Title: Female Urgency, Trial of Urodynamics as Routine Evaluation (FUTURE study); a superiority randomised clinical trial to evaluate the effectiveness and cost effectiveness of invasive urodynamic investigations in management of women with refractory overactive bladder symptoms
Funder: Chief Scientist Office, Scotland

Abstract: Background: There is a clear uncertainty on whether invasive Urodynamics investigations improve the treatment outcomes in women with refractory overactive bladder (OAB). Aim: To assess the clinical and cost-effectiveness of routine Urodynamics over and above comprehensive clinical assessment only in women being considered for invasive treatments for refractory OAB. Design & Sample size: A pragmatic superiority RCT. Clinicians and PPI established that a minimum superiority margin of 10% improved patient-reported outcomes is required for the NHS to adopt routine Urodynamics in patients being considered for invasive treatments for refractory OAB. Previous evidence showed patient-reported success rate of ~ 60% following treatments irrespective of Urodynamics diagnosis. So for 90% power and a 5% level of significance, 986 participants are needed, rising to 1096 (or 548/group) to allow for 10% attrition at 15 months post randomisation. An internal pilot phase will establish the feasibility of our recruitment projection with clear stop/go criteria. Eligible participants are women aged >18 years, who are being considered for invasive treatment for refractory OAB. Women would have failed conservative (pelvic floor exercise/ behavioural therapy) and pharmacological treatment (2 different drugs). Women with mixed urinary incontinence will be included if OAB symptoms are the most bothersome Assessment: Participants will undergo a baseline assessment including completion of validated symptom severity and quality of life (QoL) questionnaires; 3-day bladder diary and a bladderscan. Participants will be randomised to undergo either comprehensive clinical assessment only versus comprehensive clinical assessment and Urodynamics. In both study arms, participants will be offered evidence-based treatments for refractory OAB, in line with the NICE guideline and as per the defined treatment pathways. Setting: > 40 secondary and tertiary care hospitals have agreed to participate. We will use a regional hubs structure to enhance recruitment and facilitate study management. Study Duration: 48 months The primary outcome measure is the patient-reported success at 15 months post-randomisation as measured by the Patient Global Impression of Improvement; a robust and validated tool in assessment of treatment outcomes of refractory OAB. The primary economic outcome will be the incremental cost per quality adjusted life year (QALY) gained of Urodynamics compared to comprehensive clinical assessment only - modelled over the lifetime of the patients. The secondary outcomes include improvement in OAB symptoms as assessed by ICIQ-OAB questionnaire; objective reduction of urgency/ urgency incontinence episodes on the bladder diary; health-related QoL profile derived from EQ-5D-5L and ICIQ-LUTSqol; adverse events and further treatments received. We aim to explore the clinical and cost-effectiveness of different sequence of treatments. A robust protocol for standardisation of Urodynamic practice across the collaborating units has been developed according to the ICS Good Urodynamics Practice. A Qualitative study is embedded within the RCT whose main objectives is to explore: 1. Participants’ attitudes to invasive testing and expected outcomes (prior to randomisation or knowing their allocated study group); 2. Participants’ attitudes to potential treatment options (prior to randomisation or knowing their allocated study group); 3. Participants’ experience of Urodynamics and opinions regarding treatment outcome to include evaluation of treatment satisfaction or desire for further treatment (3 to 6 months post treatment; 4. Surgeon attitudes to the influence of Urodynamics on decision making (at start of the study and 6 to12 months after starting recruitment at their sites).

Lay abstract: Overactive bladder (OAB) affects 12-14% of the adult female population in the UK. Symptoms include urgency (being unable to hold-on); Urgency Incontinence (UUI); increased frequency (going to pass urine more frequently); and waking up at night to pass urine. The cause of OAB may be uncontrollable contractions of the bladder called detrusor overactivity. Although rarely life-threatening, OAB can have a considerable negative impact on patients’ quality of life, restricting their social life and ability to work, and up-to social isolation in severe cases. The health-related costs for management of OAB/UUI poses a significant burden and were estimated at approximately €7 billion in 2005 for 6 European countries including the UK OAB is first treated with lifestyle changes (such as reducing caffeine intake); pelvic floor exercises; bladder training and certain medications; these treatments do not work in 25-40% of patients (i.e. refractory OAB). These patients may be offered second line treatments such as injections of BOTOX into the bladder wall or SNM (an implant in the buttock which stimulates the bladder nerves in the lower spine). Before recommending second line treatments, doctors are advised to perform a diagnostic invasive test called Urodynamics to confirm the diagnosis. The test involves passing a thin tube into the bladder and another one into the back passage to measure the bladder activity and episodes of urinary incontinence (UI). Patients often find Urodynamics embarrassing and uncomfortable and some get cystitis after the test. When asked, patients felt the test could be justified if it improves the treatment outcomes. However, in about one third of the patients, Urodynamics may not show the cause of the OAB/UI and patients may not be offered treatments, which could otherwise improve their condition. We propose a study to evaluate Urodynamics in patients with refractory OAB who wish to receive further treatment. Patients who fit the criteria for the study, will be asked to take part at many hospitals in the UK to find out whether or not undergoing Urodynamics improve the subsequent treatment outcomes. We will also look at whether the tests provide value for money for the NHS. Patients who agree to take part will be randomly assigned to undergo Urodynamics or Clinical assessment only. In both groups, women will be offered standard treatments for refractory OAB as per clearly defined treatment pathways which were developed in line with the national guidelines. The outcomes of treatment will be measured approximately 3 and 12 months after treatment. Patients will be asked to fill in questionnaires about their urinary symptoms; quality of life; further treatment received and any adverse events. We will compare the results of treatment for patients who received Urodynamics with those who did not. There are no perceived risks for the patients by participating in the study. Patients will not undergo any invasive tests, for research purposes, within the study. The study team includes experts in Urology & Gynaecology from all corners of the UK, working with an internationally renowned clinical trials unit, statisticians, medical engineer, qualitative researchers and health economists. The Bladder and Bowel Foundation (a large Patient support group) is a joint co-applicant and has participated in the development of the study. The Cystitis & OAB foundation will further advise on patients' perspective.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL