Partners for Pain & Wellbeing Equity: A Randomized Trial of Community Supported Complementary and Integrative Health Self-management for Back Pain
Phase: NA
Conditions: Neck Pain, Low Back Pain, Chronic Pain
Sponsor: University of Minnesota

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PRP Study Protocol V5 October 2023 
 
STUDY PROTOCOL 
 
PARTNERS FOR PAIN & WELLBEING EQUITY:  
A RANDOMIZED TRIAL OF COMMUNITY SUPPORTED 
COMPLEMENTARY AND INTEGRATIVE HEALTH  
SELF-MANAGEMENT FOR BACK PAIN  
 
 
National Clinical Trial (NCT) Identified Number:  NCT05786508 
 
Principal Investigators: Roni Evans, DC, MS, PhD & Brent Leininger, DC, MS, PhD 
Integrative Health & Wellbeing Research Program  
Earl E. Bakken Center for Spirituality & Healing 
C504 Mayo Memorial Building, University of Minnesota 
420 Delaware Street S.E. 
Minneapolis, MN, USA 55455 
 
 
Grant Number: 1R61AT012309 
 
Funded by: The National Center for Complementary and Integrative Health through the 
National Institutes of Health’s Helping End Addiction Long Term (HEAL) Initiative 
 
Version Number:  5  
 
October 23 2023 
 
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document constitutes agreement by the recipient that no unpublished information contained 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.  
 
 
 
 
 
 
 

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PRP Study Protocol V5 October 2023 
PROTOCOL REVISION HISTORY 
 
Protocol 
Version # 
Revision 
Date 
Summary of Changes 
Protocol Section(s) 
2 
May 2023 
Updated non-key personnel: Removed Jennifer Walter 
3. Study Roster 
2 
May 2023 
Clarified study is conducted in English and 
supplementary materials are available in Spanish for 
individuals with English as a second language 
9.2 Inclusion Criteria 
2 
May 2023 
Added details about the use of TransportationPlus, a 
rideshare program that will be used to transport 
participants to study visits to address a potential barrier 
to participation. 
9.4.5 Retention Strategies 
9.4.6 Strategies for Addressing 
Barriers to Recruitment & 
Retention of Populations Who 
Experience Health Disparities 
2 
May 2023 
Changed minimum group size from 10 to 7 
11.1 Intervention Overview 
2 
May 2023 
Updated screening activities and clarified the timing 
between randomization and the start of the group 
interventions is up to 28 days. Also clarified the timing 
for follow up assessments (Month 2 for the R61 and 
Months 2, 4, and 6 for the R33) is from the start of the 
group interventions.  
13.2 Screening Assessments 
13.3 Intervention Sessions 
13.4 Follow up Assessments 
2 
May 2023 
Included video presentation of study and timing for 
when it would be sent to potential participants 
16.1.2 Consent Procedures and 
Documentation 
3 
July 2023 
Added the following questionnaires: Perceived 
Discrimination in Healthcare and an adapted version to 
assess Perceived Discrimination in the P4P Study.  
 
13.1 Schedule of Assessments 
13.2.3 Baseline Two Screen 
14.2.3 Implementation & Disparity 
Mitigating Outcomes 
 
3 
July 2023 
Updated non-key personnel: Added Emma Ward, 
Shraddha Bika, Jake Kremer, and Erika Kennedy; 
removed Aditi Das. 
3. Study Roster 
4 
August 
2023 
Updated sample size (n=30-60) from (n=30-40). 
Response to recruitment initiatives has gone very well. 
Study team wanted to provide additional opportunity 
for underserved participants to be included in the 
study. Funds and resources are in place for up to 60 
participants.   
4.1 Synopsis 
6 Study Procedures 
10.1 Enrollment Procedures 
15.2.1 R61 Randomized Pilot Study 
4 
August 
2023 
Removed Gaye Adams Massey from External Co-
Investigator Consultants (no access to participants or 
identified data). 
3 Study Roster 
5 
October 
2023 
Added Carmen Robles, Ivette Izea-Martinez, Jamiela 
Taylor (no access to participants or identified data). 
Added section for former team members and listed past 
project personal: Kari Davis BA, Aditi Das MPH, and Gaye 
Adams Massey, JD. 
Updated credentials for project team 
3 Study Roster 
 
 
 

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PRP Study Protocol V5 October 2023 
TABLE OF CONTENTS 
 
1 
Statement of Compliance ....................................................................................................... 9 
2 
Investigator Signatures ......................................................................................................... 10 
3 
Study Roster .......................................................................................................................... 11 
4 
Protocol Summary ................................................................................................................ 16 
4.1 
Synopsis .......................................................................................................................... 16 
4.2 
Study Overview .............................................................................................................. 18 
4.3 
Participating Sites ........................................................................................................... 19 
5 
Introduction .......................................................................................................................... 20 
5.1 
Background..................................................................................................................... 20 
6 
Study Objectives ................................................................................................................... 23 
6.1 
R61 Aims & Transition Milestones ................................................................................. 23 
6.2 
R33 Aims ......................................................................................................................... 25 
7 
Risk/Benefit Assessment ....................................................................................................... 25 
7.1 
Overview of Risk/Benefit................................................................................................ 25 
7.2 
Benefits........................................................................................................................... 25 
7.2.1 
Quality Improvement Activities (R61/R33) ............................................................. 26 
7.2.2 
Randomized Pilot Study (R61) & Randomized Trial (R33) ...................................... 26 
7.3 
Risks ................................................................................................................................ 26 
7.3.1 
Quality Improvement Activities (R61, R33) ............................................................ 26 
7.3.2 
Randomized Pilot Study (R61) & Randomized Trial (R33) ...................................... 26 
7.4 
Risk Mitigation ................................................................................................................ 27 
8 
Study Design.......................................................................................................................... 28 
8.1 
Overall Design ................................................................................................................ 28 
8.2 
Study Rationale .............................................................................................................. 28 
8.3 
Underlying Models & Frameworks ................................................................................ 29 
9 
Study Population ................................................................................................................... 30 
9.1 
Study Population Definitions.......................................................................................... 30 
9.2 
Inclusion Criteria ............................................................................................................ 30 
9.3 
Exclusion Criteria ............................................................................................................ 31 
9.4 
Recruitment & Retention ............................................................................................... 32 

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PRP Study Protocol V5 October 2023 
9.4.1 
Recruitment Process ............................................................................................... 32 
9.4.2 
Source & Identification of Potential Participants ................................................... 32 
9.4.3 
Recruitment Materials ............................................................................................ 33 
9.4.4 
Payment .................................................................................................................. 33 
9.4.5 
Retention Strategies ............................................................................................... 33 
9.4.6 
Strategies For Adressing Barriers to Recruitment & Retention of Populations who 
Experience Health Disparities (PEHD) ................................................................................... 34 
10 
Enrollment Procedures ...................................................................................................... 35 
10.1 
Number of Study Participants .................................................................................... 35 
10.2 
Screening & Enrollment .............................................................................................. 35 
10.3 
Randomization & Blinding .......................................................................................... 35 
11 
Interventions ...................................................................................................................... 35 
11.1 
Intervention Overview ................................................................................................ 35 
11.2 
Experimental Intervention (Partners4Pain) ............................................................... 36 
11.3 
Control Intervention (Keys to Wellbeing) ................................................................... 37 
11.4 
Intervention Fidelity ................................................................................................... 37 
11.5 
Intervention Adherence ............................................................................................. 37 
11.6 
Concomitant Therapy ................................................................................................. 38 
11.7 
Rescue Therapy........................................................................................................... 38 
12 
Intervention Discontinuation & Participant Withdrawal ................................................... 38 
12.1 
Discontinuation of Study Intervention ....................................................................... 38 
12.2 
Participant Withdrawal from Study ............................................................................ 39 
12.3 
Lost to Follow-up ........................................................................................................ 39 
13 
Study Assessments & Procedures ...................................................................................... 40 
13.1 
Schedule of Assessments............................................................................................ 40 
13.2 
Screening Assessments ............................................................................................... 41 
13.2.1 
Initial Screen ........................................................................................................ 41 
13.2.2 
Baseline One Screen ............................................................................................ 41 
13.2.3 
Baseline Two Screen............................................................................................ 41 
13.3 
Intervention Sessions ................................................................................................. 42 
13.4 
Follow-up Assessments .............................................................................................. 42 
13.5 
Adverse Events & Serious Adverse Events ................................................................. 42 
13.5.1 
Definition of Adverse Events ............................................................................... 42 

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PRP Study Protocol V5 October 2023 
13.5.2 
Definition of Serious Adverse Events .................................................................. 42 
13.5.3 
Classification of an Adverse Event ...................................................................... 43 
13.5.4 
Relationship to Study Procedures ....................................................................... 43 
13.5.5 
Expectedness ....................................................................................................... 43 
13.5.6 
Time Period & Frequency for Event Assessment & Follow-up ........................... 44 
13.5.7 
Adverse Event & Serious Adverse Event Reporting ............................................ 44 
13.5.8 
Events of Special Interest .................................................................................... 45 
13.5.9 
Reporting of Pregnancy ....................................................................................... 45 
13.6 
Unanticipated Problems ............................................................................................. 45 
13.6.1 
Unanticipated Problems Reporting ..................................................................... 46 
14 
Outcomes ........................................................................................................................... 46 
14.1 
R61 Outcomes ............................................................................................................ 46 
14.1.1 
VIEWS AND OPINIONS ......................................................................................... 47 
14.1.2 
Feasibility Outcomes ........................................................................................... 48 
14.2 
R33 Randomized Hybrid Effectiveness-Implementation Trial ................................... 49 
14.2.1 
Primary Effectiveness Outcome .......................................................................... 49 
14.2.2 
Secondary Effectiveness Outcomes .................................................................... 50 
14.2.3 
Implementation & Disparity Mitigating Outcomes ............................................. 51 
15 
Statistical Considerations ................................................................................................... 51 
15.1 
Hypotheses ................................................................................................................. 52 
15.2 
Sample Size ................................................................................................................. 52 
15.2.1 
R61 Randomized Pilot Study ............................................................................... 52 
15.2.2 
R33 Randomized Hybrid Effectiveness-Implementation Trial ............................ 52 
15.3 
Populations for Analyses & General Approach (R33) ................................................. 53 
15.4 
Data Analyses ............................................................................................................. 53 
15.4.1 
R61 Phase ............................................................................................................ 53 
15.4.2 
R33 Randomized Hybrid Effectiveness-Implementation Trial ............................ 54 
16 
Regulatory, Ethical, & Study Oversight .............................................................................. 55 
16.1 
Informed Consent ....................................................................................................... 55 
16.1.1 
Consent & Other Informational Documents ....................................................... 55 
16.1.2 
Consent Procedures & Documentation .............................................................. 56 
16.2 
Study Discontinuation & Closure ................................................................................ 57 
16.3 
Confidentiality & Privacy ............................................................................................ 58 

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PRP Study Protocol V5 October 2023 
16.4 
Key Roles & Study Governance .................................................................................. 59 
16.5 
Safety Oversight.......................................................................................................... 62 
16.6 
Clinical Monitoring ..................................................................................................... 62 
16.7 
Quality Assurance & Quality Control .......................................................................... 63 
16.8 
Data Handling & Record Keeping ............................................................................... 63 
16.8.1 
Data Collection & Management Responsibilities ................................................ 63 
16.8.2 
Study Records Retention ..................................................................................... 64 
16.9 
Protocol Deviations .................................................................................................... 64 
16.10 
Publication & Data Sharing Policy .............................................................................. 65 
16.11 
Conflict of Interest Policy ........................................................................................... 66 
16.12 
Future Use of Data ...................................................................................................... 67 
17 
References ......................................................................................................................... 67 
 
