title: 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.
abstract: The use of mesh in prolapse surgery is controversial, leading to a number of enquiries into its safety and efficacy.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Thirty-five UK hospitals.
  
  
  
  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.
  
  
  
  Anterior or posterior repair alone, or with mesh inlay, biological graft or mesh kit.
  
  
  
  Prolapse symptoms [Pelvic Organ Prolapse Symptom Score (POP-SS)]; prolapse-specific QoL; cost-effectiveness [incremental cost per quality-adjusted life-year (QALY)].
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Current Controlled Trials ISRCTN60695184.
  
  
  
  This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 95. See the NIHR Journals Library website for further project information.
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Glazener
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Breeman
authors.affiliation: Nursing, Midwifery and Allied Health Professionals Research Unit, Glasgow Caledonian University, Glasgow, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Elders
authors.affiliation: Aberdeen Royal Infirmary, Aberdeen, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Hemming
authors.affiliation: Aberdeen Royal Infirmary, Aberdeen, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cooper
authors.affiliation: Derriford Hospital, Plymouth, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Freeman
authors.affiliation: St Mary's Hospital, Manchester, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Smith
authors.affiliation: Nursing, Midwifery and Allied Health Professionals Research Unit, Glasgow Caledonian University, Glasgow, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hagen
authors.affiliation: Patient representative, Aberdeen, UK.
authors.forename: Isobel
authors.initials: I
authors.lastname: Montgomery
authors.affiliation: Health Economics Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Kilonzo
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.|Health Economics Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Dwayne
authors.initials: D
authors.lastname: Boyers
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: McDonald
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Gladys
authors.initials: G
authors.lastname: McPherson
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: MacLennan
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: John
authors.initials: J
authors.lastname: Norrie
mesh_terms: D000328:Adult; D000368:Aged; D003362:Cost-Benefit Analysis; D005260:Female; D013509:Gynecologic Surgical Procedures / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D011183:Postoperative Complications; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D013526:Surgical Mesh; D013536:Suture Techniques; D016896:Treatment Outcome; D014596:Uterine Prolapse / Q000601:surgery*