A Prospective, Non-Randomized, Parallel Cohort, Multi-Center Study of Xenform vs. Native Tissue for the Treatment of Women With Anterior/Apical Pelvic Organ Prolapse
Phase: NA
Conditions: Pelvic Organ Prolapse
Sponsor: Boston Scientific Corporation

 
Form/Template 90702637 Rev/Ver AH 
Protocol U9920 – Xenform, 90890750, Rev/Ver AE 
Page 1 of 62 
 
 
 
 
 
PS120081 
Xenform Postmarket Surveillance Study 
 
 
 
CLINICAL PROTOCOL 
 
U9920 
A Prospective, Non-Randomized, Parallel Cohort, Multi-Center Study of Xenform vs. Native 
Tissue for the Treatment of Women with Anterior/Apical Pelvic Organ 
 
 
Sponsored By 
Boston Scientific Corporation 
 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
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PS120081  
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Confidential  
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Contact Information 
Role 
Contact  
Clinical Contact 
Laura Olson 
Clinical Project Manager 
Boston Scientific Corporation – Urology and Pelvic Health Division 
10700 Bren Road West 
Minnetonka, MN 55343 
Tel: 952-930-6428 
Laura.Olson2@bsci.com 
Coordinating  
Principal Investigator 
Peter L. Rosenblatt, MD 
Director of Urogynecology 
Mount Auburn Hospital 
Cambridge, MA  
Tel: 617-354-5452 
plrosen@comcast.net 
 
Original Release: 28 June 2012 
Current Version: 20 March 2018 
Revision History 
Revision 
Number 
Release  
Date 
Template 
Number and 
Version 
Section 
Change 
Reason for Change 
01 
28 September 
2012* 
90702637 
Rev/Ver AC 
Various 
Updates, clarifications 
and responses 
Responses to FDA 
letter dated August 31, 
2012 
02 
15 November 
2012* 
90702637 
Rev/Ver AC 
Various 
Updates, clarifications 
and responses 
Response to FDA 
letter dated October 
18, 2012 
03 
08 March 
2013* 
90702637 
Rev/Ver AC 
Various 
Updates, clarifications 
and responses 
Response to FDA 
letter dated October 
18, 2012 
04 
24 July 
2013* 
90702637 
Rev/Ver AC 
Various 
Updates, clarifications 
and responses 
Response to FDA 
letter dated February 
8, 2013 
05/AA 
20 September 
2013 
90702637 
Rev/Ver AC 
11. Statistical 
Considerations 
Clarification 
Response to FDA 
interactive review 
06/AB 
07 November 
2014 
90702637 
Rev/Ver AD 
7. Design 
Clarified Anterior 
Colporrhaphy 
Language 
To align with standard 
of care 
8. Subject Selection 
Updated Inclusion 
Criteria #3 
To clarify further 
7. Design 
Updated number of 
study site 
To allow for a larger 
number of 
participating sites 
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Revision History 
Revision 
Number 
Release  
Date 
Template 
Number and 
Version 
Section 
Change 
Reason for Change 
8. Subject Selection 
Removed English-
speaking requirement 
To allow enrollment of 
non-English speaking 
subjects 
9. Subject 
Accountability 
Updated Study 
Timeline 
To align with current 
enrollment cadence 
11. Statistical 
Considerations 
Updated Intent-to-
Treat definition 
To clarify definition 
20. Safety Reporting 
Updated Safety 
Reporting 
To align with data 
collection in the 
AUGS PFD Registry 
07/AC 
25 September 
2017* 
90702637 
Rev/Ver AH 
Title Page 
Revised sponsor 
To reflect BSC as 
sponsor 
Contact Information 
Updated Clinical 
Contact 
To reflect current BSC 
Clinical Project 
Manager 
Entire document 
Changed reference to 
the “sponsor” to 
Boston Scientific 
To clarify who the 
sponsor is  
2. Protocol Synopsis-
Study Duration;  
8.1. Scale and Duration;  
11.4.7. Months 6, 12, 
18, 24, 36 Visits 
Deleted “per protocol” 
from subject 
description 
To clarify the study 
population 
2. Protocol Synopsis-
Planned Number of 
Subjects;  
8.1. Scale and Duration 
Deleted reference to 
Xenform subjects 
To clarify which 
subjects will be shared 
from the PFD Registry 
10.1. Point of 
Enrollment 
Revised study 
population description 
To clarify the Intent-
to-Treat and Per 
Protocol groups 
10.1. Point of 
Enrollment 
Revised study timeline 
table 
To update actual and 
expected dates for 
study milestones 
10.2. Withdrawal 
Added sections on 
voluntary and 
involuntary 
withdrawal, lost to 
follow-up, death and 
documentation 
To clarify early 
withdrawal categories 
11.1. Data Collection;  
11.4.5. Follow-Up 
Added definition of 
missed visit and 
ending 36 Month visit 
window 
To clarify missed visit 
definition 
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Revision History 
Revision 
Number 
Release  
Date 
Template 
Number and 
Version 
Section 
Change 
Reason for Change 
12. Statistical 
Considerations 
Various 
To align with updated 
Statistical Analysis 
Plan 
11.3. Informed 
Consent;  
13.2. Data Retention;  
17.1. Statement of 
Compliance 
Replaced reference to 
ICH-GCP with 
ISO14155:2011 
To clarify which GCP 
standards were 
adhered to 
19.2.1. Mesh Exposure 
and Erosion Event 
Classification 
Replaced physical 
exam with pelvic exam 
To clarify exam type 
20. Informed Consent 
Added Boston 
Scientific or designee 
for informed consent 
review 
To clarify informed 
consent review process 
21. Safety Reporting 
Revised section for AE 
definitions and 
reporting timelines 
To clarify definitions 
and reporting timelines 
08/AD 
05 January 
2018* 
90702637 
Rev/Ver AH 
10.2.4. Subject Death;  
11.6. Subject Death;  
11.1. Data Collection; 
21.6. Investigator 
Reporting 
Requirements 
Revised collection of 
death information to 
include all events    
To align with FDA 
Guidance on 522 Post- 
Market Surveillance 
12.1.1.3. Statistical 
Methods; 
12.2.1. Analysis Sets 
 
Added “per protocol” 
group to primary 
safety endpoint 
evaluation 
To clarify evaluation 
of the primary safety 
endpoint  
12.3.5.4. Subjects with 
surgical intervention for 
recurrence or 
complications 
Added section 
To specify the analysis 
of adverse events by 
vaginal compartment 
after re-surgery 
09/AE 
20 March 
2018 
90702637 
Rev/Ver AH 
11.1. Data Collection;  
11.4.5. Follow-Up 
Increased window for 
follow-up visits to 
occur 
To reduce number of 
late visits 
11.4.5. Follow-Up 
Provide option for 
completion of home or 
phone follow-up visits; 
revised start day for 
visit window 
calculation    
To improve collection 
of follow-up visit data 
and correct error in 
calculation of visit 
windows  
12.1.1.3. Statistical 
Methods 
Added tipping point 
analysis 
To clarify the 
sensitivity analyses to 
be performed 
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Revision History 
Revision 
Number 
Release  
Date 
Template 
Number and 
Version 
Section 
Change 
Reason for Change 
12.2.3. Propensity 
Score Methodology 
Added definition of 
treatment arms 
To clarify how logistic 
regression will be 
performed 
12.3.8. Interim Analysis Added details of 
interim analysis of 12 
month outcomes 
Requested by FDA 
* Not released to the study sites. 
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2. 
Protocol Synopsis 
Postmarket Study PS120081:  A Prospective, Non-Randomized, Parallel 
Cohort, Multi-Center Study of Xenform vs. Native Tissue for the 
Treatment of Women with Anterior/Apical Pelvic Organ Prolapse 
Study 
Objective(s) 
The purpose of this study is to compare transvaginal repair with a 
biologic graft to traditional native tissue repair in women surgically 
treated for anterior and/or apical pelvic organ prolapse.   This study is 
being conducted in partnership with the American Urogynecologic 
Society (AUGS) under the Pelvic Floor Disorders Outcome Registry 
(PFD Registry).   
Test Device 
Xenform Soft Tissue Repair Matrix biologic graft (“Xenform”) 
Control Device 
Traditional native repair (sacrospinous ligament fixation or uterosacral 
ligament suspension and/or colporrhaphy) 
Study Design 
Non-randomized, parallel cohort, multi-center study.   
All procedures will be standardized for uniformity.  Physicians will 
have to document a minimum of 10 procedures with either Xenform or 
a similar biologic graft or with native tissue repair prior to study 
participation in order to document competency and experience.  
Physician training, specialty, and site procedure location (such as 
private-practice, hospital, academic medical center, etc.) will be 
recorded.  
Concomitant procedures including anterior and posterior vaginal wall 
repair, hysterectomy, and sling placement for stress urinary 
incontinence may be performed, per physician discretion.  Sling 
placement can include a synthetic material, however a concomitant 
anterior or posterior repair cannot include a biologic graft or a synthetic 
implant.  An anterior colporrhaphy may be required for cystocele repair, 
if clinically necessary.  All concomitant procedures performed will be 
recorded.  
Subjects who undergo a medical intervention (surgical or non-surgical) 
to treat recurrence, persistence of pelvic organ prolapse or a treatment 
complication will be followed to 36 months from the initial study 
procedure.   
Planned 
Number of 
Subjects 
Approximately 454 subjects enrolled (227 subjects per arm).  Eligible 
control subjects meeting the study inclusion/exclusion criteria may be 
shared from the PFD Registry. 
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Postmarket Study PS120081:  A Prospective, Non-Randomized, Parallel 
Cohort, Multi-Center Study of Xenform vs. Native Tissue for the 
Treatment of Women with Anterior/Apical Pelvic Organ Prolapse 
Planned 
Number of 
Investigational 
Sites / Countries 
Up to 40 study centers 
Primary 
Effectiveness 
Endpoint(s) 
The primary endpoint of the study is to achieve non-inferiority of 
transvaginal repair with Xenform over native tissue repair at 36 months 
as compared to baseline.  Success will be based on a composite of 
objective and subjective measures, and subjects will be considered a 
surgical success if each of the three criteria is met:   
1. Subjective success is achieved if patient denies symptoms of 
vaginal bulging per PFDI-20 question 3, answering “no” or “yes” 
but “Not at all” bothersome (<2)   
2. Anatomic success (in the operated compartment) 
• Anterior Segment:  Leading edge of prolapse is at or above 
the hymen or POP-Q point Ba ≤ 0    
• Apical Segment: The vaginal apex does not descend more 
than one-half into the vaginal canal (i.e. POP-Q point C ˂  
-1/2 TVL) for multi-compartment prolapse or POP-Q point 
C ≤ 0 for prolapse of the apical compartment alone   
3. No retreatment for POP:  No additional surgical treatment for 
POP in the segment(s) of the vagina treated at the index surgery 
or no pessary use since index surgery (i.e., ‘treated segment’ 
refers to the target compartments in this study, which are the 
anterior and apical compartments) 
Primary Safety 
Endpoint(s) 
A co-primary endpoint of the study is to achieve non-inferiority of 
Xenform to native tissue repair for safety by comparing rates of serious 
device or serious procedure related complications between baseline and 
the 36 month time point.  Serious injury is defined per 21 CFR 803.3, 
i.e., life threatening, results in permanent impairment of a body function 
or permanent damage to a body structure, or injury or illness that 
requires medical or surgical intervention to preclude impairment of a 
body function or permanent damage to a body structure. 
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Postmarket Study PS120081:  A Prospective, Non-Randomized, Parallel 
Cohort, Multi-Center Study of Xenform vs. Native Tissue for the 
Treatment of Women with Anterior/Apical Pelvic Organ Prolapse 
Secondary 
Endpoints 
1. Incidence of Xenform erosion 
2. Incidence of Xenform exposure 
3. Incidence of de novo dyspareunia 
4. Improvement in subject specific outcomes at 36 months compared 
to Baseline (pelvic floor symptoms (PFDI-20), QOL (PFIQ-7), 
sexual functioning (PISQ-12), TOMUS pain scale) 
5. Assessment of subject’s level of improvement, measured by the 
Patient Global Impression of Improvement for Prolapse (PGI-I for 
Prolapse) 
6. Absence of re-intervention or re-surgery for recurrence or 
persistence of POP or mesh exposure/erosion 
7. Surgical success based on the following composite outcome: 
a. Subjective success:  patient denies symptoms of vaginal 
bulging per PFDI-20 question 3, answering “no” or “yes” but 
“Not at all” bothersome (<2) 
b. Anatomic success (in the operated compartment): 
• Anterior Segment:  No anterior prolapse at or 
beyond the hymen or POP-Q point Ba<0 
• Apical Segment:   The vaginal apex does not 
descend more than one-half into the vaginal canal 
(i.e. POP-Q point C < 1/2 TVL) for multi-
compartment prolapse or POP-Q point C ˂ 0 for 
single compartment apical prolapse 
c. No retreatment for POP (treated segment):  No additional 
surgical treatment for POP in the segment(s) of the vagina 
treated at the index surgery or no pessary use since index 
surgery (‘treated segment’ refers to the target compartments in 
this study, which are the anterior and apical compartments)  
8. Device or procedure-related incidence of the following:  pelvic 
pain, infection, vaginal shortening, atypical vaginal discharge, 
neuromuscular problems, vaginal scarring, de novo vaginal 
bleeding, fistula formation and/or de novo voiding dysfunction 
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Postmarket Study PS120081:  A Prospective, Non-Randomized, Parallel 
Cohort, Multi-Center Study of Xenform vs. Native Tissue for the 
Treatment of Women with Anterior/Apical Pelvic Organ Prolapse 
Method of 
Assigning 
Subjects to 
Treatment 
This study is a prospective, non-randomized, parallel cohort, multi-
center study.  Approximately 454 subjects will be enrolled and will 
either receive transvaginal repair with Xenform (treatment) or a native 
tissue repair (control) procedure.  Study centers will either participate to 
enroll only Xenform subjects or only native tissue subjects to reduce 
bias; or a combination of Xenform and native tissue subjects depending 
on subject population and per Boston Scientific’s discretion.   
Follow-up 
Schedule 
Study follow-up duration is for 3 years from primary study procedure: 
• Screening/Enrollment Visit 
• Pre-procedure/Baseline Visit 
• Procedure and Discharge 
• Month 2 Visit 
• Month 6 Visit 
• Month 12 Visit  
• Month 18 Visit 
• Month 24 Visit 
• Month 36 Visit (Primary Endpoint and End of Study) 
Study Duration 
Approximately 3 years (36 months) from last subject enrolled. 
Key Inclusion 
Criteria 
1. Subject is female 
2. Subject is ≥18 years of age 
3. Subject has pelvic organ prolapse with the leading edge at or 
beyond the hymen.   At or beyond the hymen is defined as POP-Q 
scores of Ba ≥ 0 (for prolapse of the anterior compartment alone) or 
C ≥ 0 (for prolapse of the apical compartment alone) or C ≥ -1/2 
TVL and Ba ≥ 0 (for a multi-compartment prolapse that includes 
the anterior and apical compartments) 
4. Subject reports of a bothersome bulge they can see or feel per 
PFDI-20, question 3 response of 2 or higher (i.e. responses of 
“somewhat”, “moderately” or “quite a bit”) 
5. Subject or subject’s legally authorized representative must be 
willing to provide written informed consent 
6. Subject is willing and able to comply with the follow-up regimen 
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Postmarket Study PS120081:  A Prospective, Non-Randomized, Parallel 
Cohort, Multi-Center Study of Xenform vs. Native Tissue for the 
Treatment of Women with Anterior/Apical Pelvic Organ Prolapse 
Key Exclusion 
Criteria 
1. Subject is pregnant or intends to become pregnant during the study 
2. Subject has an active or chronic systemic infection including any 
gynecologic infection, untreated urinary tract infection (UTI) or 
tissue necrosis 
3. Subject has history of pelvic organ cancer (e.g. uterine, ovarian, 
bladder, colo-rectal or cervical) 
4. Subject has had prior or is currently undergoing radiation, laser 
therapy, or chemotherapy in the pelvic area 
5. Subject has taken systemic steroids (within the last month), or 
immunosuppressive or immunomodulatory treatment (within the 
last 3 months) 
6. Subject has systemic connective tissue disease (e.g. scleroderma, 
systemic lupus erythematosus (SLE), Marfan syndrome, Ehlers 
Danlos, collagenosis, polymyositis, polymyalgia rheumatica) 
7. Subject has chronic systemic pain that includes the pelvic area or 
chronic focal pain that involves the pelvis  
8. Subject has uncontrolled diabetes mellitus (DM) 
9. Subject has a known neurologic or medical condition affecting 
bladder function (e.g., multiple sclerosis, spinal cord injury or 
stroke with residual neurologic deficit) 
10. Subject is seeking obliterative vaginal surgery as treatment for 
pelvic organ prolapse (colpocleisis) 
11. Subject is not able to conform to the modified dorsal lithotomy 
position  
12. Subject is currently participating in or plans to participate in another 
device or drug study during this study 
13. Subject has a known sensitivity to any Xenform component 
14. Subject has had previous prolapse repair with mesh in the target 
compartment 
15. Subject is planning to undergo a concomitant prolapse repair with 
use of mesh in the non-target compartment 
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Postmarket Study PS120081:  A Prospective, Non-Randomized, Parallel 
Cohort, Multi-Center Study of Xenform vs. Native Tissue for the 
Treatment of Women with Anterior/Apical Pelvic Organ Prolapse 
Statistical Methods  
Primary 
Statistical 
Hypothesis 
Transvaginal repair with Xenform will be non-inferior to traditional 
native tissue repair in effectiveness and non-inferior in safety.   
Non-inferiority testing for effectiveness will be performed for the 
primary hypothesis.    
Statistical testing will be performed to determine if composite endpoint 
of anatomic and symptomatic success rate in transvaginal biologic 
repair (treatment) group will be non-inferior to traditional native tissue 
repair (control) group.  The null hypothesis is that the success rate in 
treatment group is less than or equal to the success rate in control group 
minus margin: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≤− ∆  
 
The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡− 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐> − ∆     
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the success rate in treatment group 
and control group respectively, and ∆ >0 is defined as the non-
inferiority margin.  
Statistical testing will be performed to determine if the serious device-
related or serious procedure-related complication rate of treatment 
group is non-inferior to the control group. The null hypothesis is that the 
complication rate in treatment group is greater than or equal to the rate 
in control group plus margin: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≥∆   
The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < ∆   
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the overall complication rate in 
treatment group and control group respectively, and ∆ >0 is defined as 
the non-inferiority margin. 
Statistical Test 
Method 
All statistical analyses will be performed by Boston Scientific per the 
Statistical Analysis Plan.  All analyses will be done using SAS (version 
8.0 or higher) statistical software.  Subject summary tables and data 
listings will be provided for the data collected.   
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Postmarket Study PS120081:  A Prospective, Non-Randomized, Parallel 
Cohort, Multi-Center Study of Xenform vs. Native Tissue for the 
Treatment of Women with Anterior/Apical Pelvic Organ Prolapse 
Sample Size 
Parameters 
The statistical power calculation is based on a non-inferiority 
assumption with a binary primary outcome. Success, based on a 
composite endpoint of anatomic and symptomatic success at 36 month 
is assumed to be 70%5-8, 16 for the native tissue arm.  With type I error 
of 0.05 and type II error of 0.20 (power 80%), 362 subjects (181 
subjects per arm) are needed to detect non-inferiority of transvaginal 
biologic to native tissue repair, using a margin of 12.0%.   
To assess for safety, the overall complication rate (i.e., serious device-
related or serious procedure-related adverse events) is anticipated to be 
approximately 14%.9  With type I error of 0.05 and type II error of 0.10 
(power 90%), 308 subjects (154 subjects per arm) are needed to detect 
non-inferiority with a margin of 11.6%.   
The rate of device or procedure related de novo dyspareunia is 
anticipated to be approximately 9%.17  With type I error of 0.05 and 
type II error of 0.20 (power 80%), 326 subjects (163 subjects per arm) 
are needed to detect non-inferiority with a margin of 7.9%. 
The rate of device or procedure related AE incidence (pelvic pain, 
infection, vaginal shortening, atypical vaginal discharge, neuromuscular 
problems, vaginal scarring, de novo vaginal bleeding, fistula formation 
and/or de novo voiding dysfunction) is anticipated to be approximately 
12%.15-18  With type I error of 0.05 and type II error of 0.20 (power 
80%), 330 subjects (165 subjects per arm) are needed to detect non-
inferiority with a margin of 8.9%.  
To assess for office-based interventions for complications, the rate is 
anticipated to be approximately 2%.9 With type I error of 0.025 and 
type II error of 0.10 (power 90%), 330 subjects (165 subjects per arm) 
are needed to detect non-inferiority with a margin of 5%.   
To assess for surgical intervention for complications, the rate is 
anticipated to be approximately 1%.9  With type I error of 0.025 and 
type II error of 0.10 (power 90%), 260 subjects (130 subjects per arm) 
are needed to detect non-inferiority with a margin of 4%.   
Non-surgical subjects will not be enrolled in this study as all data on 
this cohort of subjects will be obtained from the AUGS PFD Registry 
and analyzed with data from this clinical study. 
Assuming a 20% loss to follow-up rate, a total of 454 subjects (227 per 
study arm) will be enrolled to achieve the primary endpoint of success 
at 36 months.    
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3. 
Table of Contents 
1. 
TITLE PAGE  ........................................................................................................................ 1 
2. 
PROTOCOL SYNOPSIS .......................................................................................................... 6 
3. 
TABLE OF CONTENTS ........................................................................................................ 13 
3.1. Table of Tables ....................................................................................................... 17 
4. 
INTRODUCTION ................................................................................................................. 18 
5. 
DEVICE DESCRIPTION ....................................................................................................... 18 
6. 
STUDY OBJECTIVES .......................................................................................................... 19 
7. 
STUDY ENDPOINTS ............................................................................................................ 19 
7.1. Primary Endpoints ................................................................................................. 19 
7.2. Secondary Endpoints ............................................................................................. 19 
8. 
STUDY DESIGN .................................................................................................................. 20 
8.1. Scale and Duration ................................................................................................. 21 
8.2. Treatment Assignment .......................................................................................... 22 
8.2.1. 
Treatment ................................................................................................... 22 
8.2.2. 
Control ....................................................................................................... 22 
9. 
SUBJECT SELECTION ......................................................................................................... 22 
9.1. Study Population and Eligibility ........................................................................... 22 
9.2. Inclusion Criteria ................................................................................................... 23 
9.3. Exclusion Criteria .................................................................................................. 23 
10. SUBJECT ACCOUNTABILITY .............................................................................................. 24 
10.1. Point of Enrollment ................................................................................................ 24 
10.2. Withdrawal ............................................................................................................. 25 
10.2.1. Voluntary Withdrawal ............................................................................... 25 
10.2.2. Involuntary Withdrawal ............................................................................. 25 
10.2.3. Lost to Follow-up ...................................................................................... 25 
10.2.4. Subject Death ............................................................................................. 25 
10.2.5. Documentation of Early Termination ........................................................ 26 
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11. STUDY METHODS .............................................................................................................. 26 
11.1. Data Collection ....................................................................................................... 26 
11.2. Study Candidate Screening ................................................................................... 29 
11.3. Informed Consent .................................................................................................. 29 
11.4. Study Visit Schedule .............................................................................................. 29 
11.4.1. Screening/Enrollment Visit ....................................................................... 29 
11.4.2. Pre-Operative/Baseline Visit ..................................................................... 29 
11.4.3. Surgery (≤ 3 months from Baseline Visit) ................................................. 30 
11.4.4. Discharge ................................................................................................... 30 
11.4.5. Follow-Up .................................................................................................. 31 
11.4.6. Month 2 Visit (±4 Weeks) ......................................................................... 31 
11.4.7. Months 6 (± 4 weeks), 12, 18, 24, 36 Visits (-4/+12 weeks) ..................... 31 
11.5. Re-Intervention/Re-Surgery.................................................................................. 32 
11.6. Subject Death .......................................................................................................... 33 
12. STATISTICAL CONSIDERATIONS ....................................................................................... 33 
12.1. Endpoints ................................................................................................................ 33 
12.1.1. Primary Endpoint ....................................................................................... 33 
12.1.1.1. Hypotheses ................................................................................ 33 
12.1.1.2. Sample Size ............................................................................... 34 
12.1.1.3. Statistical Methods .................................................................... 34 
12.1.2. Secondary Endpoints ................................................................................. 35 
12.1.2.1. Hypotheses ................................................................................ 36 
12.1.2.2. Sample Size ............................................................................... 37 
12.1.2.3. Statistical Methods .................................................................... 37 
12.2. General Statistical Methods .................................................................................. 38 
12.2.1. Analysis Sets .............................................................................................. 38 
12.2.2. Control of Systematic Error/Bias ............................................................... 38 
12.2.3. Propensity Score Methodology .................................................................. 39 
12.3. Data Analyses ......................................................................................................... 40 
12.3.1. Rate of Office-Based Intervention for Recurrence .................................... 40 
12.3.2. Rate of Surgical Intervention for Recurrence ............................................ 40 
12.3.3. Rate of Office-Based Intervention for Complications ............................... 41 
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12.3.4. Rate of Surgical Intervention for Complications ....................................... 41 
12.3.5. Sub-Analysis for Sling Repair and Interventions for Recurrence ............. 42 
12.3.5.1. Subjects with only POP repair and those with sling and 
prolapse repair ........................................................................... 42 
12.3.5.2. Subjects with office-based intervention for recurrence ............ 42 
12.3.5.3. Subjects with surgical intervention for recurrence ................... 43 
12.3.5.4. Subjects with surgical intervention for recurrence or 
complications ............................................................................ 43 
12.3.6. Additional Data Analyses .......................................................................... 43 
12.3.7. Sub-Analysis for Interventions for Complications .................................... 43 
12.3.8. Interim Analysis ......................................................................................... 43 
12.3.8.1. Hypotheses ................................................................................ 44 
12.3.8.2. Statistical Methods .................................................................... 44 
12.3.9. Justification of Pooling .............................................................................. 45 
12.3.10. Multivariable Analyses .............................................................................. 45 
13. DATA MANAGEMENT ........................................................................................................ 45 
13.1. Data Collection, Processing, and Review ............................................................. 45 
13.2. Data Retention ........................................................................................................ 46 
14. AMENDMENTS ................................................................................................................... 46 
15. DEVIATIONS ...................................................................................................................... 46 
16. DEVICE/EQUIPMENT ACCOUNTABILITY .......................................................................... 47 
17. COMPLIANCE ..................................................................................................................... 47 
17.1. Statement of Compliance ....................................................................................... 47 
17.2. Investigator Responsibilities ................................................................................. 47 
17.2.1. Delegation of Responsibility ..................................................................... 49 
17.3. Institutional Review Board/ Ethics Committee ................................................... 49 
17.4. Sponsor Responsibilities ........................................................................................ 49 
17.5. Insurance ................................................................................................................. 50 
18. MONITORING ..................................................................................................................... 50 
19. POTENTIAL RISKS AND BENEFITS .................................................................................... 50 
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19.1. General .................................................................................................................... 50 
19.2. Anticipated Adverse Events .................................................................................. 51 
19.2.1. Xenform Exposure and Erosion Event Classification ............................... 52 
19.3. Risks Associated with Participation in the Clinical Study ................................. 52 
19.4. Risk Minimization Actions .................................................................................... 52 
19.5. Anticipated Benefits ............................................................................................... 52 
19.6. Risk to Benefit Rationale ....................................................................................... 52 
20. INFORMED CONSENT ......................................................................................................... 53 
21. SAFETY REPORTING .......................................................................................................... 54 
21.1. Reportable Events by Investigational Site to Boston Scientific ......................... 54 
21.2. Definitions and Classification ............................................................................... 54 
21.3. Relationship to Study Device (Xenform Cohort Only) ....................................... 55 
21.4. Relationship to Study Procedure .......................................................................... 56 
21.5. Relationship to Pelvic Floor .................................................................................. 56 
21.6. Investigator Reporting Requirements .................................................................. 57 
21.7. Boston Scientific Device Deficiencies .................................................................... 59 
21.8. Reporting to Regulatory Authorities / IRBs / ECs / Investigators .................... 59 
22. COMMITTEES .................................................................................................................... 59 
22.1. Safety Monitoring Process ..................................................................................... 59 
23. SUSPENSION OR TERMINATION ......................................................................................... 59 
23.1. Premature Termination of the Study ................................................................... 59 
23.1.1. Criteria for Premature Termination of the Study ....................................... 60 
23.2. Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC Approval .................................................................................................. 60 
23.3. Requirements for Documentation and Subject Follow-up ................................. 60 
23.4. Criteria for Suspending/Terminating a Study Center ........................................ 60 
24. PUBLICATION POLICY ....................................................................................................... 61 
25. REFERENCES ..................................................................................................................... 62 
 
 
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3.1. 
Table of Tables 
Table 10.1-1: Study Timeline ................................................................................................. 24 
Table 11.1-1: Data Collection Schedule ................................................................................. 27 
Table 11.1-2: Data Collection Schedule for Subjects Requiring a Re-Surgery ...................... 28 
Table 21.2-1: Adverse Event Definitions ............................................................................... 55 
Table 21.3-1: Criteria for Assessing Relationship of Study Device to Adverse Event .......... 56 
Table 21.4-1: Criteria for Assessing Relationship to Study Procedure .................................. 56 
Table 21.5-1: Criteria for Assessing Relationship to Pelvic Floor ......................................... 57 
Table 21.6-1: Investigator Reporting Requirements ............................................................... 57 
 
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4. 
Introduction 
Pelvic organ prolapse (POP) of the anterior and posterior vaginal wall, and vaginal apex, are 
among the most challenging and common aspects of traditional pelvic reconstructive surgery.  
As life expectancy increases, significantly greater numbers of women will present with POP 
and stress urinary incontinence (SUI) requiring surgical intervention.  Women face an 11% 
lifetime risk of requiring major surgery for POP.3   
The main goal of POP surgery is restoration of normal anatomy to achieve proximal vaginal 
suspension, mid-vaginal lateral attachments and distal vaginal fusion to the urogenital fascia 
and perineum.  Women undergoing pelvic reconstructive surgery for POP hope to achieve 
relief of symptoms, restoration of normal anatomy, maintenance of vaginal capacity for 
sexual function and improvement in the quality of life. 
The difficulties associated with repair of cystocele were cited by Ahfelt as early as 1909, and 
reinforced nearly a century later by Weber et al. (2001) who reported recurrence rates as high 
as 70% in a widely cited randomized controlled study (RCT).4  Clark et al. estimated that up 
to 60% of surgical recurrences occur at the same anatomic site as the original repair, 
highlighting the limitations associated with plicating and/or suspending weakened connective 
tissues to one another.1  In recent years, surgical methods such as vaginal mesh repair (VMR) 
have become available as an option for treating more advanced and challenging cases. 
Biologic grafts like Xenform offer potential advantages over synthetic meshes.  These 
include the capability for in-vivo tissue remodeling and consequent reduction in the rates of 
extrusion and/or erosion10.  Goldstein, et al.2 studied Xenform and showed an 88% success 
rate when patients were followed for one (1) year. 
5. 
Device Description 
Xenform Soft Tissue Repair Matrix is intended for use as a soft tissue patch to reinforce soft 
tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue 
membranes.  Xenform is specifically indicated for the repair of colon, rectal, urethral and 
vaginal prolapse, and procedures such as sacrocolposuspenstion and urethral sling.  
Xenform is derived from fetal bovine dermis.  It is predominantly Type I and Type III 
collagen.  Other versions of the same processed fetal bovine dermal material have been used 
to treat over 250,000 patients in soft tissue repair applications, including repair/replacement 
of the dura, repair/reinforcement of tendons, wound closure, hernia repair and general plastic 
and reconstructive surgery. 
When hydrated, Xenform is pliable, strong and tissue-compatible because it is derived from 
animal tissue.  Xenform is not chemically cross-linked like some other biologic grafts but 
relies on the inherent strength of the bovine dermis from which it is derived.  It is easily 
vascularized and is thought to remodel into a native tissue-like structure. 
Xenform has been used in over 30,000 patients, worldwide, and there have been no 
complaints of tissue erosion, tissue perforation, or infection to-date. 
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6. 
Study Objectives 
The primary objective is to evaluate clinical effectiveness of transvaginal repair with 
Xenform against traditional native tissue repair in women surgically treated for anterior 
and/or apical pelvic organ prolapse.  Secondary objectives are to evaluate Xenform-related 
complications and subject reported outcomes.  
7. 
Study Endpoints 
7.1. 
Primary Endpoints 
The primary endpoint of the study is to achieve non-inferiority of transvaginal repair with 
Xenform over native tissue repair at 36 months as compared to baseline.   
Success will be based on a composite of objective and subjective measures, and subjects will 
be considered a surgical success if each of the three criteria is met:   
1. Subjective success is achieved if the patient denies symptoms of vaginal bulging per 
PFDI-20 question 3, answering “no” or “yes” but “Not at all” bothersome (<2). 
2. Anatomic success (in the operated compartment): 
• Anterior segment:  Leading edge of anterior prolapse is at or above the hymen 
or POP-Q point Ba ≤ 0. 
• Apical segment:  The vaginal apex does not descend more than one-half into 
the vaginal canal (i.e. POP-Q point C < -1/2 TVL) for multi-compartment 
prolapse or POP-Q point C ≤ 0 for single compartment apical prolapse. 
3. No retreatment for POP:  No additional surgical treatment for POP in the segment(s) 
of the vagina treated at the index surgery or no pessary use since index surgery (i.e., 
‘treated segment’ refers to the target compartments in this study, which are the 
anterior and apical compartments). 
Additionally, a co-primary endpoint of the study is to achieve non-inferiority of transvaginal 
repair with Xenform to native tissue repair for safety by comparing rates of serious device or 
serious procedure related complications between baseline and the 36 month time point. 
Serious injury is defined per 21 CFR 803.3, i.e., life threatening, results in permanent 
impairment of a body function or permanent damage to a body structure or injury or illness 
that requires medical or surgical intervention to preclude impairment of a body function or 
permanent damage to a body structure.  
7.2. 
Secondary Endpoints 
The secondary endpoints of the study include assessments of complications and subject 
reported outcomes: 
1. Incidence of mesh erosion  
2. Incidence of mesh exposure 
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3. Incidence of de novo dyspareunia 
4. Improvement in subject-related outcomes at 36 months compared to Baseline ((pelvic 
floor symptoms (PFDI-20), QOL (PFIQ-7), sexual functioning (PISQ-12) TOMUS 
pain scale) 
5. Assessment of subject’s level of improvement, measured by the Patient Global 
Impression of Improvement for Prolapse (PGI-I for Prolapse) 
6. Absence of re-intervention and re-surgery for recurrence of POP, persistence of 
disease, or Xenform exposure/erosion 
7.  Surgical success based on the following composite outcome: 
a. Subjective success:  patient denies symptoms of vaginal bulging per PFDI-20 
question 3, answering “no” or “yes” but “Not at all” bothersome (<2) 
b. Anatomic success (in the operated compartment): 
• Anterior Segment:  No anterior prolapse at or beyond the hymen or 
POP-Q point Ba<0 
• Apical Segment:  The vaginal apex does not descend more than one-
half into the vaginal canal (i.e., POP-Q point C ˂ 1/2 TVL) for multi-
compartment prolapse or POP-Q point C ˂ 0 for prolapse of the apical 
compartment alone. 
c. No retreatment for POP (treated segment):  No additional surgical treatment 
for POP in the segment(s) of the vagina treated at the index surgery or no 
pessary use since index surgery (‘treated segment’ refers to the target 
compartments in this study, which are the anterior and apical compartments) 
8. Incidence of the following device or procedure-related AEs:  pelvic pain, infection, 
vaginal shortening, atypical vaginal discharge, neuromuscular problems, vaginal 
scarring, de novo vaginal bleeding, fistula formation and/or de novo voiding 
dysfunction 
8. 
Study Design 
This study is a prospective, non-randomized, parallel cohort, multi-center study conducted in 
partnership with the AUGS PFD Registry.   
The primary endpoint will be assessed once all per protocol subjects have completed the 36 
month study visit.  All per protocol subjects will be followed to month 36, until study 
completion, or until discontinuation prior to month 36.  All study procedures will be 
standardized for uniformity.  Prior to enrolling a subject, physicians must have completed a 
minimum of 10 procedures (defined for each arm) in order to document competency and 
experience.  For the native tissue arm, physicians must have completed a minimum of 10 
transvaginal anterior-apical prolapse repair procedures that incorporate an apical vault 
suspension utilizing either a uterosacral ligament suspension or sacrospinous ligament 
fixation.  For the Xenform arm, physicians must have completed a minimum of 10 native 
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tissue repair procedures (as defined for the native tissue arm) augmented with a biologic graft 
or Xenform, and the uterosacral and/or sacrospinous ligaments must be accessed via the 
anterior compartment incision.  Physician training, specialty, and site procedure location 
(such as private-practice, hospital, academic medical center, etc.) will be recorded.  
All efforts will be made to ensure all follow-up anatomic measurements (POP-Q) will be 
assessed by a healthcare provider to reduce surgeon bias on outcomes after the index 
procedure. In the event the treating surgeon is the only qualified healthcare provider at the 
site trained in POP-Q assessments, the follow-up anatomic measurements will be performed 
by the treating surgeon. 
All enrolled subjects will have an anterior and/or apical defect.  Concomitant procedures to 
treat a secondary defect can occur (including an anterior repair, posterior repair, 
hysterectomy, or sling placement for stress urinary incontinence) at the time of prolapse 
repair for the primary defect, per physician discretion.  Sling placement may include a 
synthetic material yet a concomitant anterior repair or posterior repair cannot include a 
biologic graft or a synthetic implant.  An anterior colporrhaphy may be required, if clinically 
necessary.  All concomitant procedures performed will be recorded.  
Subjects who undergo a medical intervention (surgical or non-surgical) to treat recurrence, 
persistence of POP, or Xenform or suture complication will be followed to month 36 from 
the initial study procedure.  
8.1. 
Scale and Duration 
The study will be conducted at up to 40 sites at a rate of approximately 2 subjects per site, 
per month.  Sites will be encouraged to enroll a minimum of 15 subjects and up to a 
maximum of 50 subjects.   
It is anticipated that approximately 454 subjects will be enrolled in total to achieve 362 
subjects (181 subjects per treatment arm) for the primary endpoint analysis at 36 months 
post-surgery to achieve non-inferiority of repair with Xenform to native tissue repair for 
effectiveness by comparing rates based on a composite endpoint of anatomic and 
symptomatic success between baseline and the 36 month time point.  Due to the partnership 
with the PFD Registry, it is anticipated a portion of the control arm subjects will be shared 
from the Registry.   
The enrollment period is expected to be approximately 12 to 18 months after the final study 
center has been permitted to enroll subjects.  A potential 20% “lost to follow-up” rate is 
anticipated.   
Once enrolled into the study, subjects will be followed to 36 months post-surgery to be 
evaluated for the primary endpoint analysis.  The total duration of each subject’s 
participation in the study is 36 months from time of procedure.  
Subjects who undergo a medical intervention (surgical or non-surgical) to treat recurrence, 
persistence of POP, or Xenform or suture complication will be followed to 36 months, post 
the initial study procedure.  
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8.2. Treatment Assignment 
This post-approval study is a prospective, non-randomized, parallel cohort study across 
multiple centers.  Subjects will be screened against the study Inclusion/Exclusion criteria and 
if eligible, enrolled into the study after providing Informed Consent.   
Study centers will be selected by Boston Scientific to perform the study procedure as either a 
treatment center or a control center, depending on experience to reduce selection bias.  Some 
study centers may be selected to enroll a combination of treatment and control subjects, 
depending on subject population and per Boston Scientific discretion.   
Treatment will occur after all Baseline procedures have been completed and the subject has 
been deemed eligible for the study.  Baseline procedures may be combined with the 
screening visit and may occur within three months prior to the study procedure, with 
confirmation of no evidence of infection prior to the procedure.  Due to the allowable 
window of up to three months between baseline and study procedure, the study staff will 
confirm that subjects are still electing to undergo the study surgery with confirmation of no 
evidence of infection.  
8.2.1. 
Treatment 
The treatment device in this study is the Xenform® Soft Tissue Repair Matrix (“Xenform”).  
Please refer to the Directions for Use document for device-specific information.  The 
Xenform surgical procedure will be standardized across all centers for uniformity through the 
application of step-by-step instructions for placement.  Physicians will be trained to the 
standardized procedure steps prior to the first study procedure being performed.  Minor 
modifications to the standardization may be necessary based on a physician’s practice and 
patient care. 
8.2.2. 
Control 
The control procedure in this study is traditional native tissue repair, which includes 
sacrospinous ligament fixation or uterosacral ligament suspension and/or anterior 
colporrhaphy.  The surgical procedure will be standardized, including suture type (delayed 
absorbable or permanent sutures). Sacrospinous ligament fixation may be performed if the 
uterosacral ligaments are deemed unusable due to scarring or inability to access. 
9. 
Subject Selection  
9.1. 
Study Population and Eligibility  
This study will enroll adult, non-pregnant women who have been diagnosed with anterior 
and/or apical pelvic organ prolapse and will undergo repair surgery, and who may or may not 
also undergo a concomitant procedure (such as anterior repair, posterior repair, hysterectomy, 
or sling placement for stress urinary incontinence).  If a concomitant procedure were to occur 
at the time of the index prolapse repair, the sling placement should be a synthetic material, 
however the concomitant anterior or posterior repair cannot include a biologic graft or 
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synthetic implant.  An anterior colporrhaphy may be performed for cystocele repair, if 
clinically necessary.   
To assess for eligibility for this study, inclusion and exclusion criteria are included in 
Sections 9.2 and 9.3 below. 
9.2. 
Inclusion Criteria 
Subjects who meet all of the following criteria may be given consideration for inclusion in 
this clinical investigation, provided no exclusion criterion (see Section 9.3) is met. 
1. Subject is female 
2. Subject is ≥18 years of age 
3. Subject has pelvic organ prolapse with the leading edge at or beyond the hymen. At 
or beyond the hymen is defined as POP-Q scores of Ba≥ 0 (for prolapse of the 
anterior compartment alone) or C≥ 0 (for prolapse of the Apical compartment alone) 
or C≥ -1/2 TVL and Ba≥ 0 (for multi-compartment prolapse that includes the anterior 
and apical compartments) 
4. Subject reports of a bothersome bulge they can see or feel per PFDI-20, question 3 
response of 2 or higher (i.e. responses of “somewhat”, “moderately”, or “quite a bit) 
5. Subject or subject’s legally authorized representative must be willing to provide 
written informed consent 
6. Subject is willing and able to comply with the follow-up regimen 
9.3. 
Exclusion Criteria 
Subjects who meet any one of the following criteria will be excluded from this clinical study. 
1. Subject is pregnant or intends to become pregnant during the study 
2. Subject has an active or chronic systemic infection including any gynecologic 
infection, untreated urinary tract infection (UTI) or tissue necrosis 
3. Subject has a history of pelvic organ cancer (e.g. uterine, ovarian, bladder, colo-rectal 
or cervical) 
4. Subject has had prior or is currently undergoing radiation, laser therapy, or 
chemotherapy in the pelvic area 
5. Subject has taken systemic steroids (within the last month), or immunosuppressive or 
immunomodulatory treatment (within the last 3 months) 
6. Subject has a systemic connective tissue disease (e.g. scleroderma, systemic lupus 
erythematosus (SLE), Marfan Syndrome, Ehlers Danlos, collagenosis, polymyositis, 
polymyalgia rheumatica) 
7.  Subject has chronic systemic pain that includes the pelvic area or chronic focal pain 
that involves the pelvis 
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8. Subject has uncontrolled diabetes mellitus (DM) 
9. Subject has a known neurologic or medical condition affecting bladder function (e.g., 
multiple sclerosis, spinal cord injury or stroke with residual neurologic deficit) 
10. Subject is seeking obliterative vaginal surgery as treatment for pelvic organ prolapse 
(colpocleisis) 
11. Subject is not able to conform to the modified dorsal lithotomy position  
12. Subject is currently participating in or plans to participate in another device or drug 
study during this study 
13. Subject has a known sensitivity to any Xenform component 
14. Subject has had previous prolapse repair with mesh in the target compartment 
15. Subject is planning to undergo a concomitant prolapse repair with use of mesh in the 
non-target compartment 
10. Subject Accountability 
10.1. Point of Enrollment 
Subjects will be considered enrolled in the study once an incision is made in the vaginal wall. 
All enrolled subjects will have been consented and assigned to receive either the treatment or 
control procedure per site assignment.  Per Boston Scientific’s discretion, a site may be 
considered for participation in both the treatment and control procedure arms however each 
physician must be designated to one arm only.  All enrolled subjects with a surgery initiated 
(i.e. incision in vagina) will be considered part of the Intent-to-Treat (ITT) population for the 
final study analysis.  All ITT subjects who are treated with a study procedure and had no 
major protocol deviations will be considered part of the Per Protocol analysis.      
The following study timeline (see Table 10.1-1) is based on milestones completed and the 
current follow-up visit cadence.    
Table 10.1-1: Study Timeline 
Study Milestones 
Dates  
Final FDA Approved Protocol 
September 2013 
First Site Initiated or Enrollment Ready 
January 2014 
Last Site Initiated or Enrollment Ready 
December 2014 
First Subject Enrolled 
February 2014 
Last Subject Enrolled 
December 2016 
Expected Date of Subject Follow-up Complete 
December 2019 
Expected Date of Final Database Lock/Study Completion 
February 2020  
Expected Date of Final Report Submission to FDA 
June 2020 
 
All efforts will be made by site staff to ensure minimal loss to follow-up of patients and will 
follow a site-specific loss to follow-up plan.  The plan may include efforts such as telephone 
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follow-up, Investigator-patient counseling, visit reminder tools, patient stipends if permitted 
per site IRB, and/or other communication methods.   
10.2. Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study 
or lost to follow-up) will be accounted for and documented. If a subject withdraws from the 
clinical investigation, the reason(s) will be recorded. Reasons for study withdrawal may 
include voluntary withdrawal (withdrew consent), involuntary withdrawal, lost to follow-up, 
death or other reasons to be documented in the Case Report Form.     
10.2.1. Voluntary Withdrawal 
Subjects may withdraw from the study at any time.  At the time of withdrawal, the 
Investigator shall document the reason for the withdrawal. For subjects who withdraw from 
the study and decide to revoke their authorization to use and disclose their medical 
information, the information that has already been collected in the study record may continue 
to be used; however, no new information will be obtained or added.   
10.2.2. Involuntary Withdrawal  
Subjects may be involuntarily withdrawn from the study if the Investigator determines it is in 
the subject’s best interest.   
10.2.3. Lost to Follow-up 
Before a subject may be considered lost to follow-up the Investigator must make the 
following attempts to contact the subject: 
• Two documented telephone attempts  
• One certified letter  
If the subject is able to be reached and no longer wishes to participate in the study the 
Investigator shall document the reason for the withdrawal and complete End of Study Case 
Report Form.  If the subject is not able to be reached after the required attempts to contact the 
subject are made and the subject has missed two consecutive follow-up visits within a 12 
month calendar period, the subject may be considered lost to follow-up.  The Investigator 
should document in the subject’s medical record the attempts to contact the subject and 
reason for the withdrawal. 
10.2.4. Subject Death 
Subjects may be withdrawn from the study in the event of a death.  If any serious adverse 
event results in death (regardless of the relatedness to the study device, procedure or pelvic 
floor), the event is to be documented in the source documentation, Case Report Form, and 
reported to Boston Scientific within the timeframe noted in Table 21.6-1 (Investigator 
Reporting Requirements).  If an autopsy is conducted, a copy of the final autopsy report 
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should be submitted to Boston Scientific or designee.  The primary objective of the autopsy 
is to determine the cause of death, complications and other relevant findings.  The 
investigator will complete an End of Study Case Report Form and an adverse event (if 
applicable) per Section 11.6.   
10.2.5. Documentation of Early Termination  
Once a subject withdraws from the study, the Case Report Form will be completed as 
appropriate up to the point of withdrawal and all Adverse Events shall be closed or 
documented as appropriate.  Withdrawn subjects (who had the study procedure initiated) will 
be included in the Intent-to-Treat analysis and will not be replaced. 
11. Study Methods 
11.1. Data Collection 
Study data will be collected per the schedule outlined in Table 11.1-1.  All study data will be 
recorded on source documentation and captured within Case Report Forms for the purposes 
of this study.  Study data will be monitored by Boston Scientific or representatives and as 
applicable on a regular basis as outlined in the study Monitoring Plan. 
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Table 11.1-1: Data Collection Schedule 
Procedure/Assessment 
Screening/ 
Enrollment Visit2 
Pre-Operative/ 
Baseline Visit 
 
Surgery 
(≤3 mos from 
Baseline) 
Discharge 
Post-Operative Follow-up Visits7 
Month 2 Visit 
(± 4 Weeks) 
Month 6 Visit 
(± 4 weeks) 
Month 12 Visit 
(-4/+12 weeks) 
Month 18 Visit 
(-4/+12 weeks) 
Month 24 Visit 
(-4/+12 weeks) 
Month 36* Visit 
(-4/+12 weeks) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria Review 
X 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
Urine Pregnancy Test 
X 
X 
 
 
 
 
 
 
 
 
Physical Examination 
 
X 
 
 
 
 
 
 
 
 
Medical History1 
 
X 
 
 
 
 
 
 
 
 
Pelvic Exam with vaginal length 
measurement  
 
X 
 
 
X 
X 
X 
X 
X 
X 
Assessment of Infection (vaginal, bladder) 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Prolapse Grading (POP-Q Scoring) 
 
X 
 
 
X 
X 
X 
X 
X 
X 
PFDI-20 (Pelvic Floor Symptoms) 
 
X 
 
 
X 
X 
X 
X 
X 
X 
PFIQ-7 (Quality of Life) 
 
X 
 
 
 
X 
X 
X 
X 
X 
PISQ-12 (Sexual Functioning) 
 
X 
 
 
 
X 
X 
X 
X 
X 
PGI-I for Prolapse (Patient 
Improvement) 
 
 
 
 
 
X 
X 
X 
X 
X 
TOMUS Pain Scale 
 
X 
 
 
X 
X 
X 
X 
X 
X 
SSQ-8 for Surgical Satisfaction 
 
 
 
 
 
X 
X 
 
X 
X 
EQ-5D for Health Status 
 
X 
 
 
 
 
X 
 
X 
X 
Procedure and Assessments3 
 
 
X 
 
 
 
 
 
 
 
Post-Operative Assessment4 
 
 
 
X 
 
 
 
 
 
 
Assessment of Analgesic Intake 
 
X 
 
 
X 
X 
X 
X 
X 
X 
Assessment of Adverse Events6 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of Risk Factors5 
 
X 
 
 
X 
X 
X 
X 
X 
X 
End of Study 
 
 
 
 
 
 
 
 
 
X 
*Primary Endpoint 
1Medical History at baseline includes documented absence of UTI or other vaginal infection (i.e. vaginal culture, etc.). 
2The Screening/Enrollment Visit and Pre-Operative/Baseline Visit may be combined and occur up to 3 months prior to the study procedure with confirmed absence of infection. 
3Assessments include cystoscopy (at discretion of surgeon), estimated blood loss (EBL), assessment of concomitant procedures, and assessment of anesthesia type and duration of procedure. 
4Post-Operative Assessments include assessment of infection (wound, vaginal, bladder), voiding status, and date and time of discharge.   
5Assessment of Risk Factors includes menopausal status, estrogen use, age, smoking, diabetes status, BMI, hysterectomy status, concomitant procedures, surgeon training and experience. 
6All serious and non-serious device, procedure, and pelvic floor-related events, any other relevant events pertaining to the pelvic region, and any events resulting in death will be collected. 
7Every effort should be made to do the follow-up visit within the window; however, if this is not possible, the site should attempt to complete the visit as soon as possible but before the next 
visit window opens.  Follow-up visits will be considered missed once the visit window for the next follow-up visit opens.  For the Month 36 visit, the visit is not considered missed until the last 
day of the visit window. 
 
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If a subject requires a re-surgery during the study, please refer to the reduced table below for follow-up assessments.  Subjects 
undergoing re-interventions (non-surgical) continue with the study schedule as noted in Table 11.1-1.  Additional data will be 
collected on subjects requiring a re-surgery, including a second procedure, Xenform removal (as applicable), and second hospital 
discharge. All subjects who are re-operated on will continue with their follow-up schedule until 36 months post their initial study 
procedure.    
Table 11.1-2: Data Collection Schedule for Subjects Requiring a Re-Surgery 
Procedure/Assessment 
Screening/ 
Enrollment 
Visit 
Pre-
Operative/ 
Baseline 
Visit 
Surgery  
(≤3 mos 
from 
Baseline) 
Discharge 
Post-Operative Follow-up Visits (± 4 Weeks) 
Month  2 Visit 
(± 4 Weeks) 
Re-Surgery 
Discharge 
Next Scheduled  
Follow-up Visit  
(-4/+12 Weeks) 
Month 36 
Visit* 
(-4/+12 
weeks) 
Informed Consent 
X 
 
 
 
 
 
 
After a re-surgery, 
subjects will return to the 
clinic on the date of their 
next regular study visit 
per the Schedule of 
Events table above.  
Subjects will continue to 
return for all scheduled 
Follow-up Visits until 36 
months post their initial 
study procedure. 
 
Inclusion/Exclusion Criteria Review 
X 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
Urine Pregnancy Test 
X 
X 
 
 
 
 
 
 
Physical Examination 
 
X 
 
 
 
 
 
 
Medical History1 
 
X 
 
 
 
 
 
 
Pelvic Exam with vaginal length 
measurement 
 
X 
 
 
X 
 
 
X 
Assessment of infection (vaginal, bladder) 
 
 
 
X 
X 
 
X 
X 
Prolapse Grading (POP-Q Scoring) 
 
X 
 
 
X 
 
 
X 
PFDI-20 (Pelvic Floor Symptoms) 
 
X 
 
 
X 
 
 
X 
PFIQ-7 (Quality of Life) 
 
X 
 
 
 
 
 
X 
PISQ-12 (Sexual Functioning) 
 
X 
 
 
 
 
 
X 
PGI-I for Prolapse (Patient Improvement) 
 
 
 
 
 
 
 
X 
TOMUS Pain Scale 
 
X 
 
 
X 
 
 
X 
SSQ-8 for Surgical Satisfaction 
 
 
 
 
 
 
 
X 
EQ-5D for Health Status 
 
X 
 
 
 
 
 
X 
Procedure and Assessments3 
 
 
X 
 
 
X 
 
 
Post-Operative Assessment4 
 
 
 
X 
 
 
  
 
Assessment of Analgesic Intake 
 
X 
 
 
X 
 
 
X 
Assessment of Adverse Events6 
 
 
X 
X 
X 
X 
X 
X 
Assessment of Risk Factors5 
 
X 
 
 
X 
 
 
X 
End of Study 
 
 
 
 
 
 
 
X 
 
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11.2. Study Candidate Screening 
Potential subjects will be identified by qualified staff at each selected study center as per 
their individual processes that will be documented at either the Site Qualification Visit and/or 
the Site Initiation Visit.   
Subjects will be screened against the inclusion and exclusion criteria, and if confirmed to 
meet all requirements will be eligible to be consented for enrollment into the study.   
Subjects who do not meet the inclusion and exclusion criteria and/or are not enrolled into the 
study are considered screening failures.  Information on screen failure subjects will be 
captured in the source documentation and screening logs and should include reasons for 
screen failure. 
11.3. Informed Consent 
Prior to any study-related assessments, each subject must sign an IRB-approved informed 
consent document to participate in the study as described in the Declaration of Helsinki and 
ISO 14155:2011 (Clinical investigation of medical devices for human subjects - Good 
clinical practice) and will be in accordance with all applicable laws and regulations.  The 
informed consent form will describe the planned and permitted uses, transfers, and 
disclosures of the subject’s personal health information. 
The subject or legally authorized representative (if approved by the IRB) will be given ample 
opportunity to inquire about details of the study to decide whether or not to participate in the 
study.  Copies of the informed consent form will be provided to the subject and original 
documents filed at each study center as per regulatory requirements. 
Once the subject voluntarily agrees to participate in the study, then the Study Visit Schedule 
will be followed per below and as outlined in Table 11.1-1 (Data Collection Schedule).   
11.4. Study Visit Schedule 
The schedule of assessments is detailed in Table 11.1-1 (Data Collection Schedule). 
11.4.1. Screening/Enrollment Visit 
The Screening/Enrollment visit may occur prior to the Pre-Operative/Baseline visit.  At this 
visit, the assessments below must be completed.   
• Informed consent 
• Review of inclusion/exclusion criteria 
11.4.2. Pre-Operative/Baseline Visit  
The Pre-operative/Baseline Visit will occur prior to the subject having surgery.  The 
assessments below must be completed prior to study surgery.  This visit may be combined 
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with the Screening/Enrollment Visit and occur up to 3 months prior to surgery with 
confirmed absence of infection.  
• Urine pregnancy test 
• Medical history and physical examination:  assessment of urinary tract infection 
(UTI) or other vaginal infection   
• Pelvic examination, vaginal length measurement 
• Prolapse grading (POP-Q scoring) 
• Assess baseline quality of life (PFIQ-7), sexual functioning (PISQ-12), pelvic floor 
symptoms (PFDI-20) 
• Assess baseline level of pain (TOMUS pain scale) and analgesic use 
• EQ-5D for health status 
• Assessment of risk factors (includes menopausal status, estrogen use, age, smoking, 
diabetes status, body mass index, hysterectomy status, concomitant procedures, 
surgeon training and expertise)  
11.4.3. Surgery (≤ 3 months from Baseline Visit) 
All procedures are to be performed with either Xenform or native tissue repair, depending on 
which group the subject has been assigned.  Concomitant procedures including posterior 
repair or sling placement for stress urinary incontinence can occur, per physician discretion.  
All concomitant procedures will be documented.   
• Study procedure  
• Cystoscopy, if clinically necessary 
• Estimated blood loss [i.e., the total blood loss for the index procedure and 
concomitant procedure(s) combined] 
• Documentation of concomitant procedures    
• Document anesthesia type 
• Document duration of procedure [i.e., the total duration for the index procedure and 
concomitant procedure(s) combined]  
• Assessment of adverse events (device, procedure, and pelvic floor related) 
11.4.4. Discharge 
The subject may be discharged from the hospital and/or treatment facility per standard of 
care and/or at the Investigator’s discretion.  Before the subject is discharged, the following 
assessments must be completed.  
• Assessment of infection (wound, vaginal, bladder) 
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• Assessment of voiding status at discharge (i.e., subject discharged with indwelling 
catheter or performing self-catheterization to empty bladder or date/time of first void) 
• Date and time of discharge 
• Assessment of adverse events (device, procedure, or pelvic floor related) 
11.4.5. Follow-Up 
Subjects will be scheduled for follow-up visits as outlined in Table 11.1-1 (Data Collection 
Schedule).  The follow-up visit schedule begins from the day of the study surgery and 
includes visit windows (counted in calendar days). 
Every effort should be made to do the follow-up visit within the window; however, if this is 
not possible, the site should attempt to complete the visit as soon as possible but before the 
next visit window opens.  Follow-up visits will be considered missed once the visit window 
for the next follow-up visit opens.  For the Month 36 visit, the visit is not considered missed 
until the last day of the visit window (i.e., +12 weeks). 
Every effort should be made to conduct the follow-up visit at the study site location.  
However, if the subject cannot physically return to the site for any reason, the follow-up visit 
may be conducted at the subject’s home with their consent and if allowed by local 
institutional policy and the IRB/EC.  If a home visit is not possible, every effort should be 
made to conduct as much of the visit as possible by phone (i.e., assess adverse events, risk 
factors, and analgesic intake) and to send the subject questionnaires by mail for completion.   
11.4.6. Month 2 Visit (±4 Weeks) 
• Pelvic exam with vaginal length measurement  
• Assessment of infection (vaginal, bladder) 
• Prolapse grading (POP-Q Scoring) 
• Assess pelvic floor symptoms (PFDI-20) 
• Assessment of pain (TOMUS pain scale) and analgesic intake 
• Assessment of adverse events (device, procedure, and pelvic floor related) 
• Assessment of risk factors 
11.4.7. Months 6 (± 4 weeks), 12, 18, 24, 36 Visits (-4/+12 weeks) 
• Pelvic exam with vaginal length measurement 
• Assessment of infection (vaginal, bladder) 
• Prolapse grading (POP-Q Scoring) 
• Assessment of pain (TOMUS pain scale) and analgesic intake 
• PFDI-20  
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• PFIQ-7 
• PISQ-12 
• PGI-I for Prolapse 
• SSQ-8 for surgical satisfaction (Months 6, 12, 24, 36 only) 
• EQ-5D for health status (Months 12, 24, 36 only) 
• Assessment of adverse events (device, procedure, and pelvic floor related) 
• Assessment of risk factors 
• Study completion (Month 36 only)  
All subjects who have completed the study surgery and discharge will proceed to be followed 
through the above-outlined study visits to Month 36 where the primary endpoint analysis will 
be achieved when the last subject completes this visit.  All subjects completing the Month 36 
visit will be considered to have completed the study.   
11.5. Re-Intervention/Re-Surgery 
It is the intention of this study to demonstrate an improvement in anterior/apical pelvic organ 
prolapse through clinical effectiveness of transvaginal prolapse repair with Xenform.  
However, it is recognized that during the course of the study, there is a possibility subjects 
may require a medical re-intervention for events including but not limited to failed prolapse 
repair, persistence of prolapse symptoms, or Xenform or procedure-related complication.  A 
re-intervention may include surgical or non-surgical treatments and can occur for a medical 
complication or for prolapse recurrence. For the purpose of this study surgical interventions 
shall be classified as “re-surgery” and non-surgical interventions shall be classified as “re-
interventions”.  Analyses will be performed to compare the rate of office-based interventions 
and of surgical interventions for medical complications and for prolapse recurrence in both 
treatment groups. 
Non-surgical interventions (re-interventions) are defined as office-based procedures and do 
not involve an operating room procedure.  Examples of non-surgical interventions may 
include but are not limited to an office visit to trim exposed Xenform or suture in the vagina, 
a pessary, or physical therapy to treat procedural complications or persistent prolapse 
symptoms.  Data on non-surgical interventions will be captured in the CRFs.  Subjects will 
continue to be followed per the regular study visit schedule.   
Surgical interventions (re-surgery) are surgical operations performed to correct recurring 
prolapse symptoms, a procedural complication, or Xenform-related complication.  These 
surgical events typically may occur on an outpatient basis yet can require admission to a 
hospital.  The decision to perform a re-surgery for failed prolapse repair or persistence of 
prolapse symptoms will be per physician and subject discretion and all re-surgery data will 
be captured in the Case Report Forms.  All subjects defined as having a prolapse recurrence 
will be those who have anatomic and symptomatic failure of their prolapse surgery (prolapse 
beyond the hymen and symptoms of vaginal bulge).   
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Subjects undergoing a re-surgery will be followed to 36 months post their initial study 
procedure as indicated in Table 11.1-2.  The subject should return to the clinic for the next 
regular study visit as per her original schedule.  If the subject elects to not undergo re-
surgery, then the subject will be followed to the Month 36 visit unless the subject chooses to 
withdraw consent from the study.  No subject will be followed for more than 36 months 
beyond their initial study procedure.  
11.6. Subject Death 
If any serious adverse event results in death (regardless of relatedness to the study device, 
procedure, or pelvic floor), the event is to be documented in the source documentation, Case 
Report Form, and reported to the Sponsor within the timeframe noted in Table 21.6-1 
(Investigator Reporting Requirements).  If an autopsy is conducted, a copy of the final 
autopsy report should be submitted to the Sponsor or designee.  The primary objective of the 
autopsy is to determine the cause of death, complications and other relevant findings.  
12. Statistical Considerations 
12.1. Endpoints 
12.1.1. Primary Endpoint 
The primary endpoint is an assessment of improvement in pelvic organ prolapse severity at 
36 months as compared to Baseline. 
12.1.1.1. Hypotheses  
Non-inferiority testing for effectiveness will be performed for the primary hypothesis.    
Statistical testing will be performed to determine if composite endpoint of anatomic and 
symptomatic success rate in transvaginal biologic mesh repair (treatment) group will be non-
inferior to traditional native tissue repair (control) group.  The null hypothesis is that the 
success rate in treatment group is less than or equal to the success rate in control group minus 
margin: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≤− ∆  
 
The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡− 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐> − ∆     
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑛𝑛𝑛𝑛  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the probability of success in the treatment group and 
control group respectively, and ∆ >0 is defined as the non-inferiority margin. 
Statistical testing will be performed to determine if the overall complication rate (i.e., serious 
device-related or serious procedure-related adverse events) of treatment group is non-inferior 
to the control group.  The null hypothesis is that the complication rate in treatment group is 
greater than or equal to the rate in control group plus margin: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≥∆   
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The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < ∆   
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the overall complication rate in treatment group and 
control group respectively, and ∆ >0 is defined as the non-inferiority margin. 
12.1.1.2. Sample Size  
The statistical power calculation is based on a non-inferiority assumption with a binary 
primary outcome. Objective success, based on a composite endpoint of anatomic and 
symptomatic success at 36 month is assumed to be 70.0%5-8, 16 for the native tissue arm.  
With type I error of 0.05 and type II error of 0.20 (power 80%), 362 subjects (181 subjects 
per arm) are needed to detect non-inferiority of transvaginal biologic to native tissue repair, 
using a margin of 12.0%.   
To assess for safety, the overall complication rate (i.e., serious device-related or serious 
procedure-related adverse events) is anticipated to be approximately 14% per arm.9 With 
type I error of 0.05 and type II error of 0.10 (power 90%), 308 subjects (154 subjects per 
arm) are needed to detect non-inferiority with a margin of 11.6%.  
To assess for office-based interventions for complications, the rate is anticipated to be 
approximately 2%.9 With type I error of 0.025 and type II error of 0.10 (power 90%), 330 
subjects (165 subjects per arm) are needed to detect non-inferiority with a margin of 5%.   
To assess for of surgical intervention for complications, the rate is anticipated to be 
approximately 1%.9 With type I error of 0.025 and type II error of 0.10 (power 90%), 260 
subjects (130 subjects per arm) are needed to detect non-inferiority with a margin of 4%.   
Non-surgical subjects will not be enrolled into this clinical study as all data on this cohort of 
subjects will be obtained from the AUGS Pelvic Floor Disorders Registry under Level 2 and 
analyzed with data from this clinical study.   
Using the above calculations and assuming a 20% loss to follow-up rate, a total of 454 
subjects (227 per study arm) will be enrolled to achieve the primary endpoint of success at 36 
months.   
12.1.1.3. 
Statistical Methods 
For the primary effectiveness endpoint, non-inferiority will be evaluated using a two-sided 
90% confidence interval for the treatment difference (Xenform minus native tissue repair).  If 
the entire confidence interval is above the margin (i.e., –12%), non-inferiority will be 
demonstrated.  The confidence interval will be calculated based on the pooling of treatment 
differences across propensity score strata for a binary endpoint, as described in Section 
12.2.3 (Propensity Score Methodology). 
If any data on the primary efficacy endpoint is missing, multiple imputation will be 
performed in which the missing values will be imputed five times under a logistic 
distribution model, using a fully conditional specification that includes the treatment arm and 
the assessments of the treatment success endpoint at each of 2, 6, 12, 18, and 24 months.  As 
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a sensitivity analysis, the comparison of treatments will also be performed using the 
following methods: 
• Tipping point analysis 
• Available cases only (i.e., only the subjects for whom the endpoint was assessed) 
For the primary safety endpoint, the proportions will be calculated using for the numerator 
the number of subjects with an endpoint event and for the denominator the number of 
subjects in the analysis population (ITT and Per Protocol group).  Non-inferiority will be 
evaluated using a two-sided 90% confidence interval for the treatment difference (Xenform 
minus native tissue repair).  If the entire confidence interval is below the margin (i.e., 
11.6%), non-inferiority will be demonstrated.  The confidence interval will be calculated 
based on the pooling of treatment differences across propensity score strata for a binary 
endpoint, as described in Section 12.2.3 (Propensity Score Methodology). 
12.1.2. Secondary Endpoints 
Secondary endpoints will be to evaluate Xenform-related complications and subject reported 
outcomes as safety endpoints between baseline and 36 months:  
1. Incidence of Xenform erosion 
2. Incidence of Xenform exposure 
3. Incidence of de novo dyspareunia 
4. Improvement in subject specific outcomes at 36 months compared to Baseline (pelvic 
floor symptoms (PFDI-20), QOL (PFIQ-7), sexual functioning (PISQ-12), TOMUS 
pain scale) 
5. Assessment of subject’s level of improvement, measured by the Patient Global 
Impression of Improvement for Prolapse (PGI-I for Prolapse) 
6. Absence of re-intervention or re-surgery for recurrence or persistence of POP or 
Xenform exposure/erosion 
7. Surgical success based on the following composite outcome: 
a. Subjective success:  patient denies symptoms of vaginal bulging per PFDI-20 
question 3, answering “no” or “yes” but “Not at all” bothersome (<2) 
b. Anatomic success (in the operated compartment): 
• Anterior Segment:  No anterior prolapse at or beyond the hymen or 
POP-Q point Ba<0 
• Apical Segment:  The vaginal apex does not descend more than one-
half into the vaginal canal (i.e. POP-Q point C < 1/2 TVL) for multi-
compartment prolapse or POP-Q point C ˂ 0 for single compartment 
apical prolapse. 
c. No retreatment for POP (treated segment):  No additional surgical treatment 
for POP in the segment(s) of the vagina treated at the index surgery or no 
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pessary use since index surgery (‘treated segment’ refers to the target 
compartments in this study, which are the anterior and apical compartments) 
8. Device or procedure related incidence of the following:  pelvic pain, infection, 
vaginal shortening, atypical vaginal discharge, neuromuscular problems, vaginal 
scarring, de novo vaginal bleeding, fistula formation and/or de novo voiding 
dysfunction 
Definitions for the above listed adverse events are included in Section 21.2 (Definitions and 
Classifications).  Rates of incidence for the adverse events will be stratified by primary or 
recurrent prolapse in both treatment groups.   
12.1.2.1. 
Hypotheses 
Statistical testing will be performed to determine if the de novo dyspareunia rate of treatment 
group is non-inferior to the control group. The null hypothesis is that the de novo 
dyspareunia rate in treatment group is greater than or equal to the rate in control group plus 
margin: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≥∆   
The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < ∆   
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the de novo dyspareunia rate in treatment group and 
control group respectively, and ∆ >0 is defined as the non-inferiority margin. 
Statistical testing will be performed to determine if the AE incidences (pelvic pain, infection, 
vaginal shortening, atypical vaginal discharge, neuromuscular problems, vaginal scarring, de 
novo vaginal bleeding, fistula formation and/or de novo voiding dysfunction) rate of 
treatment group is non-inferior to the control group. The null hypothesis is that the AE 
incidences rate in treatment group is greater than or equal to the rate in control group plus 
margin: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≥∆   
The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < ∆   
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the AE incidence rates in treatment group and control 
group respectively, and ∆ >0 is defined as the non-inferiority margin. 
The propensity score adjusted confidence intervals described in Section 12.2.3 (Propensity 
Score Methodology) will be used to summarize the mean score improvement of Quality of 
Life (PFIQ, PFDI, PISQ, TOMUS pain scale) of the Xenform (treatment) group compared to 
that of the native tissue repair (control) group. 
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12.1.2.2. 
Sample Size  
The rate of de novo dyspareunia is anticipated to be approximately 9%.17 With type I error of 
0.05 and type II error of 0.20 (power 80%), 326 subjects (163 subjects per arm) are needed to 
detect non-inferiority with a margin of 7.9%.   
The rate of AE incidence (pelvic pain, infection, vaginal shortening, atypical vaginal 
discharge, neuromuscular problems, vaginal scarring, de novo vaginal bleeding, fistula 
formation and/or de novo voiding dysfunction) is anticipated to be approximately 12%.15-18 
With type I error of 0.05 and type II error of 0.20 (power 80%), 330 subjects (165 subjects 
per arm) are needed to detect non-inferiority with a margin of 8.9%.  
12.1.2.3. 
Statistical Methods 
A comparison of data for all subjects will be included per the following statistical analyses to 
measure for secondary endpoints: 
• Rate of adverse device or procedure related events within 6, 12, 18, 24 and 36 months 
• Overall rate of adverse device or procedure related events within 6, 12, 18, 24, 36 
months 
• Comparison of adverse device or procedure related events between treatment groups 
• Rate and severity of Xenform exposure and erosion within 6, 12, 18, 24, 36 months 
• Assessment of rate of adverse device or procedure related events in subjects with 
reoperation for failed prolapse repair 
• Assessment of rates of/times to reoperation 
• Comparison of rate of adverse device or procedure related events in subjects with re-
surgery in both treatment groups 
• Assessment and comparison between groups of analgesic intake and pain scoring at 
post-operative 6 weeks, 12, 18, 24, 36 months.  Pain score improvement will be 
analyzed with a paired t-test for each group on all patients and with the propensity 
score adjusted confidence intervals for the pain score differences between groups.  
Change in analgesic intake from baseline will be analyzed by McNemar’s test for 
each group on all patients. 
• Assessment of severe blood loss during surgical procedure 
• Duration of surgery from operative report 
• Assessment of re-treatment interventions (i.e. surgery, office-procedure, etc.) 
• Assessment of days to discharge and return to normal activity 
• Assessment of risk factors, including menopausal status, estrogen use, age smoking, 
diagnosis of diabetes, body mass index, concomitant procedures, surgeon training and 
experience  
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A comparison of data between baseline and 36 months for all subjects will be included per 
the following statistical analyses to measure for secondary endpoints: 
• Quality of Life Assessments (PFIQ, PFDI, PISQ, TOMUS) at 6, 12, 18, 24, 36 
months as compared to baseline: paired t-test will be used to compare mean QOL 
score improvement from baseline to 6, 12, 18, 24 and 36 months for each group. 
• Comparison of Quality of Life Assessments improvements between treatment groups 
• Assessment of Quality of Life in subjects with re-surgery after re-surgery 
• Assessment of subject satisfaction at 6, 12, 18, 24, 36 months (PGI-I for Prolapse) 
Propensity score adjusted confidence intervals described in Section 12.2.3 (Propensity Score 
Methodology) will be used to evaluate continuous variables including QOL score 
improvements between two groups.  
12.2. General Statistical Methods 
12.2.1. Analysis Sets 
The Intent-to-Treat (ITT) subject population includes all subjects who provide written 
informed consent to be enrolled into the study and have a surgery initiated (i.e. incision in 
vagina) regardless of their adherence with the entry criteria, regardless of treatment and 
withdrawal/protocol deviations. 
The treated population includes all subjects who undergo a study surgical procedure.  The 
subject is defined to have successfully completed the surgical procedure (i.e. prolapse repair 
successful) and discharged. 
The Per Protocol (PP) population includes all subjects in the ITT Population who received 
the assigned treatment and had no major protocol deviations.  
All primary and secondary endpoints will be analyzed on the ITT Population.  The primary 
safety endpoint and non-safety endpoints will also be analyzed on the per-protocol 
population. 
12.2.2. Control of Systematic Error/Bias 
To reduce selection bias in this non-randomized study, each study center will be permitted to 
enroll subjects in only one of the treatment groups.  Physicians will be selected based on 
device and clinical research experience and the decision as to which device to implant in 
subjects prior to study initiation at each center.  Some study centers may be permitted per 
Boston Scientific to enroll subjects in both treatment and control groups.  All decisions will 
be documented prior to subject enrollment.  All subjects meeting the eligibility criteria at the 
study center will be screened and enrolled as applicable. 
Propensity score stratification will be utilized to address the potential imbalance in risk 
factors between groups, described in Section 12.2.3 (Propensity Score Methodology).  This 
analysis will be performed blind to all clinical outcome data and prior to performing any 
analysis of endpoints. 
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12.2.3. Propensity Score Methodology 
Analyses comparing the treatment groups will be adjusted for the propensity score.  The 
propensity score is the probability that the subject enrolled in the mesh arm rather than the 
native tissue (control) arm, given the characteristics of the subject and center. The 
characteristics identified are as follows: age, race, body mass index, smoking, diabetes, post-
menopausal, prior prolapse repair, prior hysterectomy, estrogen use, POP-Q C measurement, 
POP-Q Ba measurement, POP-Q Bp measurement, concomitant repair for stress urinary 
incontinence, and surgeon case volume.  Logistic regression of both treatment arms (i.e., 
(transvaginal biologic mesh repair vs. native tissue repair) on these characteristics will be 
used to estimate the propensity score.  The subjects will then be partitioned into five strata 
corresponding to quintiles of the propensity score.  If the balance between treatment arms 
within the strata is deemed adequate, the treatment difference adjusted for propensity score 
stratum will be estimated as described in the following. 
The propensity adjusted treatment difference will be based on averaging the treatment 
differences of the propensity score strata.  For a binary outcome, the within-stratum treatment 
difference is 𝐷𝐷𝑗𝑗= 𝑝𝑝𝑇𝑇𝑗𝑗−𝑝𝑝𝐶𝐶𝑗𝑗, where 𝑝𝑝𝑇𝑇𝑗𝑗 and 𝑝𝑝𝐶𝐶𝑗𝑗 is the proportion of treatment and control 
subjects, respectively, in stratum j. The variance of 𝐷𝐷𝑗𝑗 is approximately 
𝑉𝑉𝑗𝑗=
𝑝𝑝𝑇𝑇𝑗𝑗(1 −𝑝𝑝𝑇𝑇𝑗𝑗)
𝑛𝑛𝑇𝑇𝑗𝑗
+
𝑝𝑝𝐶𝐶𝑗𝑗(1 −𝑝𝑝𝐶𝐶𝑗𝑗)
𝑛𝑛𝐶𝐶𝑗𝑗
 
