Novel Web-based, Self-directed Intervention for Chronic Pelvic Pain
Phase: NA
Conditions: Chronic Pelvic Pain, Endometriosis
Sponsor: University of Michigan

Based on the NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
 
Novel web-based, self-directed intervention for 
chronic pelvic pain  
 
IRB approval: 7/16/2024 
Protocol Number: HUM00231526  
National Clinical Trial (NCT) Identified Number: NCT06352840 
 
 
 
 

Based on the NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
 
 
Novel web-based, self-directed intervention for 
chronic pelvic pain  
 
Protocol Number: HUM00231526  
National Clinical Trial (NCT) Identified Number: NCT06352840 
Principal Investigator*: Sara Till, MD, MPH 
Sponsor: University of Michigan 
Grant Title: An intervention for chronic pelvic pain 
Grant Number: 1K23HD09928301A1 
Funded by: NICHD 
Version Number:  v.19 
10 July 2024 
 
 
 
 

Based on the NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the 
NIH terms of award.  
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .............................................................................................................................. 2 
1 
PROTOCOL SUMMARY ............................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................................ 3 
1.2 
Schema ................................................................................................................................................. 4 
1.3 
Schedule of Activities .......................................................................................................................... 5 
2 
INTRODUCTION ............................................................................................................................................ 6 
2.1 
Study Rationale .................................................................................................................................... 6 
2.2 
Background........................................................................................................................................... 6 
2.3 
Risk/Benefit Assessment .................................................................................................................... 7 
2.3.1 
Known Potential Risks ..................................................................................................... 7 
2.3.2 
Known Potential Benefits ................................................................................................ 8 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 8 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 8 
4 
STUDY DESIGN ........................................................................................................................................... 10 
4.1 
Overall Design .................................................................................................................................... 10 
4.2 
Scientific rational for study design ................................................................................................... 11 
5 
STUDY POPULATION ................................................................................................................................ 12 
5.1 
Inclusion Criteria ................................................................................................................................ 12 
5.2 
Exclusion Criteria ............................................................................................................................... 12 
5.3 
Screen Failures .................................................................................................................................. 13 
5.4 
strategies for recruitment and retention .......................................................................................... 13 
5.5 
compensation ..................................................................................................................................... 14 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................ 14 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ...................................... 14 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................. 14 
6.2 
Fidelity ................................................................................................................................................. 14 
6.2.1 
Interventionist Training and Tracking .......................................................................... 15 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 15 
6.4 
Study Intervention/Experimental Manipulation Adherence.......................................................... 15 
6.5 
Concomitant Therapy ........................................................................................................................ 15 
6.5.1 
Rescue Therapy ............................................................................................................. 16 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ......................................................................................... 16 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ............................................. 16 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 16 
7.3 
Lost to Follow-Up ............................................................................................................................... 16 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 17 
8.1 
SCREENING PROCEDURES ......................................................................................................... 17 
8.2 
stUDY EVALUATION AND PROCEDURES ................................................................................. 17 
8.3 
safety assessments ........................................................................................................................... 19 
8.4 
Adverse Events and Serious Adverse Events ............................................................................... 20 
8.4.1 
Definition of Adverse Events ........................................................................................ 20 
8.4.2 
Definition of Serious Adverse Events .......................................................................... 20 
8.4.3 
Classification of an Adverse Event .............................................................................. 20 
8.4.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 22 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
8.4.5 
Adverse Event Reporting .............................................................................................. 22 
8.4.6 
Serious Adverse Event Reporting ............................................................................... 22 
8.4.7 
Reporting Events to Participants ................................................................................. 23 
8.5 
Unanticipated Problems .................................................................................................................... 23 
8.5.1 
Definition of Unanticipated Problems .......................................................................... 23 
8.5.2 
Unanticipated Problems Reporting .............................................................................. 23 
8.5.3 
Reporting Unanticipated Problems to Participants ................................................... 24 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 24 
9.1 
Statistical Hypotheses ....................................................................................................................... 24 
9.2 
Sample Size Determination .............................................................................................................. 24 
9.3 
Populations for Analyses .................................................................................................................. 25 
9.4 
Statistical Analyses............................................................................................................................ 25 
9.4.1 
General Approach .......................................................................................................... 25 
9.4.2 
Analysis of the Primary Endpoint(s) ............................................................................ 25 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 26 
9.4.4 
Safety Analyses .............................................................................................................. 26 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 26 
9.4.6 
Planned Interim Analyses ............................................................................................. 26 
9.4.7 
Sub-Group Analyses ..................................................................................................... 26 
9.4.8 
Tabulation of Individual Participant Data .................................................................... 26 
9.4.9 
Exploratory Analyses ..................................................................................................... 27 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 27 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 27 
10.1.1 
Study Discontinuation and Closure ............................................................................. 27 
10.1.2 
Confidentiality and Privacy ........................................................................................... 28 
10.1.3 
Future Use of Stored Specimens and Data ............................................................... 29 
10.1.4 
Key Roles and Study Governance .............................................................................. 29 
10.1.5 
Safety Oversight ............................................................................................................. 29 
10.1.6 
Clinical Monitoring .......................................................................................................... 30 
10.1.7 
Quality Assurance and Quality Control ....................................................................... 30 
10.1.8 
Data Handling and Record Keeping ............................................................................ 30 
10.1.9 
Protocol Deviations ........................................................................................................ 31 
10.1.10 
Publication and Data Sharing Policy ........................................................................... 31 
10.1.11 
Conflict of Interest Policy .............................................................................................. 32 
10.2 
Additional Considerations ................................................................................................................. 32 
10.3 
Abbreviations and Special Terms ................................................................................................... 32 
REFERENCES .......................................................................................................................................................... 33 
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
1 
STATEMENT OF COMPLIANCE 
 
This trial will be carried out in accordance with the United States (US) Code of Federal Regulations 
(CFR) applicable to clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 
312, and/or 21 CFR Part 812) and research best practices.  The PI and all study team members 
who are responsible for the conduct, management, or oversight of this study will complete Human 
Subjects Protection training and clinical research best practices. 
 
The protocol, informed consent document, recruitment materials, and all participant materials 
will be submitted to IRBMED for review and approval. Approval of both the protocol and the 
consent documents will be obtained before any participant is consented. Any amendment to the 
protocol will be submitted for review and approval by IRBMED before the changes are 
implemented to the study. All changes to the consent form(s) will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
2 
INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines, as described in the Statement of Compliance above. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
7/10/24 
 
Name*:  Sara Till, MD, MPH 
 
Title*: Principal Investigator, Assistant Professor of Obstetrics and Gynecology 
 
Investigator Contact Information 
Affiliation*: University of Michigan 
Address: 1500 E. Medical Center Dr.  
Telephone: 734-232-1333 
Email: tillsa@med.umich.edu 
 
 
 
 
 
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
 
Title: 
Novel web-based, self-directed intervention for chronic pelvic pain 
 
Grant Number: 
1K23HD09928301A1 
 
Study Description: 
We propose to conduct a pilot randomized controlled trial to evaluate 
preliminary effectiveness of a web-based, self-management program 
for patients with CPP and phenotypic factors that predict positive 
response. Our overall hypothesis is patients with CPP who have access 
to this novel intervention will demonstrate improved in pain, physical 
function, and quality of life. 
 
Objectives*: 
 
Primary Objective:  
- 
To evaluate effectiveness of the intervention by comparing 
pain interference among intervention group versus control 
group following the intervention. 
Secondary Objectives:  
- 
To compare pain intensity among intervention group versus 
control group.  
- 
To compare physical function and health-related self-efficacy 
among intervention group versus control group.  
 
Endpoints*: 
Primary Endpoint:  
- 
PROMIS Pain Interference SF 4a at 3 months.  
Secondary Endpoints:  
- 
PROMIS pain intensity from baseline to 3 months.  
- 
PROMIS Self Efficacy for Managing Symptoms SF 4a at 3 
months 
Study Population: 
We will recruit 69 women (female sex assigned at birth) with chronic 
pelvic pain. 
 
Phase* or Stage: 
Stage 1 on NIH Stage Model for behavioral interventions 
 
Description of 
Sites/Facilities Enrolling 
Participants: 
Department of Obstetrics and Gynecology and the Chronic Pain and 
Fatigue Research Center (CPFRC) at the University of Michigan. Patients 
will be recruited from the Chronic Pelvic Pain and Endometriosis 
referral clinic at Michigan Medicine, where our group of specialty-
trained gynecologists see approximately 150 patients with CPP every 
month. 
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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Description of Study 
Intervention/Experimental 
Manipulation: 
Patients will be randomized (2:1) to participation in a 6-month web-
based, integrative self-management program in addition to usual care 
as determined by the patient’s CPP provider (intervention group), or to 
a web-based symptom monitoring program in addition to usual care 
(control group). The intervention is comprised of a self-guided 
program, My Pelvic Plan, that combines education on several individual 
conditions that often contribute to CPP, and will include instruction on 
cognitive and behavioral restructuring, self-administration of 
acupressure, engaging in physical activity, and a brief introduction to 
pelvic floor physical therapy techniques.  
 
Study Duration*: 
3 years 
 
Participant Duration: 
7 months 
1.2 
SCHEMA  
 
Flow Diagram 
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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1.3 
SCHEDULE OF ACTIVITIES  
 
 
 
Pre-consent 
0 month 
Day 0 + 14 
1 month 
Day 30 + 14 
2 month 
Day 60 + 14 
3 month  
Day 90 + 14 
4 month 
Day 120 + 14 
5 month 
Day 150 + 14 
6 month  
Day 180 + 14 
Review eligibility 
x 
x 
 
 
 
 
 
 
Consent 
 
x 
 
 
 
 
 
 
Randomization 
 
x 
 
 
x 
 
 
 
Adverse Event Reporting 
 
x 
x 
x 
x 
x 
x 
x 
Intervention 
 
 
 
 
 
 
 
 
Access My Pelvic Plan 
(Intervention group) 
 
x 
x 
x 
x 
x 
x 
x 
Access Monitoring Progress 
(Control group) 
 
x 
x 
x 
x 
x 
x 
x 
Outcome evaluation 
 
 
 
 
 
 
 
 
Questionnaire 
 
x 
 
 
x 
 
 
x 
Current treatment survey 
 
x 
 
 
 
 
 
x 
Utilization survey 
(Intervention group) 
 
 
x 
x 
x 
x 
x 
x 
Focus group 
(n=20, Intervention group) 
 
 
 
 
x 
 
 
 
 
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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2 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
 
Chronic Pelvic Pain (CPP) is a debilitating problem that afflicts 15-20% of reproductive age women.1 Pain 
and suffering often persist despite treatment, and lead to decreased productivity and reduced quality of 
life.2,3 The limitations of current surgical and pharmacologic treatments for CPP have been well 
documented. 
  
One of the most significant clinical challenges in CPP is predicting which treatment is likely to be 
effective for an individual patient, due in large part to the heterogeneity of CPP. Management of other 
chronic conditions has improved with development of clinical phenotypes, which help clinicians more 
quickly match patients with effective treatments. However, clinical phenotypes have not yet been 
extensively explored in CPP. 
  
We propose to develop a web-based, self-management program for patients with CPP and to conduct a 
pilot randomized controlled trial to evaluate preliminary effectiveness of the intervention and 
phenotypic factors that predict positive response. Our overall hypothesis is patients with CPP who 
receive access to this web-based self-management program, My Pelvic Plan, will demonstrate 
improvements in pain, health-related self-efficacy, physical function, and quality of life with this 
integrative self-management approach. This project will generate preliminary data to support an R01 
application to perform an RCT efficacy trial with a focus on patient phenotyping. 
 
2.2 
BACKGROUND  
 
The significant suffering caused by chronic pelvic pain (CPP) leads to multiple surgeries and long-term 
medical therapies at a cost of $2.8 billion annually.1 Women with CPP suffer tremendously: they use 
three times more medications, have four times more gynecologic surgery, and are five times more likely 
to undergo hysterectomy than women without CPP.1 Pain and suffering often persist despite these 
treatments, and lead to decreased productivity, diminished emotional well-being, altered life course 
trajectory, low work productivity, impaired sexual function and reduced quality of life. Many patients 
with CPP report hypervigilance and fear around behaviors that may exacerbate symptoms and 
demonstrate disadvantageous psychological responses to pain such as dissociation, avoidance, and 
reduced self-efficacy.4,5 
  
Non-pharmacologic therapies are increasingly being utilized in other chronic pain conditions with 
promising results. Cognitive Behavioral Therapy (CBT), acupressure, and physical activity interventions 
have been shown to be effective in a wide range of chronic pain conditions.6,7  Among patients with CPP, 
several small studies have demonstrated efficacy of CBT, acupressure, and physical activity 
interventions.8-11  
  
 
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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Cognitive Behavioral Therapy (CBT) is an evidence-based practice that has been widely applied to 
chronic pain populations.6 Physical activity interventions have demonstrated significant improvements 
in pain, quality of life, physical function, depression, anxiety, pain-related self-efficacy, and 
catastrophizing in patients with fibromyalgia, IBS, low back pain, and osteoarthritis.12-14 Acupuncture and 
acupressure interventions have demonstrated improvements in pain, physical function, and fatigue in 
patients with fibromyalgia and low back pain.15,16 Many patients have difficulty participating in these 
CBT interventions due to limited availability of providers, particularly in rural or underserved areas, lack 
of insurance coverage, and high out-of-pocket costs. Web-based self-management programs help to 
reduce barriers to access, and many have been shown to be as effective as traditional face-to-face 
interventions.9,17  
  
2.3 
RISK/BENEFIT ASSESSMENT  
 
2.3.1 KNOWN POTENTIAL RISKS  
 
Breach of confidentiality: Participation in this study poses a risk for breach of confidentiality. Several 
measures have been taken to reduce the risk of breach of confidentiality. These include training of study 
team members, electronic and physical security measures for data capture and storage and collecting a 
minimum of identifiable information for each individual project. Breach of confidentiality will be 
considered a “definitely related” Serious Adverse Event. As such, it will be reported to the University of 
Michigan IRB within 7 days of occurrence, and a remediation plan will be put in place immediately. 
Discomfort associated with being asked personal questions about health history and the completion of 
questionnaires: Any participant becoming distressed while completing questionnaires will be 
encouraged to seek clarification of any questions that they find to be unclear or troubling. All 
participants are told that they have the option to terminate participation without penalty and/or will be 
assisted in arranging medical/ psychiatric help including, if necessary, emergency treatment if needed. 
Symptom exacerbation: We do not anticipate that the My Pelvic Plan program is likely to place patients 
at an increased risk of symptom exacerbations. Cognitive and behavioral programs have been shown to 
be low risk for adverse events.18 However, we will discuss that new activities, such as physical therapy 
and exercise, sometimes precipitate a temporary increase in myofascial pain, and will offer basic 
anticipatory guidance. This is a well-described phenomenon and is not unique to this program. Our CPP 
provider have extensive expertise in determining whether exacerbations are typical given possible 
triggers and can offer individual guidance on whether additional evaluation is warranted.  
During the study period, all patients will receive usual care as determined by their CPP provider and PCP. 
While we will not enroll patients who are planning to undergo surgery during the study period, patients 
will be able to proceed with any intervention determined to be necessary by their medical providers, 
including surgery and medication changes, without being excluded from our analysis. We will collect 
data on interim surgery or medication changes at the 3 and 6-month follow up periods.  
Patients with chronic pelvic pain have episodic symptom exacerbations, which can sometimes be 
predicted or explained by known triggers such as menses, but often appear idiopathic and 
unpredictable. While the My Pelvic Plan program will contain information and skills to help manage 
exacerbations, the program will repeatedly clarify that this is not a replacement for professional medical 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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advice, and they should contact their provider if they have urgent concerns. They will maintain the same 
level of access to their providers as any other patient, which they can utilize should they have a 
symptom exacerbation during the study period. 
Patients with chronic pelvic pain have higher rates of depression compared to patients without chronic 
pain conditions. While we do not anticipate that the My Pelvic Plan program is likely to exacerbate 
symptoms of depression, we want to ensure that patients who are suffering from severe depression 
receive appropriate treatment. Therefore, PROMIS Depression SF 8b will be scored immediately. If a 
patient receives a score > 70, consistent with severe depression, they will receive a call from a study 
member who will complete a brief screen for suicidal ideation. If positive, the patient will be referred to 
the University of Michigan Psychiatric Emergency Service. If no suicidal ideation, we will offer referral to 
University of Michigan Depression Center or offer to contact the patient’s PCP to help facilitate 
evaluation and treatment.  
2.3.2 KNOWN POTENTIAL BENEFITS  
 
Based on data from similar interventions in patients with other chronic pain conditions, we anticipate that 
patients in the intervention group will see modest improvement in pain interference, physical function, 
and health-related self-efficacy associated with participation in this study (immediate and short-term 
potential benefits).  
 
