Title: Vault or Uterine prolapse surgery Evaluation – two parallel randomised controlled trials of surgical options for upper compartment (uterine or vault) pelvic organ prolapse (VUE)
Funder: Chief Scientist Office, Scotland

Abstract: Design: Two parallel randomised controlled trials (RCTs) of surgery for the treatment of women with upper compartment (uterine or vault) pelvic organ prolapse. Minimisation by key prognostic variables (type of prolapse, concomitant operation for incontinence or not, concomitant anterior and/or posterior prolapse operation or none, age and surgeon) will be included. Setting: Forty gynaecological surgery centres in UK hospitals. Target population: Women having upper compartment (uterine or vault) pelvic organ prolapse surgery. Health Technologies being assessed: (A) in women having uterine prolapse surgery: removal of the uterus versus uterine preservation; and (B) in women having vault prolapse surgery: vaginal vault suspension versus abdominal vault suspension. Measurement of costs and outcomes: Outcomes in both groups will be assessed by patient-completed questionnaires (using the Pelvic Organ Prolapse Symptom Score, POP-SS(1)) and clinician-observation of prolapse stage and type (using the POP-Q system (2)) at baseline (before surgery), and at 12 months after surgery, including identification of new prolapse types. Women will also complete a questionnaire at 6 months after surgery. Surgical procedures and complications will be recorded during the hospital stay using standard questionnaires. We will conform to the International Continence Society's recommendations for terminology and standard techniques for measuring outcomes. Consent will be sought for long term follow up but this will be funded separately. An economic evaluation will be an integral component of the study. The point of view adopted will be that of the NHS and the patient. Resource-use data collected will include the costs of the intervention and the use of other primary and secondary NHS services. Both health service costs and non-health service costs will be included, the latter collected from participants. Incremental cost-utility ratios will be computed comparing the interventions for each randomised comparison. The difference in utility will be expressed in terms of Quality Adjusted Life Years (QALYs) estimated from the responses to the EQ-5D. Using the best available data from the literature including the updated Cochrane review, an economic model will be developed that will extrapolate the findings of the study over a longer time horizon. This model will be developed in line with guidelines for best practice. Both the within trial and modelling economic evaluation will involve a deterministic and probabilistic sensitivity analysis to explore the impact of plausible sources of uncertainty. (1) Hagen S et al. Psychometric properties of the pelvic organ prolapse symptom score. BJOG: 2009; 116(1):25-31 (2) Bump RC et al. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. AMJOG: 1996; 175(1):10-17

Lay abstract: Around 1 in 10 women will need prolapse surgery at some point in their lives. Prolapse occurs when the pelvic organs (such as the bladder, the bowel or the womb) come down into, or out of, the vagina. This is caused either by weakness of the connective tissues which normally support these organs or by weak pelvic floor muscles. It is most common in women who have had children, although there has been surprisingly little research into its causes and treatment. There are many different operations for prolapse, depending on the type of prolapse, whether the woman has more than one type and the preference of the gynaecological surgeon. There is a high failure rate after surgery for womb (uterine) prolapse: a quarter of women who have a hysterectomy (removal of the womb) will need a further repair to the vault (top of the vagina) later. This study will address both uterine and vault prolapse. Some women may need an extra procedure if the front or back vaginal walls are also coming down or for leaking urine (incontinence). If necessary, these extra procedures can be carried out at the same time. There is not enough evidence from research to identify which operation is best. Traditionally a uterine prolapse is treated by removal of the womb via the vagina, and a vault prolapse by attaching the top of the vagina to other pelvic ligaments. Some gynaecologists feel that it would be possible to preserve the uterus by attaching it to other pelvic structures with mesh, and that the vault might be better supported by an operation through the abdomen, also using mesh. However, there is no good evidence to support either of these approaches. In particular, a recent review by NICE (the National Institute for Clinical Excellence) has found that there is insufficient information on the efficacy and safety of mesh used in either of these ways. The study will be carried out in at least 40 hospitals in the UK. We will randomise women having surgery to one of two trials: (A) In women having uterine prolapse surgery, the effects of removal of the uterus versus uterine preservation (B) In women having vault prolapse surgery, the effects of a vaginal vault suspension versus an abdominal vault suspension It is likely that there will be mixed costs and benefits for these operations. For example there may be better cure rates with some operations although with a higher chance of complications, or at a higher cost to the NHS or women. Women having surgery for uterine or vault prolapse will be eligible for our trial. They will be given information about the study before they are admitted to hospital. After discussion with their gynaecologist, women will be able to choose whether or not they are willing to be randomised to one of the specified operations. They will sign a consent form approved by the Ethics Committee. Women will have a routine physical examination before surgery and they will complete questionnaires both before and after their operation. Further symptom questionnaires will also be filled in at 6 and 12 months later. The women will be examined and reviewed in outpatients at 12 months after surgery. Our main interest is in the cure or improvement of prolapse symptoms, as reported by the women themselves. We have used these questionnaires and examination methods in a related prolapse surgery trial (PROSPECT) to show that we will be able to measure differences. Ethical approval will be sought for this study. We consider that it is ethical to study this problem using randomisation as this is the gold-standard method most likely to provide an unbiased answer. The procedures used in the study will be standardised and agreed with a team of experienced gynaecologists from the British Society of Urogynaecology. The study team consists of professional health service researchers from across the UK with a wide range of skills and extensive experience in carrying out large multicentre randomised clinical trials, working in collaboration with NHS consultant gynaecologists. All gynaecologists involved in this study will be experienced in each type of surgery to which their patients may be randomised. We have carried out several research studies in women with prolapse, related to how to measure outcomes and how to evaluate different treatments for women with pelvic organ prolapse. We have identified a consumer representative to ensure that women's views are incorporated into the design from the start. She is a grant applicant and has already contributed to the trial design and the participant information sheet of PROSPECT. The costs of the study reflect the large numbers of women and gynaecologists needed to answer the question reliably. Each centre will need a Recruitment Officer to explain the study to the women, to make sure that they understand what they are consenting to, and what they will be expected to do. The study is co-ordinated by a team of specialist health service researchers based at our clinical trials unit, the Centre for Healthcare Randomised Trials in the Health Services Research Unit, University of Aberdeen. The specialists include experts in trial design, statistics, economics, information technology and trial administration. Other costs include: the questionnaires and postage; the follow-up appointments to find out about the women’s health after their operation; and the extra costs to NHS staff for carrying out this research. Within the next 10 years, an extra 1.4 million women will reach the age when they are most likely to need prolapse surgery. This study will show which prolapse operations are the safest and most effective for women with uterine or vault prolapse.

Research activity codes: 6.4 SURGERY
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH