examples where the trial community have come together to share experiences and expertise, and this should continue in the future to ensure the innovative practices developed become embedded in the design and conduct of clinical trials in the future.

How to deal with a temporary suspension and restarting your trial: our experiences and lessons learnt.

Whilst the issues around early termination of randomised controlled trials (RCTs) are well documented in the literature, trials can also be temporarily suspended with the real prospect that they may subsequently restart. There is little guidance in the literature as to how to manage such a temporary suspension. In this paper, we describe the temporary suspension of a trial within our clinical trials unit because of concerns over the safety of transvaginal synthetic mesh implants. We also describe the challenges, considerations, and lessons learnt during the suspension that we are now applying in the current COVID-19 pandemic which has led to activities in many RCTs across the world undergoing a temporary suspension.There were three key phases within the temporary suspension: the decision to suspend, implementation of the suspension, and restarting. Each of these phases presented individual challenges which are discussed within this paper, along with the lessons learnt. There were obvious challenges around recruitment, delivery of the intervention, and follow-up. Additional challenges included communication between stakeholders, evolving risk assessment, updates to trial protocol and associated paperwork, maintaining site engagement, data-analysis, and workload within the trial team and Sponsor organisation.Based on our experience of managing a temporary suspension, we developed an action plan and guidance (see Additional File 1) for managing a significant trial event, such as a temporary suspension. We have used this document to help us manage the suspension of activities within our portfolio of trials during the current COVID-19 pandemic.

Surgery for women with endometrioma prior to in vitro fertilisation: proposal for a feasible multicentre randomised clinical trial in the UK.

STUDY QUESTION: Is it feasible to undertake a randomised controlled trial to establish whether surgical removal of endometrioma or not, improves live birth rates from IVF? SUMMARY ANSWER: A randomised controlled trial (RCT) comparing surgery versus no surgery to endometrioma prior to IVF is only feasible in UK if an adaptive rather than traditional study design is used; this would minimise resource wastage and complete the trial in an acceptable time frame. WHAT IS KNOWN ALREADY: There is wide variation in the management of endometriomas prior to IVF, with decisions about treatment being influenced by personal preferences. STUDY DESIGN SIZE AND DURATION: This was a mixed-methods study consisting of an online survey of clinicians, a focus group and individual interviews with potential trial participants. PARTICIPANTS/MATERIALS SETTING METHODS: Endometriosis and fertility experts across the UK were invited to participate in an online anonymised questionnaire. Potential future trial participants were recruited from a tertiary care fertility centre and invited to participate in either individual interviews or focus groups. MAIN RESULTS AND THE ROLE OF CHANCE: Clinicians and potential trial participants confirmed the need for an RCT to inform the management of an endometrioma prior to IVF. There were 126 clinicians who completed the survey, and the majority (70%) were willing to recruit to a trial. Half of those who responded indicated that they see at least 10 eligible women each year. The main barriers to recruitment were waiting lists for surgery and access to public funding for IVF. One focus group (n = 7) and five interviews were conducted with potential trial participants (n = 3) and their partners (n = 2). The findings from these discussions highlighted that recruitment and retention in a potential RCT could be improved by coordination between IVF and surgical services such that an operation does not delay IVF or affect access to public funding. Live birth was considered the most important outcome with an improvement of at least 10% considered the minimum acceptable by both patients and clinicians. LIMITATIONS REASONS FOR CAUTION: This feasibility study captured views of clinicians across the UK, but as patients were from a single Scottish centre, their views may not be representative of other areas with limited public funding for IVF. WIDER IMPLICATIONS OF THE FINDINGS: There is a need for an appropriately powered RCT to establish whether or not surgical treatment of endometrioma prior to IVF improves live birth rates. There are logistical issues to be considered due to limited number of participants, funding of IVF and waiting times. These could be overcome in a RCT by using an adaptive design which would include a prospectively planned opportunity for modification of specified aspects of the study design based on interim analysis of the data, coordination of IVF treatments and endometriosis surgeries and international collaboration. Similar principles could be used for other questions in fertility where a traditional approach for randomised trials is not feasible. STUDY FUNDING/COMPETING INTERESTS: Funding was received from the NHS Grampian R&D pump priming fund (RG14437-12). S.B. is Editor-in-Chief of HROPEN, and A.W.H. is Deputy Editor of HROPEN. Neither was involved in the review of this manuscript. L.S. reports grants from CSO and NIHR to do endometriosis research, outside the submitted work. K.C. reports grants from NIHR/HTA and CSO during the conduct of the study. J.H.e., A.W.H., J.D., S.B.r., K.B., G.B., J.H.u. and K.G. report no conflict of interest.

Using systematic data categorisation to quantify the types of data collected in clinical trials: the DataCat project.

BACKGROUND: Data collection consumes a large proportion of clinical trial resources. Each data item requires time and effort for collection, processing and quality control procedures. In general, more data equals a heavier burden for trial staff and participants. It is also likely to increase costs. Knowing the types of data being collected, and in what proportion, will be helpful to ensure that limited trial resources and participant goodwill are used wisely. AIM: The aim of this study is to categorise the types of data collected across a broad range of trials and assess what proportion of collected data each category represents. METHODS: We developed a standard operating procedure to categorise data into primary outcome, secondary outcome and 15 other categories. We categorised all variables collected on trial data collection forms from 18, mainly publicly funded, randomised superiority trials, including trials of an investigational medicinal product and complex interventions. Categorisation was done independently in pairs: one person having in-depth knowledge of the trial, the other independent of the trial. Disagreement was resolved through reference to the trial protocol and discussion, with the project team being consulted if necessary. KEY RESULTS: Primary outcome data accounted for 5.0% (median)/11.2% (mean) of all data items collected. Secondary outcomes accounted for 39.9% (median)/42.5% (mean) of all data items. Non-outcome data such as participant identifiers and demographic data represented 32.4% (median)/36.5% (mean) of all data items collected. CONCLUSION: A small proportion of the data collected in our sample of 18 trials was related to the primary outcome. Secondary outcomes accounted for eight times the volume of data as the primary outcome. A substantial amount of data collection is not related to trial outcomes. Trialists should work to make sure that the data they collect are only those essential to support the health and treatment decisions of those whom the trial is designed to inform.

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.

Verifying participant-reported clinical outcomes: challenges and implications.

BACKGROUND: Researchers often rely on trial participants to self-report clinical outcomes (for example, fractures, re-operations). Little information exists as to the 'accuracy' of participant-reported clinical outcomes, particularly in randomised controlled trials (RCTs). To help address this evidence gap, we report four case studies, nested within different RCTs where participant-reported clinical outcome data were compared with those reported by clinicians or extracted from medical notes. METHODS: Four publicly-funded RCTs with different methods of verifying participant-reported outcomes were identified. In KAT, the participants were asked about hospital admissions for any reason. Where it was thought to be relevant to the trial knee, further information was sought from the lead surgeon at the admitting site to confirm whether or not the admission was relevant to the trial knee. In REFLUX, participants were asked about hospital admissions for any reason. For participants who reported a re-operation, further information was sought from the lead surgeon at the admitting site to confirm this. In RECORD, participants were asked three questions regarding broken bones. Where low-trauma fractures were reported, clinical verification was sought, initially from the research nurse at the site. In CATHETER, participants were asked about urinary tract infections (UTIs), and a prescription of antibiotics was provided for the treatment of UTIs following urethral catheterisation. The GPs of those who reported a UTI were contacted to confirm that an antibiotic prescription had been issued for the suspected UTI. RESULTS: In KAT, 397 of 6882 (6%) participant-reported hospital admissions were confirmed as relevant to the trial knee. In REFLUX, 16 of 19 participants (84%) who appeared to have had a re-operation were confirmed as having had one. In RECORD, 473 of 781 (61%) fractures reported by participants were confirmed as being low-trauma fractures. In CATHETER, 429 of 830 participant-reported UTIs (52%) were confirmed as such by the GPs. CONCLUSIONS: We used different approaches in our verification of participant-reported outcomes in clinical trials, and we believe there is no one optimal solution. Consideration of issues such as what information is sought from participants, the phrasing of questions, whether the medical records are a true 'gold standard' and costs and benefits to the RCT may help determine the appropriate approach.

Laparoscopic supracervical hysterectomy compared with second-generation endometrial ablation for heavy menstrual bleeding: the HEALTH RCT.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem that affects many British women. When initial medical treatment is unsuccessful, the National Institute for Health and Care Excellence recommends surgical options such as endometrial ablation (EA) or hysterectomy. Although clinically and economically more effective than EA, total hysterectomy necessitates a longer hospital stay and is associated with slower recovery and a higher risk of complications. Improvements in endoscopic equipment and training have made laparoscopic supracervical hysterectomy (LASH) accessible to most gynaecologists. This operation could preserve the advantages of total hysterectomy and reduce the risk of complications. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of LASH with second-generation EA in women with HMB. DESIGN: A parallel-group, multicentre, randomised controlled trial. Allocation was by remote web-based randomisation (1 : 1 ratio). Surgeons and participants were not blinded to the allocated procedure. SETTING: Thirty-one UK secondary and tertiary hospitals. PARTICIPANTS: Women aged < 50 years with HMB. Exclusion criteria included plans to conceive; endometrial atypia; abnormal cytology; uterine cavity size > 11 cm; any fibroids > 3 cm; contraindications to laparoscopic surgery; previous EA; and inability to give informed consent or complete trial paperwork. INTERVENTIONS: LASH compared with second-generation EA. MAIN OUTCOME MEASURES: Co-primary clinical outcome measures were (1) patient satisfaction and (2) Menorrhagia Multi-Attribute Quality-of-Life Scale (MMAS) score at 15 months post randomisation. The primary economic outcome was incremental cost (NHS perspective) per quality-adjusted life-year (QALY) gained. RESULTS: A total of 330 participants were randomised to each group (total n = 660). Women randomised to LASH were more likely to be satisfied with their treatment than those randomised to EA (97.1% vs. 87.1%) [adjusted difference in proportions 0.10, 95% confidence interval (CI) 0.05 to 0.15; adjusted odds ratio (OR) from ordinal logistic regression (OLR) 2.53, 95% CI 1.83 to 3.48; p < 0.001]. Women randomised to LASH were also more likely to have the best possible MMAS score of 100 (68.7% vs. 54.5%) (adjusted difference in proportions 0.13, 95% CI 0.04 to 0.23; adjusted OR from OLR 1.87, 95% CI 1.31 to 2.67; p = 0.001). Serious adverse event rates were low and similar in both groups (4.5% vs. 3.6%). There was a significant difference in adjusted mean costs between LASH (£2886) and EA (£1282) at 15 months, but no significant difference in QALYs. Based on an extrapolation of expected differences in cost and QALYs out to 10 years, LASH cost an additional £1362 for an average QALY gain of 0.11, equating to an incremental cost-effectiveness ratio of £12,314 per QALY. Probabilities of cost-effectiveness were 53%, 71% and 80% at cost-effectiveness thresholds of £13,000, £20,000 and £30,000 per QALY gained, respectively. LIMITATIONS: Follow-up data beyond 15 months post randomisation are not available to inform cost-effectiveness. CONCLUSION: LASH is superior to EA in terms of clinical effectiveness. EA is less costly in the short term, but expected higher retreatment rates mean that LASH could be considered cost-effective by 10 years post procedure. FUTURE WORK: Retreatment rates, satisfaction and quality-of-life scores at 10-year follow-up will help to inform long-term cost-effectiveness. TRIAI REGISTRATION: Current Controlled Trials ISRCTN49013893. 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. 23, No. 53. See the NIHR Journals Library website for further project information.

Almost 1.5 million women in England and Wales suffer from heavy periods. Initial treatment involves tablets or a medicated coil inserted within the womb. Sometimes these treatments do not work and many women need an operation, either endometrial ablation (EA) (removing the lining of the womb) or a full hysterectomy (complete removal of the womb). Previous studies have shown that a full hysterectomy is better at relieving symptoms, but the risk of complications during surgery is higher and patients take longer to recover fully. A newer operation, laparoscopic (keyhole) supracervical hysterectomy, or 'LASH', removes only the part of the womb that causes periods and preserves the cervix or neck of the womb. Women who have LASH can expect fewer complications, earlier discharge from hospital and quicker recovery time. In this study, we compared EA with LASH by asking women who had either procedure how they felt about it 1 year after their operation. Regardless of which operation they had, most women were very satisfied and felt that their symptoms were better. However, the results were much better for those who had the LASH operation, although these women stayed in hospital for longer and took more time to recover. There was no difference in complications from either surgery, although nearly 1 in 20 women who had an EA returned within 1 year to have their wombs removed in a second operation. Although LASH led to a greater improvement in symptoms and levels of satisfaction, it was more expensive in terms of costs incurred by both the health service and society. Given that some women who had an EA are likely to need a second operation in the future, LASH surgery may provide better value for money in the long term.

Laparoscopic supracervical hysterectomy versus endometrial ablation for women with heavy menstrual bleeding (HEALTH): a parallel-group, open-label, randomised controlled trial.

BACKGROUND: Heavy menstrual bleeding affects 25% of women in the UK, many of whom require surgery to treat it. Hysterectomy is effective but has more complications than endometrial ablation, which is less invasive but ultimately leads to hysterectomy in 20% of women. We compared laparoscopic supracervical hysterectomy with endometrial ablation in women seeking surgical treatment for heavy menstrual bleeding. METHODS: In this parallel-group, multicentre, open-label, randomised controlled trial in 31 hospitals in the UK, women younger than 50 years who were referred to a gynaecologist for surgical treatment of heavy menstrual bleeding and who were eligible for endometrial ablation were randomly allocated (1:1) to either laparoscopic supracervical hysterectomy or second generation endometrial ablation. Women were randomly assigned by either an interactive voice response telephone system or an internet-based application with a minimisation algorithm based on centre and age group (<40 years vs ≥40 years). Laparoscopic supracervical hysterectomy involves laparoscopic (keyhole) surgery to remove the upper part of the uterus (the body) containing the endometrium. Endometrial ablation aims to treat heavy menstrual bleeding by destroying the endometrium, which is responsible for heavy periods. The co-primary clinical outcomes were patient satisfaction and condition-specific quality of life, measured with the menorrhagia multi-attribute quality of life scale (MMAS), assessed at 15 months after randomisation. Our analysis was based on the intention-to-treat principle. The trial was registered with the ISRCTN registry, number ISRCTN49013893. FINDINGS: Between May 21, 2014, and March 28, 2017, we enrolled and randomly assigned 660 women (330 in each group). 616 (93%) of 660 women were operated on within the study period, 588 (95%) of whom received the allocated procedure and 28 (5%) of whom had an alternative surgery. At 15 months after randomisation, more women allocated to laparoscopic supracervical hysterectomy were satisfied with their operation compared with those in the endometrial ablation group (270 [97%] of 278 women vs 244 [87%] of 280 women; adjusted percentage difference 9·8, 95% CI 5·1-14·5; adjusted odds ratio [OR] 2·53, 95% CI 1·83-3·48; p<0·0001). Women randomly assigned to laparoscopic supracervical hysterectomy were also more likely to have the best possible MMAS score of 100 than women assigned to endometrial ablation (180 [69%] of 262 women vs 146 [54%] of 268 women; adjusted percentage difference 13·3, 95% CI 3·8-22·8; adjusted OR 1·87, 95% CI 1·31-2·67; p=0·00058). 14 (5%) of 309 women in the laparoscopic supracervical hysterectomy group and 11 (4%) of 307 women in the endometrial ablation group had at least one serious adverse event (adjusted OR 1·30, 95% CI 0·56-3·02; p=0·54). INTERPRETATION: Laparoscopic supracervical hysterectomy is superior to endometrial ablation in terms of clinical effectiveness and has a similar proportion of complications, but takes longer to perform and is associated with a longer recovery. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

HEALTH: laparoscopic supracervical hysterectomy versus second-generation endometrial ablation for the treatment of heavy menstrual bleeding: study protocol for a randomised controlled trial.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem affecting approximately 1.5 million women in England and Wales with a major impact on their physical, emotional, social and material quality of life. It is the fourth most common reason why women attend gynaecology outpatient clinics and accounts for one-fifth of all gynaecology outpatient referrals. Initial treatment in primary care is medical - either by means of oral or injected medication or the levonorgestrel-intrauterine system (Mirena®). If medical treatment fails then surgical treatment can be offered, either endometrial ablation (EA), which destroys the lining of the cavity of the uterus (endometrium), or hysterectomy, i.e. surgical removal of the uterus. While effective, conventional hysterectomy is invasive and carries a risk of complications due to injury to other pelvic structures. The procedure can be simplified and complications minimised by undertaking a 'supracervical' hysterectomy where the cervix is left in situ and only the body of the uterus removed. Recent advances in endoscopic technologies have facilitated increased use of laparoscopic supracervical hysterectomy (LASH) which can be performed as a day-case procedure and is relatively easy for the surgeon to learn. HEALTH (Hysterectomy or Endometrial AbLation Trial for Heavy menstrual bleeding) aims to address the question 'Is LASH superior to second generation EA for the treatment of HMB in terms of clinical and cost effectiveness?' METHODS/DESIGN: Women aged < 50 years, with HMB, in whom medical treatment has failed and who are eligible for EA will be considered for trial entry. We aim to recruit women from approximately 30 active secondary care centres in the UK NHS who carry out both surgical procedures. All women who consent will complete a diary of pain symptoms from day 1 to day 14 after surgery, postal questionnaires at six weeks and six months after surgery and 15 months post randomisation. Healthcare utilisation questions will also be completed at the six-week, six-month and 15-month time-points. DISCUSSION: Measuring the comparative effectiveness of LASH vs EA will provide the robust evidence required to determine whether the new technique should be adopted widely in the NHS. TRIAL REGISTRATION: International Standard Randomised Controlled Trials, ISRCTN49013893 . Registered on 28 January 2014.