We also anticipate that the information gathered from this pilot study will allow us to refine the program 
to best meet the needs of similar patients with chronic pelvic pain. The long-term potential benefits 
include assisting with the refinement of an accessible intervention that will eventually be made publicly 
available at no cost to patients.  
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The anticipated risks to study participants are reasonable given the nature of the study. There are few 
reasonable alternatives to gathering detailed symptom and quality of life information outside of these 
validated questionnaires. The proposed benefits of the study outweigh the anticipated risks of study 
participation. 
At any time, the participants may withdraw from the study. Participants may refuse to answer any 
questions that may be uncomfortable. This message is conveyed in all during the informed consent 
process and during instructions to participants. To minimize any risk of a breach in confidentiality, all 
study staff will be trained, physical security measures for data capture and storage will be used and we 
will only collect a minimum of identifiable information. Records will be kept confidential to the extent 
provided by Federal, State, and local law. Nevertheless, subjects are informed that the sponsor and the 
Institutional Review Board for the use of human subjects in research may inspect the records of this 
investigation. 
3 
OBJECTIVES AND ENDPOINTS  
 
Outcome type 
Measure description title 
Specific measurement 
Timeframe 
Primary 
outcome 
To evaluate effectiveness of 
the intervention by comparing 
PROMIS Pain Interference 
SF 4a  
3 months (primary 
endpoint) and 6 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
9 
pain interference among 
intervention group versus 
control group following the 
intervention. 
months (secondary 
endpoint). 
Secondary 
outcomes 
To compare pain intensity 
among intervention group 
versus control group. 
PROMIS pain intensity 1a  
3 months (primary 
endpoint) and 6 
months (secondary 
endpoint). 
 
To compare health-related self-
efficacy among intervention 
group versus control group. 
PROMIS Self Efficacy for 
Managing Symptoms SF 4a  
3 months (primary 
endpoint) and 6 
months (secondary 
endpoint). 
Tertiary 
outcomes 
To explore additional pain 
characteristics among 
intervention group versus usual 
care group. 
painDETECT 
Fibromyalgia Survey Score 
3 months (primary 
endpoint) and 6 
months (secondary 
endpoint). 
 
 
To explore quality-of-life 
measures among intervention 
group versus control group 
PROMIS Physical Function 
SF 4a 
PROMIS Anxiety SF 4a 
PROMIS Depression SF 4a 
PROMIS Fatigue SF 4a 
PROMIS Sleep Disturbance 
SF 4a 
PROMIS Sleep-related 
impairment SF 4a 
PROMIS Ability to 
participate in social roles 
and activities SF 4a 
PROMIS cognitive function 
– abilities 
PROMIS emotional support 
Pain Catastrophizing Scale 
Female Sexual Function 
Index 
Patient Global Impression 
of Change 
Complex Multiple 
Symptom Inventory 
Chronic overlapping pain 
condition screener 
Connor-Davidson 
Resilience Scale 
Relationship Assessment 
Scale  
CPP self-report opioid 
benzo assessment 
3 months (primary 
endpoint) and 6 
months (secondary 
endpoint). 
 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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4 
STUDY DESIGN 
 
4.1 
OVERALL DESIGN 
 
This Stage 1 intervention will conduct a pilot randomized controlled trial to evaluate preliminary 
effectiveness of a web-based, self-management program for patients with CPP and phenotypic factors 
that predict positive response. Our overall hypothesis is patients with CPP who have access to this 
intervention will demonstrate improved in pain, physical function, and quality of life. 
   
This trial will be conducted at Michigan Medicine (single site) and all patients will recruited from 
the Chronic Pelvic Pain and Endometriosis referral clinic.  
 
Random allocation will occur in 2:1 ratio (intervention:control) utilizing permuted blocks of 4 without 
stratification. Allocation concealment will be ensured using computer generated central randomization 
and will occur after patient has signed the consent form. The study team member who generates 
random allocation sequence will not be involved in recruitment or enrollment. Patients will be blinded 
to their group assignment. Study team members involved in outcome assessment will be blinded to 
group assignment. The patient’s CPP provider who will continue to provide usual care for pelvic pain will 
also be blinded from group assignment.  
 
Patients will be randomized to participation in a 6-month web-based, integrative self-management 
program (https://www.mypelvicplan.com/) in addition to usual care as determined by the patient’s CPP 
provider (intervention group), or to a web-based symptom monitoring program 
(https://monitoringprogress.org/) in addition to usual care (control group). The intervention is 
comprised of a self-guided program that combines education on several individual conditions that often 
contribute to CPP, and will include instruction on cognitive and behavioral restructuring, self-
administration of acupressure, engaging in physical activity, and a brief introduction to pelvic floor 
physical therapy techniques. 
  
Following enrollment, patients will complete online baseline questionnaires, which will include relevant 
medical and gynecologic history, pain symptoms, quality of life measures, and current treatments for 
pelvic pain symptoms (medications, physical therapy, etc.). After completing questionnaires, patients in 
the intervention group will receive access to the intervention website and those in the control group will 
receive access to the symptom monitoring website.  Patients will be instructed to continue routine 
follow up and usual care with their established CPP provider throughout the study.  
 
Patients will receive a questionnaire to evaluate pain symptoms and quality of life measures at 3-month 
interval (primary endpoint) and 6-month interval (secondary endpoint). After completion of 3-month 
questionnaire battery, we will be performing focus groups for approximately one-half of the patients in 
the intervention group (n=20) in order to obtain in-depth feedback regarding the program.  
 
Cannabis use survey 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
Protocol #HUM000231526 
 
10 July 2024 
 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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A participant is considered to have completed the study if they have completed the baseline questionnaire 
and at least the 3-month questionnaire. Patients in the intervention group may decline this invitation to 
participate in the focus groups and still be considered to have completed the study.  
  
The study will conclude once all patients have completed the final 6-month questionnaires. Patients may 
choose to withdraw from the study at any time. If a patient withdraws before the 3-month 
questionnaire is sent, we will attempt to replace them with another eligible patient. 
4.2 
SCIENTIFIC RATIONAL FOR STUDY DESIGN 
 
Non-pharmacologic therapies are increasingly being utilized in other chronic pain conditions with 
promising results. The My Pelvic Plan program includes multiple non-pharmacologic therapies, including 
cognitive behavioral techniques, acupressure, and physical activity.  
 
Cognitive Behavioral Therapy (CBT) is an evidence-based practice that has been widely applied to 
chronic pain populations including fibromyalgia,19 low back pain,20 and irritable bowel syndrome (IBS).7 
Among patients with CPP, several small studies have demonstrated efficacy of CBT interventions.8,21  
 
Physical activity interventions have demonstrated significant improvements in pain, quality of life, 
physical function, depression, anxiety, pain-related self-efficacy, and catastrophizing in patients with 
fibromyalgia, IBS, low back pain, and osteoarthritis.12,13,22 Among patients with CPP, several small studies 
have demonstrated efficacy of physical activity interventions.10,11 
 
Acupuncture and acupressure interventions have demonstrated improvements in pain, physical 
function, and fatigue in patients with fibromyalgia and low back pain.15,16 Among patients with CPP, 
several small studies have demonstrated efficacy acupressure interventions.9,23  
 
Many patients have difficulty participating in these non-pharmacologic interventions due to limited 
availability of providers, particularly in rural or underserved areas, lack of insurance coverage, and high 
out-of-pocket costs. Web-based self-management programs help to reduce these barriers, and many 
have been shown to be as effective as traditional face-to-face interventions. By creating a web-based 
program that integrates the above nonpharmacologic interventions, we aimed to address gaps in 
availability and access for a patient population that is likely to greatly benefit from an integrative 
treatment approach. 
 
Because CPP is a heterogeneous condition, we hypothesize that there will not be one version of an 
intervention that it effective for all patients. Our goal is to expose patients to several treatment 
modalities and allow them to build a program that meets their specific needs. As this is an exploratory 
study, we will incorporate several types of treatment modalities – cognitive/behavioral, acupressure, 
physical therapy, and physical activity – and allow patients to utilize each as they wish. Evaluating 
utilization and preliminary effectiveness of each of the modalities will inform how we adapt the 
intervention for future studies. Effect sizes of individual non-pharmacologic interventions are typically 
small (0.15-0.3).18,24 However, interventions that integrate several of these modalities appear to have 
substantially improved efficacy (0.3-0.8),25-27 indicating possible synergistic rather than additive effects. 
Effect sizes for pharmacologic treatments for chronic pain conditions are similarly modest.28 
 

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Limited effects of both pharmacologic and non-pharmacologic therapies seem to be due to the fact that 
response is often bimodal, with patients typically responding either minimally or robustly, in which case 
the average effect appears quite modest. Therefore, experts in chronic pain research have advocated for 
a shift toward identifying responders when investigating treatments, which can better inform 
development of personalized treatment strategies. For this reason, we will gather preliminary 
information about patient phenotyping – whether certain factors predict which patients tend to respond 
most robustly to various treatments. We will be performing an exploratory analysis focused on 
development of phenotypes within chronic pelvic pain. We will compare overall responders versus non-
responders and will also explore response to specific skills within the program. We intend to focus more 
on this patient phenotyping exploration in future studies.  
 
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
• 
Woman (female sex assigned at birth, may include cis-gender, trans-gender, nonbinary)  
• 
At least 18 years old  
• 
have chronic pelvic pain, defined as moderate to severe pelvic pain that is ≥ 4 on a 0-10 numeric 
rating scale (worst pain during the day) for ≥ 6-month duration, and is non-cyclic, occurring for 
at least 14 days of each month.  
• 
must be currently receiving care within Department of Obstetrics and Gynecology at the 
University of Michigan for treatment of chronic pelvic pain.  
• 
Access to internet via computer or smartphone  
• 
English-language proficiency (current version of the website is in English) 
• 
We will attempt to recruit a diverse group of patients, with attention to diversity in race, 
ethnicity, education level, rural vs urban locality, sexual orientation, and gender identification.  
5.2 
EXCLUSION CRITERIA 
 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
• 
underwent gynecologic surgery within 3 months of screening visit 
• 
plan to undergo gynecologic surgery within 6 months following screening visit 
• 
pregnant (self-reported) at time of screening visit. Will not exclude patients who become 
pregnant during the course of the study.  

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• 
severe physical impairment precluding participating in internet-based program (for example, 
complete blindness or deafness) 
• 
current psychiatric disorder with history of psychosis (for example, schizophrenia, 
schizoaffective disorder, delusional disorder), 
• 
current suicidal ideation or suicide attempt within 2 years of screening visit. We will screen for 
severe depression and suicidality at each questionnaire time point and have developed a robust 
triage and referral plan. 
 
5.3 
SCREEN FAILURES 
 
Screen failures are defined as participants who go through screening process for eligibility but are not 
subsequently entered in the study. Individuals who do not meet the criteria for participation in this trial 
(screen failure) at time of screening because of meeting one or more exclusion criteria that are likely to 
change over time may be rescreened. Examples include pain that does not meet intensity or frequency 
threshold, recent or planned surgery outside of defined threshold, and currently undergoing cognitive 
behavioral therapy at time of screening visit. Rescreened participants will be assigned the same 
participant number as for the initial screening. 
 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
We will be using thoughtful recruitment and allocation methods to minimize bias. We will attempt to 
include a diverse group of participants for this study, with intentional recruitment to reflect diversity in 
age, race, geographic location and pelvic pain conditions. 
 
We will contact both intervention and control patients with text or email prompts to visit their 
respective website on prespecified basis with goal of increasing program utilization and study retention. 
In the first 12 weeks of the study (active phase), participants will receive a weekly text or email prompt 
directing them to a specific module or portion of their respective website. During the remaining time in 
the study (maintenance phase), all participants will receive monthly text or email prompts to visit their 
respective website. Details of the prompts for the intervention and control groups are included in 8.2 
Study evaluation and procedures. 
 
We are unable to track website utilization for specific users. However, we will send an email link to a 
survey once per month which will ask which skills (from the Managing Symptoms section of the website) 
they used in the last month regardless of whether they visited that module in the site. We assume that 
some patients will need repeated exposure to skills to gain mastery and incorporate into their routine, 
whereas other patients may visit a module once and be able to incorporate it into regular practice.  
 
Patients will receive a questionnaire battery at 3-month interval (primary endpoint) and 6-month 
interval (secondary endpoint). Patients will receive a reminder email if they have not completed the 
survey or questionnaire within 4 days, 7 days, and 14 days. Only three reminders will be sent per 
survey/questionnaire, with the exception of the 6-month survey, for which patients may receive one 
additional reminder at 21 days.  

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5.5 
COMPENSATION 
 
All patients will receive $50 for completion of each of the three questionnaires (baseline, 3-month, 6-
month). Patients in control group who complete all portions of the study will receive a total of $150. 
 
In addition, intervention patients will receive $5 for each of the six utilization surveys completed. 
Intervention patients who participate in a focus group at 3-months will receive $100. Therefore, patients 
in intervention group who complete all portions of the study will receive a total of $180-280, depending 
on focus group participation.  
 
All compensation will be managed by a study team member in conjunction with the University of 
Michigan Human Subjects Incentive Program (HSIP). Patients will be sent a gift card at time of 
completion of the baseline questionnaire. Additional compensation payments will be virtually loaded to 
the gift card upon completion of additional questionnaires. 
 
 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
 
As this is an exploratory study, we will incorporate several types of treatment modalities – 
cognitive/behavioral, acupressure, physical therapy, and physical activity – and allow patients to utilize 
each as they wish. However, we will utilize an established tailoring program to direct participants to 
particular modules or skills that are likely to be most relevant for their individual symptoms and 
characteristics. This tailoring program utilizes the baseline patient reported outcome measures (PROMIS 
29+2). Responses to each of these measures will be scored to obtain a T-score, which will then be ranked 
in order of divergence from population mean to represent relative burden of each factor.  All patients will 
receive prompts to the same modules during the first four weeks of the active phase. However, prompts 
during the next 8 weeks of the active phase will correspond to the rank order of the baseline measure T-
scores, directing patients to modules that address each of these factors.  During the maintenance phase 
of the study, all patients will receive the same monthly prompt to visit the Monitoring Progress symptom 
tracker subpage of the website.  
 
Evaluating preliminary effectiveness of the program will inform how we might adapt the intervention for 
future studies. This will also help explore preliminary information about patient phenotyping – whether 
certain factors predict which patients tend to respond most robustly to various treatments. 
 
6.2 
FIDELITY 
 

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6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
 
There is no variability in this program itself as all intervention patients have access to the same web-based 
program. While patients will receive tailored or curated prompts to visit specific modules in the program 
based on their individual symptom burden, the website itself is static.  
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
Random allocation will occur in 2:1 ratio (intervention:control) utilizing permuted blocks of 4 without 
stratification. Allocation concealment will be ensured using computer generated central randomization 
and will occur after patient has signed the consent form. . Enrollment will occur on a rolling basis until 
69 patients have been enrolled. The study team member who generates random allocation sequence 
will not be involved in recruitment or enrollment.  
 
Both patients and outcome assessors will be blinded to study group assignment. During recruitment, we 
will state that we are testing two different web-based approaches for self-management for chronic pelvic 
pain, so patients will not be aware of which study group they are enrolled in. Patients will be contact at 
essentially the same intervals throughout the study period to further maintain blinding. We will attempt 
to blind the patient’s CPP provider as to their group status but are unable to control the possibility that a 
patient mentions the intervention to their provider. We will ask providers not to comment about group 
status or discuss the intervention in detail with patients to maintain patient blinding to as great an extent 
as possible.  
 
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
 
Each month, we will ask intervention group participants to indicate which skills they have utilized in the 
past month. However, we are unable to track website utilization for individual patients based on the 
current website design. 
 
Relative to questionnaires, we will require completion of baseline questionnaires in order to participate 
in the study. We will not dismiss patients from participating if they do not complete questionnaires but 
will send multiple reminders and monetary incentives for participating.  
 
 
6.5 
CONCOMITANT THERAPY 
 
All patients will receive usual care as recommended by their CPP provider throughout the study. Our group 
of CPP providers utilize a fairly similar, multimodal approach for managing chronic pelvic pain. This 
commonly includes hormonal suppression, physical therapy, muscle relaxants, and centrally acting 
neuropathic medications. The specific strategies are highly dependent on the conditions contributing to 
pain symptoms in an individual patient. Of note, we utilize shared decision-making with patients, which 
means that some patients choose not to utilize a treatment that we may typically recommend as first-line 
therapy for a particular condition. Therefore, we anticipate that there will be variability in treatments 

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utilized across patients. We will assess treatments utilized at each questionnaire time point and will 
perform exploratory analyses to assess impact on primary and secondary outcomes.  
 
While we will exclude patients who have undergone gynecologic surgery within 3 months of screening 
visit, plan to undergo gynecologic surgery within 6 months following screening visit, are currently 
pregnant, at time of screening visit, patients will be able to proceed with any intervention determined to 
be necessary by their medical providers, including surgery and medication changes, without being 
excluded from our analysis. We also will not exclude patients who become pregnant during the study. We 
will collect data on interim surgery or medication changes at the 6-month follow up period.  
 
 
6.5.1 RESCUE THERAPY 
Patients may use rescue therapies as recommended by their CPP provider or other physician as part of 
usual care. The only additional rescue intervention to be initiated directly by the study team is to assess 
for severe depression at time of questionnaire submission (baseline, 3-month, 6-month). If a patient 
screens positive for severe depression (defined by score >70 on PROMIS Depression SF 8b), they will 
receive a call from a study member who will complete a brief screen for suicidal ideation. If positive, the 
patient will be referred to the University of Michigan Psychiatric Emergency Service. If no suicidal 
ideation, we will offer referral to University of Michigan Depression Center or offer to contact the 
patient’s PCP to help facilitate evaluation and treatment.  
 
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
After patients are randomized to group and complete baseline questionnaire, we will not discontinue 
access to the intervention for the duration of the 6-month study period, despite new medical/psychiatric 
diagnoses including pregnancy or undergoing gynecologic surgery.  Patients may elect to withdraw from 
the study as described below.  
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
   
Patients may choose to withdraw from the study at any time. If a patient withdraws before the 3-month 
questionnaire is sent, we will attempt to replace them with another eligible patient 
 
7.3 
LOST TO FOLLOW-UP 
Patients will receive an email with a link to questionnaires and utilizations surveys at each time point 
specified above. If questionnaires are not completed within 4 days, an automatic reminder email will be 

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sent. If questionnaires are not completed within 7 days, a study member will call with a reminder. If 
questionnaire is not completed with 14 days, a study member will call with another reminder. Patient 
will be considered lost to follow up if they fail to complete the 6-month questionnaire within 21 days 
after survey invitation.  
We will not exclude or dismiss patients based on completion of 6-month questionnaire or monthly 
utilization survey as these are not essential for the primary outcome.  
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
SCREENING PROCEDURES 
 
We will be using thoughtful recruitment and allocation methods to minimize bias. Our group of 
specialty-trained gynecologists see approximately 150 patients per month in this referral clinic. Each 
returning patient will receive a brochure containing a brief description of the study and an interest sheet 
during their check-in. A physician may assess interest if they feel that the patient may be an appropriate 
candidate. A study team member will also screen patients scheduled for return visits in the clinic and 
contact potentially eligible patients via text or email to inform them that they may be eligible for the 
study. We will not recruit new patients during this pilot study as patients often initiate a number of new 
treatments following the initial visit and we suspect that it might be more challenging to differentiate 
effect of the intervention versus treatment plan in this population.  
 
A study team member will contact interested patients to assess eligibility and confirm interest and obtain 
consent (electronic). Potential subjects will be contacted up to seven times (by telephone, text, portal 
message, or email) in order to establish contact. Entry as a subject requires passing a telephone screen to 
confirm eligibility.  
 
8.2 
STUDY EVALUATION AND PROCEDURES 
 
Once  eligibility and interest are confirmed,  the study team member will send an email link to an electronic 
version of the consent form. The study team member and patient will review study consent verbally over 
the telephone and answer any questions. Consent forms describing in detail the study intervention, study 
procedures, and risks will be given to the participant. Consent forms will be signed and stored 
electronically. We have elected to perform this combination of verbal and online consent as opposed to 
a face-to-face consent as the majority of patients from our referral clinic travel between 1-4 hours to 
reach our clinic. One of goals of this intervention is to expand access and limit barriers related to travel 
that our patients typically encounter. Therefore, we felt that requiring subjects to return for a visit 
specifically for a face-to-face consent would impose too great a burden for many participants, and that 
this approach was reasonable given the remote contact utilized in other aspects of this study. 
 
Random allocation will occur in 2:1 ratio (intervention:control) utilizing permuted blocks of 4 without 
stratification. Allocation concealment will be ensured using computer generated central randomization 
and will occur after patient has signed the consent form. The study team member who generates 
random allocation sequence will not be involved in recruitment or enrollment. Patients will be blinded 
to their group assignment. Study team members involved in outcome assessment will be blinded to 

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group assignment. The patient’s specialty gynecologist who will continue to provide usual care for pelvic 
pain will also be blinded to group assignment.  
 
Enrollment will occur on a rolling basis until 69 patients have been enrolled. We anticipate that we will 
likely need to screen approximately 200 patients in order to enroll 69 participants over an 18-month 
period.   We will attempt to recruit a diverse group of patients, with attention to diversity in race, 
ethnicity, age, education level, rural vs urban locality, sexual orientation, and gender identification.  
 
Following enrollment, patients will complete online baseline questionnaires, which will include current 
treatments for pelvic pain symptoms (medications, physical therapy, etc.). After completing 
questionnaires, patients in the intervention group will receive access to the intervention website and 
those in the control group will receive access to the symptom monitoring website.   
 
Intervention group 
 
Patients in the intervention group will receive access to the My Pelvic Plan website 
(https://www.mypelvicplan.com/), which is a self-directed program which integrates patient education 
about conditions that frequently contribute to pelvic pain, as well as instruction on cognitive and 
behavioral restructuring, self-administration of acupressure, engaging in physical activity, and a brief 
introduction to pelvic floor physical therapy techniques. They will have open access to the program over 
the 6-month intervention period. The intervention will be comprised of an active (12-week) phase and a 
maintenance (3-month) phase. During the active phase, we will use an established tailoring program to 
direct participants to particular modules or skills that are likely to be most relevant for their individual 
symptoms and characteristics. All intervention participants will receive a weekly text or email prompt 
directing them to a specific module. All participants will receive prompts to the same modules for the 
first four weeks of the study. During the next 8 weeks, participants will receive prompts to modules that 
corresponded to their most impactful symptoms on their baseline questionnaires. Following the 12-
week active phase, all participants will enter the maintenance phase, during which they will receive 
monthly prompts to Monitoring Progress symptom tracker module.  
 
Patients will have open access to the program over the 6-month intervention period. While they will 
receive text or email prompts to visit specific modules, they will ultimately choose how they navigate 
and utilize the program and we will not prescribe a specific schedule or utilization frequency. 
 
We are unable to track website utilization for specific users. However, we will send an email link to a 
survey once per month which will ask which skills (from the Managing Symptoms section of the website) 
they used in the last month regardless of whether they visited that module in the site. We assume that 
some patients will need repeated exposure to skills to gain mastery and incorporate into their routine, 
whereas other patients may visit a module once and be able to incorporate it into regular practice.  
 
Patients will receive a questionnaire battery at 3-month interval (primary endpoint) and 6-month 
interval (secondary endpoint). Patients will receive an email with a link to questionnaires at 3 months 
and again at 6 months. The 6-month questionnaire will also include questions regarding current 
treatments for pelvic pain symptoms, including interval surgery.  
 
After completion of 3-month questionnaire battery, we will be performing focus groups for 
approximately one-half of the patients in the intervention group (n=20) in order to obtain in-depth 
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participants for these focus groups, with intentional recruitment to reflect diversity in age, race, 
geographic location and pelvic pain conditions. These sessions will focus on skills and modules that were 
most impactful and whether participants believe that combining the intervention with an individual 
coach or an online community might be beneficial.  
 
Control group 
Patients in the control group will undergo an active control intervention in which they receive open 
access to a separate website (https://monitoringprogress.org/) that contains only the Monitoring 
Progress symptom tracker subpage over the 6-month study period. Control group participation will also 
be divided into an active (12-week) phase and a maintenance (3-month) phase. Similar to the 
intervention group, the control group will receive a weekly text or email prompt directing them to track 
a specific symptom or activity during the active phase of that study. During the maintenance phase of 
the study, they will receive monthly prompts to the Monitoring Progress subpage (without prompting to 
a specific symptom or activity).  
 
Control participants will receive a questionnaire battery at 3-month interval (primary endpoint) and 6-
month interval (secondary endpoint). 
 
Both patients in the intervention and control groups will receive contact from the study team at the 
same intervals throughout the study. If questionnaires are not completed within 4 days, an automatic 
reminder email will be sent. If questionnaires are not completed within 7 days, a study member will call 
with a reminder. If questionnaire is not completed with 14 days, a study member will call with another 
reminder. Patient will be considered lost to follow up if they fail to complete the 6-month questionnaire 
within 21 days after survey invitation. Both intervention and control groups will continue to follow with 
their specialty gynecologist and will receive usual care throughout the study period. On average, 
patients follow up every 3-4 months in this clinic per their physician recommendation and we will not 
recommend any specific changes to usual care follow up as part of this study.  
  
A participant is considered to have completed the study if they have completed the baseline questionnaire 
and the 3-month questionnaire.  
 
After completion of 3-month questionnaire, we will be performing focus groups for approximately one-
half of the patients in the intervention group (n=20) in order to obtain in-depth feedback regarding the 
program and potential adjunct therapies for future studies. Patients in the intervention group may 
decline this invitation and still be considered to have completed the study.  
  
The study will conclude once all patients have completed the final 6-month questionnaires. Patients may 
choose to withdraw from the study at any time. If a patient withdraws before the 3-month 
questionnaire is sent, we will attempt to replace them with another eligible patient. 
 
8.3 
SAFETY ASSESSMENTS 
 
The study team will assess for severe depression at time of questionnaire submission (baseline, 3-
month, 6-month). If a patient screens positive for severe depression (defined by score >70 on PROMIS 
Depression SF 4b), they will receive a call from a study member who will complete a brief screen for 
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Emergency Service. If no suicidal ideation, we will offer referral to University of Michigan Depression 
Center or offer to contact the patient’s PCP to help facilitate evaluation and treatment. 
 
 
8.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.4.1 DEFINITION OF ADVERSE EVENTS 
 
This protocol uses the definition of adverse event from 21 CFR 312.32 (a): any untoward medical 
occurrence associated with the use of an intervention in humans, whether or not considered intervention 
related. 
 
This intervention is considered to carry low risk to subjects. Patients with chronic pelvic pain have 
episodic symptom exacerbations, which can sometimes be related to known triggers such as menses or 
intercourse, but often appear idiopathic or unpredictable. Additionally, patients with chronic pain 
conditions have higher rates of depression compared to their peers and we want to ensure that patients 
suffering from severe depression receive appropriate treatment.   
 
Therefore, we will consider the following to be adverse events: 
- 
Pain exacerbation prompting evaluation in emergency department 
- 
Pain exacerbation prompting scheduled gynecologic surgery 
- 
Screen positive for suicidal ideation in discussion with study team member following up on 
screen for severe depression   
 
8.4.2 DEFINITION OF SERIOUS ADVERSE EVENTS  
 
We will consider the following to be serious adverse events: 
- 
Pain exacerbation prompting inpatient hospitalization 
- 
Pain exacerbation prompting urgent or emergent surgical evaluation 
- 
Suicide attempt or significant deterioriation of psychiatric conditions resulting in inpatient 
psychiatric hospitalization 
 
8.4.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.4.3.1 SEVERITY OF EVENT 
 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines will 
be used to describe severity.  
 
• 
0 – No AE 
• 
1 - Mild  AE – Events require minimal or no treatment and do not interfere with the participant’s 
daily activities.  

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• 
2 – Moderate AE – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
3 – Severe AE – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate too “serious”. 
• 
4 – Life threatening or disabiling AE 
• 
5 – Fatal AE 
 
8.4.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
All adverse events (AEs) will have their relationship to study procedures, including the intervention, 
assessed by an appropriately trained clinician based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below.  
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study procedures administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study procedures should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the study procedures, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal.  
• 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of study procedures). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study procedures administration makes a causal relationship improbable 
(e.g., the event did not occur within a reasonable time after administration of the study 
procedures) and in which other drugs or chemicals or underlying disease provides plausible 
explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study procedures administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
 
 
8.4.3.3 EXPECTEDNESS  
 
A clinician with appropriate expertise in chronic pelvic pain will be responsible for determining whether 
an adverse event (AE) is expected or unexpected. An AE will be considered unexpected if the nature, 

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severity, or frequency of the event is not consistent with the risk information previously described for the 
study procedures. 
 
 
8.4.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All AEs, not otherwise precluded per the protocol, will be captured on the appropriate case report form 
(CRF). Information to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study procedures (assessed only by those with the training and authority to make 
a diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study will be 
documented appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical or psychiatric condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. Documentation of onset and duration of each episode will be 
maintained for AEs characterized as intermittent. 
 
Study coordinator will record events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation.  At 
each study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. We will 
primarily rely on patient self-report of adverse events and will not proatively search internal or external 
medical record systems to identify these.  Events will be followed for outcome information until resolution 
or stabilization. 
 
 
8.4.5 ADVERSE EVENT REPORTING  
AEs will be reported to the University of Michigan IRBMED as required and to NIH annually.  
 
8.4.6 SERIOUS ADVERSE EVENT REPORTING  
 
In consultation with the PI, a trained member of the study team will be responsible for conducting an 
evaluation of a serious adverse event and shall report the results of such evaluation to NIH and the 

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reviewing Institutional Review Board (IRB) as soon as possible, but in no event later than 10 working days 
after the investigator first learns of the event. 
 
 
8.4.7 REPORTING EVENTS TO PARTICIPANTS  
 
Serious adverse events that have been deems probably or definitely related to the intervention will be 
reported to patients within 60 days of the incident. All other adverse events, serious adverse events, and 
incidental findings will be communicated to participants along with study-related results by email or 
preferred method of communication within one year following the end of the study.   
 
 
8.5 
UNANTICIPATED PROBLEMS 
 
8.5.1 DEFINITION OF UNANTICIPATED PROBLEMS 
 
This protocol uses the definition of Unanticipated Problems as defined by the Office for Human Research 
Protections (OHRP).  OHRP considers unanticipated problems involving risks to participants or others to 
include, in general, any incident, experience, or outcome that meets all of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
8.5.2  UNANTICIPATED PROBLEMS REPORTING  
 
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB). The UP report will include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number 
• 
A detailed description of the event, incident, experience, or outcome  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP 

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To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB and to NIH as soon as 
possible, but in no event later than 10 working days after the investigator first learns of the event. 
• 
Any other UP will be reported to the IRB and NIH annually.  
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) annually. 
 
8.5.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
Unanticipated problems will be reported to participants along with adverse events, serious adverse 
events, incidental findings and study-related results by email or preferred method of communication 
within one year following the end of the study.   
 
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
 
• 
Primary Endpoint:  
We hypothesize that patients who receive the My Pelvic Plan intervention in addition to usual care 
will demonstrate improvement on PROMIS Pain Interference SF 4a from baseline to 3-month follow-
up.  Alternatively, our null hypothesis is that there will be no difference in Pain Interference from 
baseline to 3-month follow up. As this is a pilot study, we will be evaluating preliminary program 
effectiveness by comparing the intervention group to an active control group and will use this 
information to generate effect size for a trial to evaluate efficacy.   
 
 
• 
Secondary Endpoints: 
We hypothesize that patients who receive the My Pelvic Plan intervention in addition to usual care + 
symptom tracker will demonstrate improvements on PROMIS Pain Intensity and PROMIS Self 
Efficacy for Managing Symptoms SF 4a from baseline to 3-month follow-up.  Alternatively, our null 
hypothesis is that there will be no difference in Pain Intensity and Self-Efficacy from baseline to 3-
month follow up. 
 
9.2 
SAMPLE SIZE DETERMINATION 
 
As this is a pilot study, we have chosen to recruit a sample of 69 patients so that we can assess the 
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will be conducted in a future R01 application.  We are not attempting to power the analyses to detect a 
difference in our primary outcome (pain interference). 
 
In addition to pain interference, we will also examine pain intensity and health-related self-efficacy to 
assess whether these outcomes might be more appropriate primary outcomes in an efficacy trial.   
9.3 
POPULATIONS FOR ANALYSES 
 
We will use an intent to treat analysis. Primary outcome (pain interference) will be assessed at 3-months 
and 6-month data will only contribute to secondary outcomes. Given this, we will plan carry the last 
observation forward (either 3-month or baseline) for patients who are lost to follow up at 6-months.  
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
For descriptive statistics, continuous variables will be presented using means with standard deviation. 
Categorical variables will be presented using percentages with 95% confidence intervals. All tests will be 
two sided at 5% significance level. Normality will be assessed, and nonparametric tests used where 
appropriate.  
 
We will prespecify several covariates for regression models with special attention to emerging constructs 
in the pain literature, specifically FM survey score and PainDETECT, that may be associated with treatment 
response. However, we will also perform exploratory analyses given our focus on hypothesis generation.   
 