Denoting the number of subjects in stratum j by 𝑛𝑛𝑗𝑗= 𝑛𝑛𝑇𝑇𝑗𝑗+ 𝑛𝑛𝐶𝐶𝑗𝑗 , the treatment difference 
will be estimated by the (weighted) mean of the within-stratum treatment differences 
𝐷𝐷= ෍𝑛𝑛𝑗𝑗
𝑛𝑛𝐷𝐷𝑗𝑗
𝑗𝑗
 
where 𝑛𝑛= ∑𝑛𝑛𝑗𝑗
𝑗𝑗
 is the total sample size across all strata and study arms. D is approximately 
normally distributed with variance 
𝑉𝑉= ෍ቀ𝑛𝑛𝑗𝑗
𝑛𝑛ቁ
2
𝑉𝑉𝑗𝑗
𝑗𝑗
 
from which a confidence interval for the true treatment difference will be constructed. For 
each continuous outcome, the confidence interval will be constructed similarly, with D and V 
obtained as above with the treatment difference within each stratum replaced by 𝐷𝐷𝑗𝑗= 𝑋𝑋ത𝑇𝑇𝑗𝑗−
𝑋𝑋ത𝐶𝐶𝑗𝑗 , where 𝑋𝑋ത𝑇𝑇𝑗𝑗 and 𝑋𝑋ത𝐶𝐶𝑗𝑗 , respectively, is the mean of the treatment and control subjects, and  
𝑉𝑉𝑗𝑗=
𝑆𝑆𝑇𝑇
2
𝑗𝑗
𝑛𝑛𝑇𝑇𝑗𝑗
+
𝑆𝑆𝐶𝐶
2
𝑗𝑗
𝑛𝑛𝐶𝐶𝑗𝑗
 
where 𝑆𝑆𝑇𝑇
2
𝑗𝑗 and 𝑆𝑆𝐶𝐶
2
𝑗𝑗 are the variances of the treatment and control subjects in stratum j. 
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12.3. Data Analyses 
Presentation of summary statistics for continuous variables will include N, mean, median, 
standard deviation, minimum, and maximum values for non-missing data.  For categorical 
variables, the number and percentage under each category for non-missing data will be 
presented. 
Additionally, subjects meeting this study’s eligibility criteria under the PFD Registry may be 
included in the analyses plan.  The intention is to utilize a shared control arm from the PFD 
Registry. 
12.3.1. Rate of Office-Based Intervention for Recurrence 
Statistical testing will be performed to determine if the rate of office-based intervention for 
recurrence in the treatment group will be superior to the control group.  The null hypothesis 
is that the rate of office-based intervention for recurrence in treatment group is greater than 
or equal to the rate in control group: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛𝑛 ≥0   
The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < 0   
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 
 and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the office-based intervention rates for recurrence in 
treatment group and control group respectively.  The rejection of null hypothesis indicates 
the superiority of the treatment group over the control group. 
12.3.2. Rate of Surgical Intervention for Recurrence 
Statistical testing will be performed to determine if the rate of surgical intervention for 
recurrence in treatment group will be superior to the control group.  The null hypothesis is 
that the rate of surgical intervention for recurrence in treatment group is greater than or equal 
to the rate in control group:  
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≥0   
The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < 0    
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 
 and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the surgical intervention rates for recurrence in treatment 
group and control group respectively.  The rejection of null hypothesis indicates the 
superiority of the treatment group over the control group. 
The propensity score adjusted analysis described in Section 12.2.3 (Propensity Score 
Methodology) will be used for testing the null hypothesis and computing the confidence 
intervals for rate of office-based intervention for recurrence and surgical intervention for 
recurrence between treatment group and control group. 
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12.3.3. Rate of Office-Based Intervention for Complications 
Statistical testing will be performed to determine if the rate of office-based intervention for 
complications in the mesh (treatment) group is non-inferior to the native tissue repair 
(control) group.  The null hypothesis is that the rate of office-based intervention for 
complications in treatment group is greater than or equal to the rate in control group plus 
margin: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≥∆   
The alternative hypothesis is:  
 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < ∆   
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the office-based intervention rates for complication in 
treatment group and control group respectively, and ∆ >0 is defined as the non-inferiority 
margin. 
The rate of office-based intervention for complication is anticipated to be approximately 2%.  
With type I error of 0.025 and type II error of 0.10 (power 90%), 330 subjects (165 subjects 
per arm) are needed to detect non-inferiority with a margin of 5%.   
12.3.4. Rate of Surgical Intervention for Complications 
Statistical testing will be performed to determine if the rate of surgical intervention for 
complications of the mesh (treatment) group is non-inferior to the native tissue repair 
(control) group.  The null hypothesis is that the rate of surgical intervention for complications 
in treatment group is greater than or equal to the rate in control group plus margin: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≥∆   
The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < ∆   
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 are the probabilities of having surgical intervention for 
complication in treatment group and control group respectively, and ∆ >0 is defined as the 
non-inferiority margin. 
The rate of surgical intervention complication is anticipated to be approximately 1%.  With 
type I error of 0.025 and type II error of 0.10 (power 90%), 260 subjects (130 subjects per 
arm) are needed to detect non-inferiority with a margin of 4%.   
The propensity score adjusted analysis described in Section 12.2.3 (Propensity Score 
Methodology) will be used for testing the null hypothesis and computing the confidence 
intervals for rate office-based intervention for complication and surgical intervention for 
complication between treatment group and control group. 
For each group, logistic regression will be performed, to include office-based intervention for 
recurrence as a covariate for analyzing the primary endpoint (success rate of improvement in 
pelvic organ prolapse at 36 months) data. 
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For each group, Cox regression will be performed, to include surgical intervention for 
recurrent prolapse as a covariate for analyzing adverse events (pelvic pain, infection, vaginal 
shortening, vaginal scarring, de novo vaginal bleeding, fistula formation and/or de novo 
voiding dysfunction) data. 
Descriptive statistics for the baseline characteristics and QOL outcome for the non-surgery 
(i.e. pessary) group will be summarized from the AUGS PFD Registry Level 1/2 database. 
12.3.5. Sub-Analysis for Sling Repair and Interventions for Recurrence 
12.3.5.1. 
Subjects with only POP repair and those with sling and prolapse repair  
A two sample t-test will be performed in pain score change from baseline to each follow-up 
visit within Xenform or native tissue repair group, to compare groups with and without SUI 
surgery. Using this method of analysis will make it less difficult to assess causality for 
adverse events, including pain. 
12.3.5.2. 
Subjects with office-based intervention for recurrence 
Adverse procedural/device event rates and QOL information will be collected for 36 months, 
regardless of whether or not the subject has office-based intervention for recurrence.    
Event rate for each of device-related or procedure-related adverse events of specified AE 
type (Xenform erosion, Xenform exposure, dyspareunia) during the period after the 
intervention will be summarized by treatment group.  Treatment groups will be compared 
using Cox regression for the event-free survival time (starting at the time of first office based 
intervention) with treatment arm.   
For each QOL instrument, a comparison using t-test will be performed between native tissue 
repair and Xenform group on the basis of QOL score at the first scheduled follow-up after 
office-based intervention for recurrence.  
A two sample t-test will be used to compare groups with office-based intervention for 
recurrence and without intervention within each treatment group.  QOL score change will be 
reported from the last follow-up visit before office-based intervention for recurrence, to the 
next scheduled follow-up visit after office-based intervention for recurrence within each 
treatment group.  For those subjects without recurrence, we will use baseline as the “before” 
time point in analysis, and the QOL data at 6 month follow-up visit as the “after” time point.  
Similarly, event rate for each adverse device and procedure-related event type specified 
(mesh erosion, mesh exposure, dyspareunia), will be compared between subjects with office-
based intervention for recurrence and those without.  This will be done using a Cox 
regression of time to the first onset of each adverse event after the starting time to compare 
groups with office-based intervention for recurrence and within each treatment group.  The 
starting time will be baseline for those subjects without intervention, and time of office-based 
intervention for recurrence for those with intervention. 
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12.3.5.3. Subjects with surgical intervention for recurrence 
The above mentioned analyses for the subgroup with office based intervention for recurrence 
will be repeated for subjects with surgical intervention for recurrence. 
12.3.5.4. Subjects with surgical intervention for recurrence or complications 
Each of device-related or procedure-related adverse events during the period after the re-
surgery will be summarized by the vaginal compartment(s) (i.e. apical only, anterior only, 
apical and anterior) treated in the index procedure within each treatment group. 
12.3.6. Additional Data Analyses 
• Assessment of EQ-5D score for health status at 12, 24 and 36 month as compared to 
baseline 
• Assessment of SSQ-8 score for surgical satisfaction at 6, 12, 24 and 36 month  
Propensity score adjusted confidence intervals described in Section 12.2.3 (Propensity Score 
Methodology) will be used to summarize EQ-5D and SSQ-8 score improvements between 
two groups. 
12.3.7. Sub-Analysis for Interventions for Complications 
The above sub-analyses in Section 12.3.5 (Sub-Analysis for Sling Repair and Interventions 
for Recurrence) will be repeated for re-surgery for complications or recurrence. 
12.3.8. Interim Analysis 
An interim analysis will be performed at 12 months from the last subject enrolled in the 
study; all subjects will be followed to 36 months for the primary endpoint and final analysis.  
This analysis will consist of the primary and some or all of the secondary endpoints and 
demographics if deemed necessary.   
Descriptive statistics by treatment arm along with the 95% confidence interval for the 
treatment difference will be reported after adjusting for propensity scores1.  The descriptive 
statistics includes mean, standard deviation, n, minimum, and maximum for continuous 
variables and frequency statistics for discrete variables. 
                                                 
1 To support United States Premarket Approval Activities, as agreed to on the Presubmission call held on May 
24, 2017 (Q170382), Boston Scientific will submit descriptive statistics for the submission of the PMA, which 
per reclassification document number 2015-33165, is required to be accepted and filed on or before July 5, 
2018. 
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12.3.8.1. 
Hypotheses2 
The interim analysis hypothesis is that transvaginal biologic mesh repair (treatment) is non-
inferior to traditional native tissue repair (control) in both effectiveness and safety at 12 
months.   
Statistical testing will be performed to evaluate whether transvaginal biologic mesh repair 
(treatment) is non-inferior to native tissue repair with respect to the composite treatment 
success endpoint.  The null hypothesis is that the success rate for Xenform is inferior to that 
of the control at a non-inferiority margin of 12%: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≤ −12% 
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 is the success rate in the treatment and control group, 
respectively.  The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡− 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐> −12%     
The rejection of null hypothesis indicates the non-inferiority of transvaginal biologic mesh 
repair. 
If non-inferiority is demonstrated, then the superiority of transvaginal biologic mesh repair at 
12 months will be evaluated, for which the hypotheses are: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡≤𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚> 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐  
The rejection of null hypothesis indicates the superiority of transvaginal biologic mesh 
repair. 
Statistical testing will be performed to determine if the serious complication rate (i.e. serious 
adverse device effects and serious procedure-related adverse events) of the treatment group is 
non-inferior to the control group at 12 months. The null hypothesis is that the serious 
complication rate in treatment group is greater than or equal to the rate in control group plus 
margin of 10%: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 ≥10%  
where 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡  and 𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 is the serious complication rate in the treatment group and 
control group, respectively. The alternative hypothesis is: 
𝐻𝐻𝐻𝐻: 𝜋𝜋𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡−𝜋𝜋𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 < 10%   
12.3.8.2. 
Statistical Methods 
The comparisons of transvaginal biologic mesh repair to native tissue repair will be based on 
a two-sided 90% confidence interval for the treatment difference.  The confidence interval 
will be calculated based on the pooling of treatment differences across propensity score strata 
for a binary endpoint, as described in Section 12.2.3 (Propensity Score Methodology). 
                                                 
2 To support the continued review of the Premarket Approval Application for the United States, Boston 
Scientific will submit hypothesis testing as an Amendment to the initial PMA following acceptance and filing. 
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Missing 12 month data for the composite efficacy endpoint will be handled by multiple 
imputation under a logistic regression model using a fully conditional specification.  The 
imputation model will include treatment group and primary efficacy outcome at 2 and 6 
month.  A total of 5 imputed data sets will be generated. 
The following methods will also be used as sensitivity analyses: 
• Tipping point analysis 
• Observed data only 
 
