Award Title: Long-Term Outcomes Of Synthetic Mid-Urethral Slings (Mesh Tapes) In Surgical Treatment Of Stress Urinary Incontinence In Women – A Long-term Follow-Up Of The SIMS RCT
Funder: Chief Scientist Office, Scotland

Abstract: Urinary incontinence in women is a major issue for the NHS and for society, with the number affected and cost of treatment posing a significant burden on healthcare. _x000D_
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Stress Urinary Incontinence (SUI) is the involuntary loss of urine through exercise, laughing, etc. It is the most common form of incontinence in premenopausal women and can have a significant negative effect on women’s quality of life. Non-surgical treatments seek to increase the support of the urethra with pelvic floor exercises but if these fail then surgery is the only alternative._x000D_
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In the most common surgical procedure, standard mid urethral slings (SMUS or mesh tape), a long strip of polypropylene mesh/ tape is placed under the urethra to provide support. An alternative procedure, single-incision mini-sling (SIMS) is almost 50% less mesh volume and designed to have advantages over SMUS. A pilot study has shown SIMS to have fewer operative complications; less pain during and after the procedure; can be done under local anaesthesia; with earlier recovery of participants; shorter hospital stay; earlier return to normal activities and/or work. Economic analysis has also shown potential economic benefit to the NHS resources and wider society._x000D_
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In the HTA-funded SIMS study 600 women, aged over 18 years, from 21 hospitals in the UK randomly received either a SIMS or SMUS procedure. The progress of these women has been followed up over 3 years, post operatively, measuring potential benefits, risks and costs associated with each procedure and will be reported fully in early 2021.  It will help inform decision making for patients with SUI, their surgeons and the relevant policy makers with regards the most clinically and cost-effective procedure for women with SUI._x000D_
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We now propose to further follow-up these women (SIMS cohort) up-to 10 years following their operation. The aim of the SIMS long-term follow-up (up to 10 years) is three-fold.  Firstly, to provide women, clinicians and policy makers with further clinical and economic information to aid decision making. The embedded qualitative study will explore women’s voices about the decision-making process to undergo SUI surgery.  Secondly, to provide detailed long-term safety information on mesh based SUI surgical procedures.  Thirdly, the duration of this long-term follow-up (10 years) will provide new information on the landscape of any late-onset adverse events and associated surgical procedures._x000D_
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We have consulted with women and the public to decide the optimum length of the long-term follow-up. Our team is the same expert team that delivered the initial SIMS study and further enhanced with two expert clinicians and two patients/ public representatives. We will send yearly questionnaires to the SIMS participants. We will ask about their urinary symptoms and how they affect their quality of life and any treatments they have received since the SIMS study operation. We will use the same follow-up tools and process that we used in the initial SIMS study and have proven successful in keeping the study participants well engaged with the study (87% and 81% response rates at 1 & 3 years respectively). We will collect information on further treatments for continence or adverse events from medical records and routine data sources. We will ask participants to take part in an interview about their experiences of treatment, the impact on their life, and what they think with hind sight about the treatment decisions they made.

Lay Abstract: Research Question: What is the long-term safety, effectiveness and cost effectiveness of synthetic mid-urethral slings (MUS - mesh tapes) in surgical treatment of stress urinary incontinence (SUI)?_x000D_
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Background: Urinary incontinence is a common and disabling condition affecting women of all ages but primarily over 40s. SUI is the most common type of UI and often requires surgery. MUS (mesh-based procedure) have been the mainstay of surgical treatment for SUI for the last 2 decades. In the last 5years, there has been a growing public concern on the lack of robust, industry independent evidence on MUS long-term effectiveness and safety.  The urgent need for this evidence has been highlighted by the recent NICE guideline (NG123), Cochrane review and the 2020 public inquiry report “First Do No Harm”.  _x000D_
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Aim: To determine the long-term safety, effectiveness and cost effectiveness of MUS (mesh) in surgical treatment of SUI in women while comparing single incision mini-slings (SIMS) versus standard mid-urethral slings (SMUS). _x000D_
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Methods: Long-term follow-up of the SIMS trial participants using annual questionnaires up to 10 years follow-up. Primary outcome is patient overall assessment of the outcome of the procedure using PGI-I validated questionnaire (success defined as Very much/Much Improved). The primary economic outcome will be incremental cost per quality adjusted life years (QALY) gained at 10 years. Secondary outcomes include composite outcome of success on PGI-I and no further continence surgery; late onset (>3 years) adverse events (AEs); reoperation rates for SUI and/ or treatment of AEs; impact of the procedure on women’s QoL and sexual function. We will use patients’ medical records to ascertain type of further surgery received / admission for AEs. We will use routinely collected dataset on hospital admissions and procedures (NHS Digital and eDRIS) to enhance the quality of our data including non-responders to follow-up questionnaires. We have also included an embedded qualitative study using semi-structured interviews that will explore: patient experiences/ satisfaction with treatment and impact on QoL and; patient perceptions of decision process and decision outcomes (e.g. decisional regret and decisional conflict). Analysis will use intention to treat but we will also use a secondary per protocol analysis.  _x000D_
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Study Timeline: Start June 2021. Months 1-4 study initiation, Months 1-78 complete annual follow-up up-to 10 years; Months 43-50 the 7-year analysis, write-up and publication, including qualitative component; Months: 75 and 82: routinely collected dataset reports; Months: 79-82: final analysis including health economic analysis, and write-up._x000D_
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Impact and Dissemination: The SIMS long-term results are expected to have a significant impact due to the ongoing highly publicised public debate on the use of mesh in women with SUI worldwide. It will allow us to provide robust long-term data on the use of mesh to treat SUI in women which are currently not available. It will also provide crucial evidence whether the technology of using significantly less mesh volume in SIMS (50% less than SMUS) has comparable longevity and safety compared to standard length MUS. If proven this could change clinical practice towards safer use of mesh procedures. The results of the study will be included in updates of NICE and EAU guidelines, which directly influence practice in the UK and worldwide respectively.

Research Activity Codes: 6.3 MEDICAL DEVICES
Health Categories: RENAL AND UROGENITAL