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
The primary outcome (PROMIS Pain Interference) is a continuous measure and utilizes a standardized, 
publicly available scoring system. We will report mean and standard deviation for each group.  
Given pilot RCT design, we will use a simple posttreatment comparison of pain interference at 3-months. 
We will compare means with t-test. All tests will be two-sided at 5% significance level.  Of note, data 
collected at 6-month interval will be analyzed as an exploratory outcome.  
We will estimate effect size by calculating Hedges’ g (rather than Cohen’s d because groups are different 
sizes) for pain interference at 3-months, which we will use in planning for future efficacy trial.  
As part of our exploratory analyses, we plan to categorize patients as “responders” vs “non-responders.” 
“Responder” will be defined as an improvement of at least 2.5 on PROMIS Pain Interference from 
baseline to 3-months. We will compare differences in contributing pain conditions, pain characteristics 
such as Fibromyalgia Survey Score or PainDETECT, and comorbid mental health factors that may be 
associated responder status.  We tentatively plan to use logistic regression to compare factors 
associated with responder status. We will use these exploratory analyses to inform structure of our 
future efficacy trial.  

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We will be using an intent to treat analysis. Patients may elect to skip questions on the questionnaire 
and therefore it is possible that we encounter some missing data or incomplete questionnaires. We will 
report the proportion of missing outcome per group and characteristics of patients with missing data. If 
we encounter more than 5% missing data, we plan to conduct sensitivity analyses to assess effect of 
missingness on results.    
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Secondary outcomes (PROMIS Pain Intensity and PROMIS Self-Efficacy) are also continuous measures 
and utilize a standardized, publicly available scoring system. We will use a simple posttreatment 
comparison of pain interference at 3-months. All tests will be two-sided at 5% significance level.  Of 
note, data collected at 6-month interval will be analyzed as an exploratory outcome. 
We will be using an intent to treat analysis. Patients may elect to skip questions on the questionnaire 
and therefore it is possible that we encounter some missing data or incomplete questionnaires. We will 
report the proportion of missing outcome per group and characteristics of patients with missing data. If 
we encounter more than 5% missing data, we plan to conduct sensitivity analyses to assess effect of 
missingness on results.    
 
9.4.4 SAFETY ANALYSES 
 
N/A 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
Baseline characteristics of the intervention and control groups will be compared using descriptive 
statistics, using independent samples t-test for continuous variables and chi-square/Fisher’s exact test for 
categorical variables.  All tests will be two sided with 5% significance level. Planned analyses include 
demographic information, medical and surgical history, chronic pain diagnoses (endometriosis, pelvic 
myofascial pain, irritable bowel syndrome, etc.), and current category of treatments (hormonal 
suppression, pelvic physical therapy, etc.).  
 
9.4.6 PLANNED INTERIM ANALYSES  
 
N/A 
9.4.7 SUB-GROUP ANALYSES 
 
N/A 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
N/A 
 

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9.4.9 EXPLORATORY ANALYSES 
 
We will explore preliminary phenotyping hypotheses based on demographic factors, baseline symptoms, 
comorbid conditions, and outcome predictors. We will primarily focus on changes in pain interference 
but will explore additional outcomes. We will define “responder” as a patient who demonstrates a 
minimally important difference (MID) of 2.5 on pain interference and will explore phenotypic differences 
between responders and non-responders.  
While we will explore a broad array patient-level factors including demographics, pain characteristics, 
comorbid conditions, and psychological/cognitive factors, we plan to devote special attention to 
emerging constructs in literature that are associated with response to treatment. Constructs may 
include the Fibromyalgia Survey Score, presence of endometriosis or myofascial pain diagnoses, 
duration of chronic pelvic pain, comorbid pain disorders, catastrophizing, depression, anxiety, and 
psychosocial factors. We will also correlate characteristics with utilization of overall program and of 
individual modules (i.e., did patients with higher depression scores utilize the CBT modules more 
frequently). Given that the program is in an early phase of development, we are not ready to direct 
patients to specific modules based on individual characteristics. But we hope to gather preliminary 
information in order to guide patients to particular skills in a later study.  
Baseline phenotypic differences between responders/non-responders will be conducted with ANOVA for 
continuous variables and chi-square testing/Fisher’s exact test for categorical variables.  General Linear 
Models will be used for multivariable analyses of responder status. 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 STUDY DISCONTINUATION AND CLOSURE 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study participants, investigator, funding agency, and regulatory 
authorities. If the study is prematurely terminated or suspended, the Principal Investigator (PI) will 
promptly inform study participants, the Institutional Review Board (IRB), and NIH, and will provide the 
reason(s) for the termination or suspension. Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance of study staff to the protocol  (i.e., significant protocol violations) 
• 
Data that are not sufficiently complete and/or evaluable 

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• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
The study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the IRB and NIH, or other relevant regulatory or oversight bodies (OHRP, DSMB). 
 
10.1.2 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, 
the safety and oversight monitor(s), and the sponsor(s) and funding agency. This confidentiality is 
extended to the data being collected as part of this study. Data that could be used to identify a specific 
study participant will be held in strict confidence within the research team. No personally identifiable 
information from the study will be released to any unauthorized third party without prior written approval 
of the sponsor/funding agency.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the NIH and representatives of the Institutional 
Review Board (IRB) may inspect all documents and records required to be maintained by the investigator, 
including but not limited to, medical records (office, clinic, or hospital) and pharmacy records for the 
participants in this study. 
 
The study participant’s contact information will be securely stored at the clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor/funding agency 
requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be stored at the University of Michigan within the Department of Obstetrics and Gynecology. This will not 
include the participant’s contact or identifying information. Rather, individual participants and their 
research data will be identified by a unique study identification number. The study data entry and study 
management systems used by clinical sites and by University of Michigan research staff will be secured, 
and password protected. At the end of the study, all study databases will be de-identified and archived at 
the University of Michigan. 
 
Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data Sharing Policies  
It is NIH policy that the results and accomplishments of the activities that it funds should be made available 
to the public (see https://grants.nih.gov/policy/sharing.htm). The PI will ensure all mechanisms used to 
share data will include proper plans and safeguards for the protection of privacy, confidentiality, and 
security for data dissemination and reuse (e.g., all data will be thoroughly de-identified and will not be 
traceable to a specific study participant). Plans for archiving and long-term preservation of the data will 
be implemented, as appropriate.  

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Certificate of Confidentiality  
To further protect the privacy of study participants, the Secretary, Health and Human Services (HHS), has 
issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, behavioral, clinical 
or other human subjects research funded wholly or in part by the federal government.  Recipients of NIH 
funding for human subject’s research is required to protect identifiable research information from forced 
disclosure per the terms of the NIH Policy (see https://humansubjects.nih.gov/coc/index). As set forth 
in 45 CFR Part 75.303(a) and NIHGPS Chapter 8.3, recipients conducting NIH-supported research covered 
by this Policy are required to establish and maintain effective internal controls (e.g., policies and 
procedures) that provide reasonable assurance that the award is managed in compliance with Federal 
statutes, regulations, and the terms and conditions of award. It is the NIH policy that investigators and 
others who have access to research records will not disclose identifying information except when the 
participant consents or in certain instances when federal, state, or local law or regulation requires 
disclosure. NIH expects investigators to inform research participants of the protections and the limits to 
protections provided by a Certificate issued by this Policy. 
 
10.1.3 FUTURE USE OF STORED SPECIMENS AND DATA  
 
All participant data will be securely stored throughout the duration of the study and during the analysis 
phase of the study.  
 
10.1.4 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Sara Till, MD, MPH 
Assistant Professor 
University of Michigan  
1500 E. Medical Center Dr.  
Ann Arbor, MI 48105 
734-232-1333 
tillsa@med.umich.edu 
 
 
10.1.5 SAFETY OVERSIGHT 
 
Because of the small size of the study and fairly low potential risks, the Primary Investigator (Dr. Till) and 
Primary Mentor (Dr. Clauw) (PIs) will be responsible for monitoring patient safety and protocol 
adherence.  
 

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10.1.6 CLINICAL MONITORING 
 
N/A 
 
10.1.7 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Quality control (QC) procedures will be implemented as follows: 
 
Informed consent --- Study staff will review both the documentation of the consenting process as well as 
a percentage of the completed consent documents.  This review will evaluate compliance with GCP, 
accuracy, and completeness.  Feedback will be provided to the study team to ensure proper consenting 
procedures are followed.  
 
Source documents and the electronic data --- Data will be initially captured on source documents (see 
Section 10.1.8, Data Handling and Record Keeping) and will ultimately be entered into the study 
database.  To ensure accuracy site staff will compare a representative sample of source data against the 
database, targeting key data points in that review. 
 
Should independent monitoring become necessary, the PI will provide direct access to all trial related 
sites, source data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor/funding agency, and inspection by local and regulatory authorities. 
 
 
10.1.8 DATA HANDLING AND RECORD KEEPING  
 
10.1.8.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection will be the responsibility of the clinical trial staff under the supervision of the primary 
investigator. The investigator will be responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation of 
data.   
 
Hardcopies of the screening phone visit worksheets will be provided for use as source document 
worksheets for recording data for each participant consented/enrolled in the study. All other study 
materials will be collected and recorded electronically. Data recorded in the electronic case report form 
(eCRF) derived from source documents will be consistent with the data recorded on the source 
documents.  
 

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Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into Qualtrics, a 21 CFR Part 11-compliant data capture 
system provided by the University of Michigan. The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered directly from the source documents. 
 
10.1.8.2 STUDY RECORDS RETENTION  
 
Study documents will be retained for a minimum of 3 years after study completion.  
 
 
10.1.9 PROTOCOL DEVIATIONS   
 
The study team will review protocol deviations on an ongoing basis and will implement corrective actions 
when the quantity or nature of deviations are deemed to be at a level of concern. We will not classify 
missed questions on surveys or missing surveys (other than the primary outcome) as protocol deviations.  
 
It will be the responsibility of the primary investigator to use continuous vigilance to identify and report 
deviations within 30 working days of identification of the protocol deviation, or within 15 working days of 
the scheduled protocol-required activity. All deviations will be addressed in study source documents, 
reported to NICHD Program Official. Protocol deviations will be sent to the reviewing Institutional Review 
Board (IRB) per their policies. The site investigator will be responsible for knowing and adhering to the 
reviewing IRB requirements. Further details about the handling of protocol deviations will be included in 
the MOP. 
 
10.1.10 
PUBLICATION AND DATA SHARING POLICY  
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed 
journals.  Data from this study may be requested from other researchers 3 years after the completion of 

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the primary endpoint by contacting the primary investigator. Considerations for ensuring confidentiality 
of these shared data are described in Section 10.1.2. 
 
10.1.11 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a way 
that is appropriate to their participation in the design and conduct of this trial. The study leadership in 
conjunction with the NICHD has established policies and procedures for all study group members to 
disclose all conflicts of interest and will establish a mechanism for the management of all reported 
dualities of interest. 
 
10.2 ADDITIONAL CONSIDERATIONS 
 
N/A 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
ITT 
Intention-To-Treat 
MOP 
Manual of Procedures 
NICHD 
National Institute of Child Health and Human Development 
NIH  
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
UP 
Unanticipated Problem 
US 
United States 

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REFERENCES  
 
1. 
Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege JF. Chronic pelvic pain: prevalence, 
health-related quality of life, and economic correlates. Obstetrics & Gynecology 1996;87:321-7. 
2. 
Jones G, Jenkinson C, Kennedy S. The impact of endometriosis upon quality of life: a qualitative analysis. J 
Psychosom Obstet Gynaecol 2004;25:123-33. 
3. 
Peveler R, Edwards J, Daddow J, Thomas E. Psychosocial factors and chronic pelvic pain: a comparison of 
women with endometriosis and with unexplained pain. J Psychosom Res 1996;40:305-15. 
4. 
Desrochers G, Bergeron S, Khalifé S, Dupuis M-J, Jodoin M. Fear avoidance and self-efficacy in relation to 
pain and sexual impairment in women with provoked vestibulodynia. Clin J Pain 2009;25:520-7. 
5. 
Peters KM, Killinger KA, Carrico DJ, Ibrahim IA, Diokno AC, Graziottin A. Sexual function and sexual distress 
in women with interstitial cystitis: a case-control study. Urology 2007;70:543-7. 
6. 
Turk DC, Swanson KS, Tunks ER. Psychological approaches in the treatment of chronic pain patients--when 
pills, scalpels, and needles are not enough. Can J Psychiatry 2008;53:213-23. 
7. 
Ford AC, Talley NJ, Schoenfeld PS, Quigley EMM, Moayyedi P. Efficacy of antidepressants and 
psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut 2009;58:367-78. 
8. 
Masheb RM, Kerns RD, Lozano C, Minkin MJ, Richman S. A randomized clinical trial for women with 
vulvodynia: Cognitive-behavioral therapy vs. supportive psychotherapy. Pain 2009;141:31-40. 
9. 
Blodt S, Pach D, Eisenhart-Rothe SV, et al. Effectiveness of app-based self-acupressure for women with 
menstrual pain compared to usual care: a randomized pragmatic trial. Am J Obstet Gynecol 2018;218:227 e1- e9. 
10. 
Gonçalves AV, Barros NF, Bahamondes L. The Practice of Hatha Yoga for the Treatment of Pain Associated 
with Endometriosis. J Altern Complement Med 2017;23:45-52. 
11. 
Saxena R, Gupta M, Shankar N, Jain S, Saxena A. Effects of yogic intervention on pain scores and quality of 
life in females with chronic pelvic pain. Int J Yoga 2017;10:9-15. 
12. 
Busch AJ, Webber SC, Richards RS, et al. Resistance exercise training for fibromyalgia. Cochrane Database 
Syst Rev 2013;12:CD010884. 
13. 
Hayden JA, van Tulder MW, Malmivaara A, Koes BW. Exercise therapy for treatment of non-specific low 
back pain. Cochrane Database Syst Rev 2005:CD000335. 
14. 
Johannesson E, Simrén M, Strid H, Bajor A, Sadik R. Physical activity improves symptoms in irritable bowel 
syndrome: a randomized controlled trial. Am J Gastroenterol 2011;106:915-22. 
15. 
Mist SD, Jones KD. Randomized Controlled Trial of Acupuncture for Women with Fibromyalgia: Group 
Acupuncture with Traditional Chinese Medicine Diagnosis-Based Point Selection. Pain Med 2018. 
16. 
Hsieh LL, Kuo CH, Lee LH, Yen AM, Chien KL, Chen TH. Treatment of low back pain by acupressure and 
physical therapy: randomised controlled trial. BMJ 2006;332:696-700. 

Novel web-based, self-directed intervention for chronic pelvic pain 
Version v.19_irb  
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10 July 2024 
 
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17. 
Eccleston C, Fisher E, Craig L, Duggan GB, Rosser BA, Keogh E. Psychological therapies (Internet-delivered) 
for the management of chronic pain in adults.  Cochrane Database of Systematic Reviews2014. 
18. 
Williams AC, Eccleston C, Morley S. Psychological therapies for the management of chronic pain 
(excluding headache) in adults. Cochrane Database Syst Rev 2012;11:CD007407. 
19. 
Williams DA, Cary MA, Groner KH, et al. Improving physical functional status in patients with fibromyalgia: 
a brief cognitive behavioral intervention. J Rheumatol 2002;29:1280-6. 
20. 
Smeets RJEM, Vlaeyen JWS, Kester ADM, Knottnerus JA. Reduction of pain catastrophizing mediates the 
outcome of both physical and cognitive-behavioral treatment in chronic low back pain. J Pain 2006;7:261-71. 
21. 
van Lankveld JJDM, ter Kuile MM, de Groot HE, Melles R, Nefs J, Zandbergen M. Cognitive-behavioral 
therapy for women with lifelong vaginismus: a randomized waiting-list controlled trial of efficacy. J Consult Clin 
Psychol 2006;74:168-78. 
22. 
Johannesson E, Ringström G, Abrahamsson H, Sadik R. Intervention to increase physical activity in irritable 
bowel syndrome shows long-term positive effects. World J Gastroenterol 2015;21:600-8. 
23. 
Bazarganipour F, Taghavi SA, Allan H, et al. A randomized controlled clinical trial evaluating quality of life 
when using a simple acupressure protocol in women with primary dysmenorrhea. Complement Ther Med 
2017;34:10-5. 
24. 
Geneen LJ, Moore RA, Clarke C, Martin D, Colvin LA, Smith BH. Physical activity and exercise for chronic 
pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev 2017;4:CD011279. 
25. 
van Koulil S, van Lankveld W, Kraaimaat FW, et al. Tailored cognitive-behavioral therapy and exercise 
training for high-risk patients with fibromyalgia. Arthritis Care Res 2010;62:1377-85. 
26. 
Meissner K, Schweizer-Arau A, Limmer A, et al. Psychotherapy With Somatosensory Stimulation for 
Endometriosis-Associated Pain. Obstetrics & Gynecology 2016;128:1134-42. 
27. 
Lemstra M, Olszynski WP. The effectiveness of multidisciplinary rehabilitation in the treatment of 
fibromyalgia: a randomized controlled trial. Clin J Pain 2005;21:166-74. 
28. 
Moore RA, Derry S, McQuay HJ, et al. Clinical effectiveness: an approach to clinical trial design more 
relevant to clinical practice, acknowledging the importance of individual differences. Pain 2010;149:173-6.