12.3.9. Justification of Pooling 
The analyses will be presented using pooled data across institutions. For each group, an 
analysis of the poolability will be made using logistic regression for binary outcomes, or 
analysis of variance for continuous outcomes, to assess differences between study institutions 
and to justify pooling data across institutions.  Centers with less than 5 ITT patients may be 
combined.  
12.3.10. Multivariable Analyses 
For each treatment group, univariate and multivariate analyses will be performed to assess 
possible predictors of the improvement in pelvic organ prolapse at 36 month, mesh-related 
complications and subject reported outcomes.  Possible predictors may include, but not 
limited to, demographic/baseline data and risk factors data.  Factors from the univariate 
model with p≤0.20 will also be put into multivariate model using a stepwise procedure in a 
logistic regression model.  The significance thresholds for entry and exit into the model will 
be set to p<0.10.  Analysis of Covariance (ANCOVA) will be performed for subject reported 
outcome with appropriate predictors.  
13. Data Management 
13.1. Data Collection, Processing, and Review 
Good Clinical Practice Guidelines require that investigators maintain information (i.e., 
Source Data) in the subject’s medical records, laboratory reports, clinic charts, etc. (i.e., 
Source Documents) that corresponds to data recorded on the Case Report Forms.  In order to 
comply with these requirements, the following information should be maintained as source 
documentation, including but not limited to: 
• Medical history/physical condition of the subject before enrollment 
• Protocol entry criteria 
• Dated and signed notes for specific results of procedures and exams 
• Laboratory reports 
• Information related to adverse device effects 
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• Surgical notes, including subject condition and re-surgery if applicable 
• Quality of life assessments and TOMUS pain scales 
• Discharge Summaries/Procedure reports 
• Autopsy reports 
Subject data will be recorded on Case Report Forms which will be provided by Boston 
Scientific or designated vendor.  The Source Data reported on the Case Report Forms shall 
be derived from source documentation and shall be consistent with these source documents.  
Any discrepancies shall be explained and documented.  Any change or correction made to 
the clinical data will be dated, initialed, and explained, if necessary, and shall not obscure the 
original entry.  An audit trail shall be maintained which will be made available for review by 
Boston Scientific or its representative.  Any queries to the data will be addressed by the study 
center staff in a timely manner.  
13.2. Data Retention 
The investigator will maintain, at the investigative site, in original format all essential study 
documents and source documentation that support the data collected on study subjects in 
compliance with ISO 14155:2011 (Clinical investigation of medical devices for human 
subjects - Good clinical practice).  Documents must be retained for at least 2 years after the 
last approval of a marketing application or until at least 2 years have elapsed since the formal 
discontinuation of the clinical investigation of the product.  These documents will be retained 
for a longer period of time by agreement with Boston Scientific or in compliance with other 
local regulations.  It is Boston Scientific’s responsibility to inform the investigator when 
these documents no longer need to be maintained.  The investigator will take measures to 
ensure that these essential documents are not accidentally damaged or destroyed.  If for any 
reason the investigator withdraws responsibility for maintaining these essential documents, 
custody must be transferred to an individual who will assume responsibility and Boston 
Scientific must receive written notification of this custodial change. 
14. Amendments  
If a protocol revision is necessary for reasons including but not limited to, the rights, safety 
or welfare of the subject, or scientific integrity of the data, an amendment is required. 
Appropriate approvals (e.g., IRB/EC/FDA/CA) of the revised protocol must be obtained 
prior to implementation. 
15. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify 
Boston Scientific and the reviewing IRB/EC of any deviation from the investigational plan to 
protect the life or physical well-being of a subject in an emergency, and those deviations 
which affect the scientific integrity of the clinical investigation. Such notice shall be given as 
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soon as possible, but no later than 5 working days after the emergency occurred, or per 
prevailing local requirements, if sooner than 5 working days.  
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to Boston Scientific.  Study centers may also 
be required to report deviations to their IRB/EC, per local guidelines and government 
regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including notification, center re-training, or 
discontinuation) will be put into place by Boston Scientific. 
16. Device/Equipment Accountability 
This is a post-market study and therefore no investigational devices are being used.  All 
commercial and institutional policies regarding but not limited to device use, purchase and/or 
storage will be followed.  
17. Compliance 
17.1. Statement of Compliance 
This study will be conducted in accordance with ISO 14155:2011 (Clinical investigation of 
medical devices for human subjects - Good clinical practice), ethical principles that have 
their origins in the Declaration of Helsinki, and pertinent individual country laws and 
regulations.  The study shall not begin until the required approval/favorable opinion from the 
IRB/EC and/or regulatory authority has been obtained, as appropriate.  Any additional 
requirements imposed by the IRB/EC or regulatory authority shall be followed, if 
appropriate. 
17.2. Investigator Responsibilities 
The Principal Investigator of an investigational center is responsible for ensuring that the 
study is conducted in accordance with the Clinical Study Agreement, the investigational 
plan/protocol, ISO 14155:2011 (Clinical investigation of medical devices for human subjects 
- Good clinical practice), ethical principles that have their origins in the Declaration of 
Helsinki, any conditions of approval imposed by the reviewing IRB/EC, and prevailing local 
and/or country laws and/or regulations, whichever affords the greater protection to the 
subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Investigator Agreement and Protocol Signature 
page documenting his/her agreement to conduct the study in accordance with the 
protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the center team through up-to-date 
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curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study 
or interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and 
physical well-being of a subject in an emergency; document and explain any 
deviation from the approved protocol that occurred during the course of the clinical 
investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all 
clinical-investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to 
Boston Scientific in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) 
every adverse event and observed device deficiency. 
• Report to Boston Scientific, per the protocol requirements, all SAEs and device 
deficiencies that could have led to a SADE. 
• Report to the IRB/EC and regulatory authorities any SAEs and device deficiencies 
that could have led to a SADE, if required by the national regulations or this protocol 
or by the IRB/EC, and supply Boston Scientific with any additional requested 
information related to the safety reporting of a particular event. 
• Allow Boston Scientific or its designee to perform monitoring and auditing activities, 
and be accessible to the monitor and respond to questions during monitoring visits. 
• Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with this protocol and local 
IRB/EC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation 
in a clinical study in the case of adverse events, as described in the Informed Consent 
Form (ICF). 
• Inform the subject of the nature and possible cause of any adverse events 
experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together 
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with identification and compliance information for concomitant treatment measures 
(contact address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical 
investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained 
and documented during the clinical investigation. 
• Ensure that maintenance and calibration of the equipment relevant for the assessment 
of the clinical investigation is appropriately performed and documented, where 
applicable. 
17.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, included but not limited to conducting 
the informed consent process, the investigator is responsible for providing appropriate 
training and adequate supervision of those to whom tasks are delegated. The investigator is 
accountable for regulatory violations resulting from failure to adequately supervise the 
conduct of the clinical study.  
17.3. Institutional Review Board/ Ethics Committee 
Prior to gaining Approval-to-Enroll status, the investigational center will provide to the 
sponsor documentation verifying that their IRB/EC is registered or that registration has been 
submitted to the appropriate agency, as applicable according to national/regulatory 
requirements.   
A copy of the written IRB/EC and/or competent authority approval of the protocol (or 
permission to conduct the study) and Informed Consent Form, must be received by the 
sponsor before recruitment of subjects into the.  Prior approval must also be obtained for 
other materials related to subject recruitment or which will be provided to the subject. 
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study 
as required by local/country or IRB/EC requirements.  Copies of the Investigator’s reports 
and the IRB/EC continuance of approval must be provided to Boston Scientific.  
17.4. Sponsor Responsibilities 
All information and data sent to Boston Scientific concerning subjects or their participation 
in this study will be considered confidential by Boston Scientific.  Only authorized Boston 
Scientific personnel or a Boston Scientific representative will have access to these 
confidential records.  Authorized regulatory personnel have the right to inspect and copy all 
records pertinent to this study. Study data collected during this study may be used by Boston 
Scientific for the purposes of this study, publication, and to support future research and/or 
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other business purposes.  All data used in the analysis and reporting of this study will be 
without identifiable reference to specific subject name. 
Boston Scientific will keep subjects’ health information confidential in accordance with all 
applicable laws and regulations.  Boston Scientific may use subjects’ health information to 
conduct this research, as well as for additional purposes, such as overseeing and improving 
the performance of its device, new medical research and proposals for developing new 
medical products or procedures, and other business purposes. Information received during 
the study will not be used to market to subjects; subject names will not be placed on any 
mailing lists or sold to anyone for marketing purposes.  
17.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by Boston 
Scientific for subjects in the study will be obtained. 
18. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the monitor verifies that study records are 
adequately maintained, that data are reported in a satisfactory manner with respect to 
timeliness, adequacy, and accuracy, and that the investigator continues to have sufficient 
staff and facilities to conduct the study safely and effectively. The investigator/institution 
guarantees direct access to original source documents by Boston Scientific personnel, their 
designees, and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by Boston Scientific or its 
designees, as well as inspection by appropriate regulatory authorities.  It is important that the 
investigator and relevant study personnel are available during on-site monitoring visits or 
audits and that sufficient time is devoted to the process. 
19. Potential Risks and Benefits 
19.1. General   
The risks and benefits of performing a transvaginal procedure to treat pelvic organ prolapse 
in the following subjects should be carefully considered due to additional risks associated 
with their conditions: 
• Women planning future pregnancies 
• Overweight women (weight parameters to be determined by the physician) 
• Subjects with blood coagulation disorder 
• Subjects with a compromised immune system or any other condition that would 
compromise healing 
• Subjects with renal insufficiency or upper urinary tract obstruction 
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19.2. Anticipated Adverse Events  
The following anticipated adverse events (AE) have been reported due to transvaginal 
prolapse repair, which includes repairs with the treatment device, but are not limited to: 
• Abscess 
• Adhesion  
• Allergic, Hypersensitivity or Other Immune Reaction 
• Bleeding (including vaginal or perineal) 
• Bruising/Hematoma 
• Dehiscence of vaginal incision 
• Detrusor Instability 
• De Novo Dyspareunia 
• Edema/Erythema 
• Exposure or Extrusion (Rejection) 
• Erosion  
• Fistula 
• Foreign Body Reaction 
• Granulation Tissue Formation 
• Hemorrhage 
• Incontinence (including fecal) 
• Infection 
• Inflammation (acute or chronic) 
• Irritation 
• Necrosis 
• Neuromuscular Events (including groin and leg pain) 
• Organ perforation 
• Overactive bladder 
• Pain 
• Recurrence 
• Resurgery 
• Urinary Retention 
• Urinary Tract Obstruction 
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• Vessel/Nerve Injury 
• Vaginal Discharge (e.g. atypical) 
• Vaginal Shortening or Stenosis 
• Sexual Dysfunction 
19.2.1. Xenform Exposure and Erosion Event Classification 
Assessment of Xenform exposure and/or erosion will occur at all follow-up visits with pelvic 
examinations performed at 2, 6, 12, 18, 24, and 36 Months post-procedure.  Identification of 
Xenform exposure and/or erosion will occur by the medical staff member performing the 
pelvic exam and will be documented as an adverse event on the Case Report Forms.   
19.3. Risks Associated with Participation in the Clinical Study 
There are no additional risks with participation in this clinical study outside of the anticipated 
risks (see Section 19.2) for pelvic organ prolapse as conducted according to standard of care 
procedures.   
19.4. Risk Minimization Actions 
Additional risks may exist.  Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying Boston Scientific with all pertinent 
information required by this protocol. 
19.5. Anticipated Benefits 
Theoretical benefits of transvaginally placed Xenform for the treatment of pelvic organ 
prolapse may include reduction in POP symptoms.  
19.6. Risk to Benefit Rationale 
The use of transvaginally placed mesh has been shown to reduce recurrent prolapse 
following pelvic floor repair. There have been many randomized controlled trials comparing 
outcomes for pelvic floor repair procedures using mesh to non-mesh repair. Of those studies, 
a reduced incidence of recurrent prolapse in the mesh-procedure group has been reported as 
compared to non-mesh groups.   
However, the risk of mesh-related complications has been reported and can be linked to risk 
factors including body mass index (BMI), concomitant hysterectomy, and physician 
experience.  There is no new literature to indicate there would be an unsatisfactory risk 
benefit profile for the use of transvaginally placed mesh for the treatment of POP.   
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20. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
all subjects or their legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to performing any study-required 
procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155:2011 (Clinical investigation of medical 
devices for human subjects - Good clinical practice), any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority body, as applicable.  The ICF must be 
accepted by Boston Scientific or its designee (e.g., CRO), and approved by the center’s 
IRB/EC, or central IRB, if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study.  The ICF template may be modified to meet the requirements of 
the investigative center’s IRB/EC.  Any modification requires approval from Boston 
Scientific or its designee (e.g., CRO) prior to use of the form.  The ICF must be in a language 
understandable to the subject and if needed, BSC will assist the center in obtaining a written 
consent translation.  Translated consent forms must also have IRB/EC approval prior to their 
use.  Privacy language shall be included in the body of the form or as a separate form as 
applicable.   
The process of obtaining Informed Consent shall: 
• be conducted by the Principal Investigator or designee authorized to conduct the 
process,  
• include a description of all aspects of the clinical study that are relevant to the 
subject’s decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects 
throughout the clinical study. 
The ICF shall always be signed and personally dated by the subject or legal representative 
and by the investigator or an authorized designee responsible for conducting the informed 
consent process.  If a legal representative signs, the subject shall be asked to provide 
informed consent for continued participation as soon as his/her medical condition allows.  
The original signed ICF will be retained by the center and a copy of the signed and dated 
document and any other written information must be given to the person signing the form.  
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Failure to obtain subject consent will be reported by BSC to the applicable regulatory body 
according to their requirements (e.g., FDA requirement is within 5 working days of learning 
of such an event).  Any violations of the informed consent process must be reported as 
deviations to the sponsor and local regulatory authorities (e.g. IRB/EC), as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF.  In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the protocol, a change in Principal Investigator, administrative changes, or following 
annual review by the IRB/EC.  The new version of the ICF must be approved by the IRB/EC. 
Boston Scientific approval is required if changes to the revised ICF are requested by the 
center’s IRB/EC.  The IRB/EC will determine the subject population to be re-consented. 
A Screening/Enrollment Log will be maintained to document select information about 
candidates who fail to meet the general or “other specific” entry criteria.  
21. Safety Reporting 
21.1. Reportable Events by Investigational Site to Boston Scientific 
Any device-related, procedure-related, or pelvic floor-related adverse event experienced by 
the study subject after informed consent and once considered enrolled in the study, whether 
during or subsequent to the procedure, must be recorded in the CRF. 
Refer to Section 19 (Potential Risks and Benefits) for the known risks associated with the 
study device(s). 
Definitions of the adverse events included in the secondary endpoint will match the 
definitions created for the AUGS PFD Registry.  All event definitions will be provided to the 
sites as part of a dictionary in the Manual of Operations. 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency.  
Underlying diseases are not reported as AEs unless there is an increase in severity or 
frequency during the course of the investigation.  Death should not be recorded as an AE, but 
should only be reflected as an outcome of a specific SAE (see Section 21.2 for AE 
definitions).  
21.2. Definitions and Classification 
Adverse event definitions are provided in Table 21.2-1.  Administrative edits were made to 
combine definitions from ISO 14155:2011 (Clinical investigation of medical devices for 
human subjects - Good clinical practice) and MEDDEV 2.7/3 12/2010. 
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Table 21.2-1: Adverse Event Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155:2011 
Ref: MEDDEV 2.7/3 12/2010 
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the investigational 
medical device.  
NOTE 1:  This includes events related to the investigational medical device 
or comparator. 
NOTE 2:  This definition includes events related to the procedures involved 
(any procedure in the clinical investigation plan). 
NOTE 3:  For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Serious Adverse Event (SAE) 
 
