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

Cathryn Glazener, Suzanne Breeman, Andrew Elders, Christine Hemming, Kevin Cooper, Robert Freeman, Anthony R. B. Smith, Suzanne Hagen, Isobel Montgomery, Mary Kilonzo, Dwayne Boyers, Alison McDonald, Gladys McPherson, Graeme MacLennan, John Norrie

Research output: Book/ReportCommissioned report

Abstract

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 (POSS)]; 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.
Original languageEnglish
PublisherNIHR Journals Library
Commissioning bodyNational Institute for Health Research
Number of pages496
DOIs
Publication statusPublished - Jan 2017

Publication series

NameHealth Technology Assessment
PublisherNIHR Journals Library
No.95
Volume20
ISSN (Electronic)1366-5278

Fingerprint

Uterine Prolapse
Cost-Benefit Analysis
Prolapse
Cohort Studies
Randomized Controlled Trials
Inlays
Confidence Intervals
Transplants
Biomedical Technology Assessment
Quality-Adjusted Life Years
Quality of Life
National Institutes of Health (U.S.)
Outcome Assessment (Health Care)
Random Allocation
Costs and Cost Analysis
Odds Ratio
Pelvic Organ Prolapse
Research
Sample Size
Libraries

Keywords

  • vaginal wall prolapse
  • surgical options
  • clinical trials
  • PROSPECT
  • cost-effectiveness

Cite this

Glazener, Cathryn ; Breeman, Suzanne ; Elders, Andrew ; Hemming, Christine ; Cooper, Kevin ; Freeman, Robert ; Smith, Anthony R. B. ; Hagen, Suzanne ; Montgomery, Isobel ; Kilonzo, Mary ; Boyers, Dwayne ; McDonald, Alison ; McPherson, Gladys ; MacLennan, Graeme ; Norrie, John. / 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. NIHR Journals Library, 2017. 496 p. (Health Technology Assessment; 95).
@book{82b565b5b5c14f3f9be251f39c328fa0,
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 = "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 (POSS)]; 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.LimitationsWomen 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.",
keywords = "vaginal wall prolapse, surgical options, clinical trials, PROSPECT , cost-effectiveness",
author = "Cathryn Glazener and Suzanne Breeman and Andrew Elders and Christine Hemming and Kevin Cooper and Robert Freeman and Smith, {Anthony R. B.} and Suzanne Hagen and Isobel Montgomery and Mary Kilonzo and Dwayne Boyers and Alison McDonald and Gladys McPherson and Graeme MacLennan and John Norrie",
note = "According to Romeo, publisher version can be used - ET",
year = "2017",
month = "1",
doi = "10.3310/hta20950",
language = "English",
series = "Health Technology Assessment",
publisher = "NIHR Journals Library",
number = "95",

}

Glazener, C, Breeman, S, Elders, A, Hemming, C, Cooper, K, Freeman, R, Smith, ARB, Hagen, S, Montgomery, I, Kilonzo, M, Boyers, D, McDonald, A, McPherson, G, MacLennan, G & Norrie, J 2017, 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. Health Technology Assessment, no. 95, vol. 20, NIHR Journals Library. https://doi.org/10.3310/hta20950

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. / Glazener, Cathryn; Breeman, Suzanne; Elders, Andrew; Hemming, Christine; Cooper, Kevin; Freeman, Robert; Smith, Anthony R. B.; Hagen, Suzanne; Montgomery, Isobel; Kilonzo, Mary; Boyers, Dwayne; McDonald, Alison; McPherson, Gladys; MacLennan, Graeme; Norrie, John.

NIHR Journals Library, 2017. 496 p. (Health Technology Assessment; Vol. 20, No. 95).

Research output: Book/ReportCommissioned report

TY - BOOK

T1 - 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

AU - Glazener, Cathryn

AU - Breeman, Suzanne

AU - Elders, Andrew

AU - Hemming, Christine

AU - Cooper, Kevin

AU - Freeman, Robert

AU - Smith, Anthony R. B.

AU - Hagen, Suzanne

AU - Montgomery, Isobel

AU - Kilonzo, Mary

AU - Boyers, Dwayne

AU - McDonald, Alison

AU - McPherson, Gladys

AU - MacLennan, Graeme

AU - Norrie, John

N1 - According to Romeo, publisher version can be used - ET

PY - 2017/1

Y1 - 2017/1

N2 - 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 (POSS)]; 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.LimitationsWomen 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.

AB - 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 (POSS)]; 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.LimitationsWomen 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.

KW - vaginal wall prolapse

KW - surgical options

KW - clinical trials

KW - PROSPECT

KW - cost-effectiveness

U2 - 10.3310/hta20950

DO - 10.3310/hta20950

M3 - Commissioned report

T3 - Health Technology Assessment

BT - 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

PB - NIHR Journals Library

ER -