A UK questionnaire survey of current techniques used to perform pelvic organ prolapse repair.

INTRODUCTION AND HYPOTHESIS: Evidence-based medicine should result in better standardisation of practice. This study aims to evaluate whether there remains variation in surgical techniques in native tissue and graft/mesh repairs of pelvic organ prolapse (POP) in UK practice. METHODS: A questionnaire survey was conducted to describe current surgical techniques for native tissue and graft/mesh POP repairs performed by a cohort of UK surgeons recruiting to a large multicentre prolapse trial (PROSPECT). RESULTS: The questionnaire return rate was 90% (n = 56 out of 62). Substantial variations in surgical techniques were seen at every step of the procedure. Native tissue repair: most surgeons used infiltration, 95% (n = 53 out of 56), but the volume used varied (10-80 ml). All but one surgeon performed a midline incision; this surgeon performed an elliptical incision. The depth of tissue dissection varied, being both above and below the vaginal muscularis (fascia). Fascial repair methods included midline, closure of separate fascial defects, paravaginal repair and rectal/levator plication. Graft/mesh repairs: many different products and manufacturers were used. There was variation in the method of attachment of graft/mesh inserts and their placement in relation to the fascia. For both native tissue and graft/mesh repairs, the method of fascial dissection, suturing methods and suture material varied. Most surgeons inserted a pack, 91% (n = 50 out of 55), soaked in varying substances before use. CONCLUSIONS: There is considerable variation between UK-based surgeons in the surgical techniques used to perform both native tissue and graft/mesh-augmented POP repairs. Further research is required to determine whether these differences influence outcome.

Mesh, graft, or standard repair for women having primary transvaginal anterior or posterior compartment prolapse surgery: two parallel-group, multicentre, randomised, controlled trials (PROSPECT).