Ref: ISO 14155:2011 
Ref: MEDDEV 2.7/3 12/2010 
Adverse event that: 
• Led to death, 
• Led to serious deterioration in the health of the subject, that either 
resulted in: 
- 
a life-threatening illness or injury, or 
- 
a permanent impairment of a body structure or a body function, or 
- 
in-patient  or prolonged hospitalization of existing hospitalization, 
or 
- 
medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
• Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
NOTE:  Planned hospitalization for a pre-existing condition, or a procedure 
required by the clinical investigational plan, without serious deterioration in 
health, is not considered a serious adverse event.  
Device Deficiency 
 
Ref: ISO 14155:2011 
Ref: MEDDEV 2.7/3 12/2010 
A device deficiency is any inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety or performance. 
NOTE:  Device deficiencies include malfunctions, misuse or use errors, and 
inadequate labeling. 
Abbreviations: EC=Ethics Committee; IRB=Institutional Review Board 
 
21.3. Relationship to Study Device (Xenform Cohort Only) 
The investigator must assess the relationship of the AE to the study device as related or 
unrelated.  See criteria in Table 21.3-1: 
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Table 21.3-1: Criteria for Assessing Relationship of Study Device to Adverse Event 
Classification 
Description 
Unrelated  
(Not Related) 
• 
The adverse event is determined to be due to a concurrent illness or effect of 
another device/drug and is not related to the investigational product. 
Related  
(Possible, Probable 
or Definite) 
• 
The adverse event is determined to be potentially related to the investigational 
product, and an alternative etiology is equally or less likely compared to the 
potential relationship to investigational product, or 
• 
There is a strong relationship to investigational product, or recurs on re-
challenge, and another etiology is unlikely, or 
• 
There is no other reasonable medical explanation for the event. 
 
21.4. Relationship to Study Procedure 
The investigator must assess the relationship of the AE to the study procedure as unrelated, 
possibly related, probably related, or definitely related. See criteria in Table 21.4-1. 
Table 21.4-1: Criteria for Assessing Relationship to Study Procedure 
Classification 
Description 
Unrelated  
(Not Related) 
• 
No evidence that the timing of the adverse event has a relationship to the study 
procedure performed. 
Possibly Related 
• 
The adverse event has a timely relationship to the study procedure performed.  
However, a potential alternative etiology may be responsible for the adverse 
event. 
Probably Related 
• 
The adverse event has a timely relationship to the study procedure performed and 
the causative relationship can be clearly established. No potential alternative 
etiology is apparent.  
Definitely Related 
• 
The adverse event has a timely relationship to the study procedure performed and 
the causative relationship can be clearly established. No potential alternative 
etiology is apparent. 
• 
There is no other reasonable medical explanation for the event. 
 
21.5. Relationship to Pelvic Floor 
The investigator must assess the relationship of the AE to the pelvic floor as unrelated or 
related.  See criteria in Table 21.5-1. 
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Table 21.5-1: Criteria for Assessing Relationship to Pelvic Floor 
Classification 
Description 
Unrelated  
• 
No evidence that the adverse event has a relationship to the pelvic floor and 
supporting tissues. 
Related 
 
• 
The adverse event is determined to be potentially related to the pelvic floor and 
supporting tissues including but not limited to lacerations, avulsions, tears, pelvic 
organ prolapse (cystocele, rectocele, enterocele, uterine, rectal), urinary 
incontinence (stress, urge), urinary voiding dysfunction (retention, obstructed 
voiding, incomplete emptying), fecal incontinence (urgency, irritable bowel 
syndrome), defecatory dysfunction (constipation, obstipation, stool trapping, 
IBS), pain (dyspareunia, pelvic, perineal), and infection (bladder, urinary tract, 
vaginal). 
• 
There is a strong relationship to the pelvic floor and supporting tissues, and 
another etiology is unlikely, or 
• 
There is no other reasonable medical explanation for the event. 
 
21.6. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 21.6-1. 
Table 21.6-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline  
Serious Adverse Events related to the 
study device, procedure and/or pelvic 
floor or events resulting in death 
regardless of relationship to the 
device, procedure or pelvic floor. 
Complete AE CRF page with 
all available new and updated 
information. 
 
• Within 2 business days of first 
becoming aware of the event 
or as per local/regional 
regulations. 
• Reporting required through the 
end of the study. 
If requested by Sponsor 
provide all relevant source 
documentation (unidentified) 
for the reported event. 
• When documentation is 
available 
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Table 21.6-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline  
Adverse Events related to the study 
device and/or procedure. 
Events assessed for reporting shall 
include but are not limited to: 
• 
Pelvic pain 
• 
Infection (by type) 
• 
De novo dyspareunia 
• 
Vaginal shortening 
• 
Vaginal scarring 
• 
De novo vaginal bleeding 
• 
Atypical vaginal discharge 
• 
Fistula formation 
• 
De novo voiding dysfunction 
(including de novo 
incontinence) 
• 
Neuromuscular problems 
(including groin and leg pain) 
• 
Revision/re-surgery 
• 
Recurrent prolapse 
• 
Xenform exposure 
• 
Xenform erosion 
Complete the AE CRF page, 
which contains such 
information as onset date of 
the AE, treatment provided if 
any, resolution, assessment of 
seriousness, and relationship to 
study device. 
• In a timely manner (e.g., 
recommended within 10 
business days of first 
becoming aware of the event). 
• Reporting required through 
end of subject participation. 
Adverse Events related to the pelvic 
floor.  
Events assessed for reporting shall 
include but are not limited to: 
• 
Urinary tract infections 
• 
Pelvic organ prolapse 
• 
Urinary incontinence 
• 
Fecal incontinence 
• 
Bladder, urinary tract, or 
vaginal infections 
• 
Pelvic Pain 
Complete the AE CRF page, 
which contains such 
information as onset date of 
the AE, treatment provided if 
any, resolution, assessment of 
seriousness, and relationship to 
study device. 
• In a timely manner (e.g., 
recommended within 10 
business days of first 
becoming aware of the event). 
• Reporting required through 
end of subject participation. 
Device Deficiencies (including but 
not limited to failures, malfunctions, 
and product nonconformities). 
NOTE:  Any Investigational Device 
Deficiency that might have led to a 
serious adverse event if a) suitable 
action had not been taken or b) 
intervention had not been made or c) 
if circumstances had been less 
fortunate is considered a reportable 
event. 
Complete CRF with all 
available new and updated 
information. 
• Within 1 business day of first 
becoming aware of the event. 
• Reporting required through the 
end of the study. 
Abbreviations: AE=adverse event; CRF=case report form 
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21.7. Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to complications, malfunctions, use errors, 
product nonconformities, and labeling errors) will be documented and reported to Boston 
Scientific.  If possible, the device(s) should be returned to BSC for analysis. Instructions for 
returning the device(s) will be provided.  If it is not possible to return the device, the 
investigator should document why the device was not returned and the final disposition of the 
device.  Device failures and malfunctions should also be documented in the subject’s medical 
record. 
Device deficiencies (including but not limited to failures, malfunctions, and product 
nonconformities) are not to be reported as adverse events.  However, if there is an adverse 
event that results from a device failure or malfunction, that specific event would be recorded 
on the appropriate CRF. 
Any Device Deficiency that might have led to a serious adverse event if a) suitable action 
had not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate is considered a reportable event. 
21.8. Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
Boston Scientific is responsible for reporting adverse event information to all participating 
investigators and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IRB/EC, and regulatory 
authorities of an SAE as required by local/regional regulations. 
22. Committees 
22.1. Safety Monitoring Process 
To promote early detection of safety issues, an internal Safety Monitoring Team will provide 
evaluations of safety events.  Success of this program requires dynamic collection of 
unmonitored data as soon as the event is reported.  This is expedited through Boston 
Scientific’s Safety Office, which is responsible for coordinating the collection of information 
for the subject dossier from the centers.  During regularly scheduled monitoring visits, 
clinical research monitors will support the dynamic reporting process through their review of 
source document information. 
23. Suspension or Termination 
23.1. Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or administrative reasons and reasons related to protection 
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of subjects.  Investigators, associated IRBs/ECs, and regulatory authorities, as applicable, 
will be notified in writing in the event of study termination. 
23.1.1. Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following. 
• The occurrence of safety events that present a significant or unreasonable risk to 
subjects enrolled in the study. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue development of 
the device. 
23.2. Termination of Study Participation by the Investigator or Withdrawal of IRB/ EC 
Approval 
Any investigator, or IRB/ EC in the Uphold LITE Study may discontinue participation in the 
study or withdrawal approval of the study, respectively, with suitable written notice to 
Boston Scientific.  Investigators, associated IRBs/ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of these occurrences. 
23.3. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating centers by Boston Scientific. 
The IRB/EC and regulatory authorities, as applicable, will be notified.  Detailed information 
on how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB or EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by Boston Scientific. 
In the event an investigator terminates participation in the study, study responsibility will be 
transferred to a co-investigator, if possible.  In the event there are no opportunities to transfer 
investigator responsibility; detailed information on how enrolled subjects will be managed 
thereafter will be provided by Boston Scientific. 
23.4. Criteria for Suspending/Terminating a Study Center 
Boston Scientific reserves the right to stop the inclusion of subjects at a study center at any 
time after the study initiation visit if no subjects have been enrolled for a period beyond 12 
months after center initiation, or if the center has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of investigator participation, all testing equipment, as applicable, 
will be returned to Boston Scientific unless this action would jeopardize the rights, safety or 
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well-being of the subjects.  The IRB/EC and regulatory authorities, as applicable, should be 
notified.  All subjects enrolled in the study at the center will continue to be followed per 
protocol requirements.  The Principal Investigator at the center must make provision for these 
follow-up visits unless Boston Scientific notifies the investigational center otherwise. 
24. Publication Policy 
In accordance with the Corporate Policy on the Conduct of Human Subject Research, BSC 
requires disclosure of its involvement as a sponsor or financial supporter in any publication 
or presentation relating to a Boston Scientific study or its results.  In accordance with the 
Corporate Policy for the Conduct of Human Subject Research, Boston Scientific will submit 
study results for publication (regardless of study outcome) following the conclusion or 
termination of the study.  Boston Scientific adheres to the Contributorship Criteria set forth 
in the Uniform Requirements of the International Committee of Medical Journal Editors 
(ICMJE; http://www.icmje.org).  In order to ensure the public disclosure of study results in a 
timely manner, while maintaining an unbiased presentation of study outcomes, BSC 
personnel may assist authors and investigators in publication preparation provided the 
following guidelines are followed. 
• All authorship and contributorship requirements as described above must be 
followed. 
• Boston Scientific involvement in the publication preparation and the Boston 
Scientific Publication Policy should be discussed with the Coordinating Principal 
Investigator(s) and/or Executive/Steering Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding 
publication content, review, approval, and submission.  
 
 
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25. References 
1Clark, A.L., Gregory, T., Smith, V.J., and Edwards, R. Epidemiologic evaluation of reoperation for surgically 
treated pelvic organ prolapse and urinary incontinence. American Journal of Obstetrics and Gynecology 2003; 
189, 1261-1267 
2Goldstein, H.B., Maccarone, J., Naughton, M.J., Aguine, O.A., Patel, R.C. A multicenter prospective trial 
evaluating fetal bovine dermal graft (Xenform Matrix) for pelvic reconstructive surgery. BMC Urology 2010, 
10:21 
3Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managed pelvic organ 
prolapse and urinary incontinence. Obstet Gynecol 1997; 89:501¬6 
4Weber AM, Walters MD, Piedmonte MR, Ballard LA. Anterior colporrhaphy: A randomized trial of three 
surgical techniques. Am J Obstet Gynecol 2001;185:1299-1306. 
5Colombo M, Milani R. Sacrospinous ligament fixation and modified McCall culdoplasty during vaginal 
hysterectomy for advanced uterovaginal prolapse. Am J Obstet Gynecol 1998;179:13-20. 
6Maher CF, Qatawneh AM, Dwyer PL, Carey MP, Cornish A, Schluter PJ. Abdominal sacral colpopexy or 
vaginal sacrospinous colpopexy for vaginal vault prolapse: a prospective randomized study. Am J Obstet 
Gynecol 2004;190:20-6. 
7Shull BL, Capen CV, Riggs MW, Kuehl TJ. Preoperative and postoperative analysis of site-specific pelvic 
support defects in 81 women treated with sacrospinous ligament suspension and pelvic reconstruction. Am J 
Obstet Gynecol 1992;166:1764-8. 
8Benson JT, Lucente V, McClellan E. Vaginal versus abdominal reconstructive surgery for the treatment of 
pelvic support defects: A prospective randomized study with long-term outcome evaluation. Am J Obstet 
Gynecol 1996:175:1418-21. 
9Diwadkar GB, Barber MD, Feiner B, Maher C, Jelovsek JE. Complication and Reoperation Rates After Apical 
Vaginal Prolapse Surgical Repair. Ob Gyn 2009:113(2):367-373. 
10Guerette, N., Peterson, T.V., Aguirre, O.A., Vandrie, D.M., Biller, D.H., Davilla, G.W., Anterior repair with 
or without collagen matrix reinforcement; a randomized controlled trial. Obstet. Gynecol 2009: 114, 59-65. 
11Rubin DB. Estimating Causal Effects from Large Data Sets Using Propensity Scores.  Annals of Internal 
Medicine (1997) 127:757-763 
12Rosenbaum PR, Rubin DB.  The Central Role of the Propensity Score in Observational Studies.  Biometrika 
(1983) 70:41-55.   
15Altman DA, et al. Anterior Colporrhaphy versus Transvaginal Mesh for Pelvic-Organ Prolapse. NEJM 2011 
May 12: 364(19):1826-1836. 
16Withagen M., et al. Trocar-Guided Mesh Compared With Conventional Vaginal Repair in Recurrent Prolapse: 
A Randomized Controlled Trial. Ob Gyn 2011 Feb;117(2) Part 1:242-250. 
17Abed H, Rahn DD, Lowenstein L, Balk EM, Clemons JL, Rogers RG.  Incidence and management of graft 
erosion, wound granulation, and dyspareunia following vaginal prolapse repair with graft materials:  as 
systematic review.  Int Urogynecol J (2011) 22:789-798. 
18Vollebregt A., Fischer K., Gietelink D. and Van Der Vaart C.H. BJOG: An International Journal of Obstetrics 
and Gynaecology 2011 118:12 (1518-1527).  
19Chmielewski L, Walters MD, Weber AM, et al. Reanalysis of a randomized trial of 3 techniques of anterior 
colporrhaphy using clinically relevant definitions of success. Am J Obstet Gynecol 2011;205:69.e1-8. 
 
 
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