BACKGROUND: The use of transvaginal mesh and biological graft material in prolapse surgery is controversial and has led to a number of enquiries into their safety and efficacy. Existing trials of these augmentations are individually too small to be conclusive. We aimed to compare the outcomes of prolapse repair involving either synthetic mesh inlays or biological grafts against standard repair in women. METHODS: We did two pragmatic, parallel-group, multicentre, randomised controlled trials for our study (PROSPECT [PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trials]) in 35 centres (a mix of secondary and tertiary referral hospitals) in the UK. We recruited women undergoing primary transvaginal anterior or posterior compartment prolapse surgery by 65 gynaecological surgeons in these centres. We randomly assigned participants by a remote web-based randomisation system to one of the two trials: comparing standard (native tissue) repair alone with standard repair augmented with either synthetic mesh (the mesh trial) or biological graft (the graft trial). We assigned women (1:1:1 or 1:1) within three strata: assigned to one of the three treatment options, comparison of standard repair with mesh, and comparison of standard repair with graft. Participants, ward staff, and outcome assessors were masked to randomisation where possible; masking was obviously not possible for the surgeon. Follow-up was for 2 years after the surgery; the primary outcomes, measured at 1 year and 2 years, were participant-reported prolapse symptoms (i.e. the Pelvic Organ Prolapse Symptom Score [POP-SS]) and condition-specific (ie, prolapse-related) quality-of-life scores, analysed in the modified intention-to-treat population. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN60695184. FINDINGS: Between Jan 8, 2010, and Aug 30, 2013, we randomly allocated 1352 women to treatment, of whom 1348 were included in the analysis. 865 women were included in the mesh trial (430 to standard repair alone, 435 to mesh augmentation) and 735 were included in the graft trial (367 to standard repair alone, 368 to graft augmentation). Because the analyses were carried out separately for each trial (mesh trial and graft trial) some women in the standard repair arm assigned to all treatment options were included in the standard repair group of both trials. 23 of these women did not receive any surgery (15 in the mesh trial, 13 in the graft trial; five were included in both trials) and were included in the baseline analyses only. Mean POP-SS at 1 year did not differ substantially between comparisons (standard 5·4 [SD 5·5] vs mesh 5·5 [5·1], mean difference 0·00, 95% CI -0·70 to 0·71; p=0·99; standard 5·5 [SD 5·6] vs graft 5·6 [5·6]; mean difference -0·15, -0·93 to 0·63; p=0·71). Mean prolapse-related quality-of-life scores also did not differ between groups at 1 year (standard 2·0 [SD 2·7] vs mesh 2·2 [2·7], mean difference 0·13, 95% CI -0·25 to 0·51; p=0·50; standard 2·2 [SD 2·8] vs graft 2·4 [2·9]; mean difference 0·13, -0·30 to 0·56; p=0·54). Mean POP-SS at 2 years were: standard 4·9 (SD 5·1) versus mesh 5·3 (5·1), mean difference 0·32, 95% CI -0·39 to 1·03; p=0·37; standard 4·9 (SD 5·1) versus graft 5·5 (5·7); mean difference 0·32, -0·48 to 1·12; p=0·43. Prolapse-related quality-of-life scores at 2 years were: standard 1·9 (SD 2·5) versus mesh 2·2 (2·6), mean difference 0·15, 95% CI -0·23 to 0·54; p=0·44; standard 2·0 (2·5) versus graft 2·2 (2·8); mean difference 0·10, -0·33 to 0·52; p=0·66. Serious adverse events such as infection, urinary retention, or dyspareunia or other pain, excluding mesh complications, occurred with similar frequency in the groups over 1 year (mesh trial: 31/430 [7%] with standard repair vs 34/435 [8%] with mesh, risk ratio [RR] 1·08, 95% CI 0·68 to 1·72; p=0·73; graft trial: 23/367 [6%] with standard repair vs 36/368 [10%] with graft, RR 1·57, 0·95 to 2·59; p=0·08). The cumulative number of women with a mesh complication over 2 years in women actually exposed to synthetic mesh was 51 (12%) of 434. INTERPRETATION: Augmentation of a vaginal repair with mesh or graft material did not improve women's outcomes in terms of effectiveness, quality of life, adverse effects, or any other outcome in the short term, but more than one in ten women had a mesh complication. Therefore, follow-up is vital to identify any longer-term potential benefits and serious adverse effects of mesh or graft reinforcement in vaginal prolapse surgery. FUNDING: UK National Institute of Health Research.

Two parallel, pragmatic, UK multicentre, randomised controlled trials comparing surgical options for upper compartment (vault or uterine) pelvic organ prolapse (the VUE Study): study protocol for a randomised controlled trial.

BACKGROUND: One in three women who have a prolapse operation will go on to have another operation, though not necessarily in the same compartment. Surgery can result in greater impairment of quality of life than the original prolapse itself (such as the development of new-onset urinary incontinence, or prolapse at a different site). Anterior and posterior prolapse surgery is most common (90 % of operations), but around 43 % of women also have a uterine (34 %) or vault (9 %) procedure at the same time. There is not enough evidence from randomised controlled trials (RCTs) to guide management of vault or uterine prolapse. The Vault or Uterine prolapse surgery Evaluation (VUE) study aims to assess the surgical management of upper compartment pelvic organ prolapse (POP) in terms of clinical effectiveness, cost-effectiveness and adverse events. METHODS/DESIGN: VUE is two parallel, pragmatic, UK multicentre, RCTs (Uterine Trial and Vault Trial). Eligible for inclusion are women with vault or uterine prolapse: requiring a surgical procedure, suitable for randomisation and willing to be randomised. Randomisation will be computer-allocated separately for each trial, minimised on: requiring concomitant anterior and/or posterior POP surgery or not, concomitant incontinence surgery or not, age (under 60 years or 60 years and older) and surgeon. Participants will be randomly assigned, with equal probability to intervention or control arms in either the Uterine Trial or the Vault Trial. Uterine Trial participants will receive either a vaginal hysterectomy or a uterine preservation procedure. Vault Trial participants will receive either a vaginal sacrospinous fixation or an abdominal sacrocolpopexy. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomisation) and also reviewed in clinic 12 months post surgery. The primary outcome is the participant-reported Pelvic Organ Prolapse Symptom Score (POP-SS) at 12 months post randomisation. DISCUSSION: Demonstrating the efficacy of vault and uterine prolapse surgeries is relevant not only to patients and clinicians but also to health care providers, both in the UK and globally. TRIAL REGISTRATION: Current controlled trials ISRCTN86784244 (assigned 19 October 2012), and the first subject was randomly assigned on 1 May 2013.

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.