 
TABLES APPEARING IN THE PROTOCOL 
 
Table 1. CIH Self-Management Strategies for Back Pain .............................................................. 22 
Table 2. Risks According to Study Phase and Aims ....................................................................... 25 
Table 3. Models and Frameworks Used in Project ....................................................................... 29 
Table 4. Study Population Definitions and Nature of Participation ............................................. 30 
Table 5. TIDieR Intervention Elements Common to Both Groups ................................................ 36 
Table 6. Schedule of Assessments for Study Participants** (R61 Randomized Pilot Study and 
R33 Randomized Trial) .................................................................................................................. 40 
Table 7. Relationship of Adverse Events to Study Procedures ..................................................... 43 
Table 8. Reporting for Adverse events, Serious adverse events, and Other events .................... 44 
Table 9.  Schedule of Quality Improvement Data Collection........................................................ 47 
Table 10. Key Roles and Study Governance .................................................................................. 60 
 
 
 

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PRP Study Protocol V5 October 2023 
ABBREVIATIONS/DEFINITIONS 
ADL 
 
 
Activities of Daily Living  
AE  
 
 
Adverse Event 
APEASE  
 
Affordability, Practicality, Effectiveness, Adaptability, Safety, Equity 
BL  
 
 
Baseline 
BP  
 
 
Back pain conditions including back or neck pain 
BP-PEHD    
 
Back pain from populations that experience health disparities 
BPS  
 
 
Biophysical, psychological and social 
CC 
 
 
Creative commons 
CIH  
 
 
Complementary and Integrative Healthcare 
Co-I  
 
 
Co-Investigator 
CoC 
 
 
Certificate of Confidentiality 
COI  
 
 
Conflict of Interest 
COM-B  
 
Capability, Opportunity, Motivation - Behavior 
ConNECT 
Integrating CONtext; Fostering a Norm of Inclusion; Ensuring Equitable Diffusion 
of Innovations; Harnessing Communication Technology; Prioritizing Specialized 
Training 
CRF    
 
 
Code of Federal Regulations 
CRF  
 
 
Case report form 
CV 
 
 
Curriculum Vitae 
DC    
 
 
Doctor of Chiropractic 
DSMP   
 
Data Safety and Monitoring Plan 
ETHOS   
 
Ethical Oversight Submission System 
FFR  
 
 
Federal Financial Report 
GAD 
 
 
Generalized Anxiety Disorder 
GCP     
 
Good Clinical Practice 
HEAL   
 
Helping End Addiction Long Term 
HHS  
 
 
Health and Human Services 
HIPAA  
 
Health Insurance Portability and Accountability Act 
HSR  
 
 
Human Subjects Research 
HST  
 
 
Health Sciences Technology 
ICF  
 
 
Informed Consent Form 
ICH      
 
International Council on Harmonization 
ID 
 
 
Identification 
IHWRP  
 
Integrative Health and Wellbeing Research Program 
IMC  
 
 
Independent Monitoring Committee 
IRB 
 
 
Institutional Review Board 
LAR 
 
 
Legally Authorized Representative 
LBP  
 
 
Low back Pain 
MN 
 
 
Minnesota 
MMSE  
 
Mini-Mental Status Examination 
MOP 
 
 
Manual of Operations 
MS    
 
 
Master of Science 
NCCIH   
 
National Center for Complementary and Integrative Health 
NCT 
 
 
National Clinical Trial 
NIH      
 
National Institutes of Health 
NP  
 
 
Neck Pain 

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PRP Study Protocol V5 October 2023 
OHRP  
 
Office for Human Research Protections 
OIC  
 
 
Office of Institutional Compliance 
P&A  
 
 
Professional & Administrative 
PEG  
 
 
Pain, Enjoyment of Life and General Activity 
PEHD  
 
Populations Experiencing Health Disparities 
PGIC 
 
 
Patient Global Impression of Change 
PhD     
 
Doctor of Philosophy 
PHQ-2  
 
Patient Health Questionnaire-2 
PI  
 
 
Principal Investigator 
PO  
 
 
Program Officer 
PROMIS 
 
Patient-Reported Outcome Measurement Information System 
RE-AIM  
 
Reach, Effectiveness, Adoption, Implementation, Maintenance 
REDCap  
 
Research Electronic Data Capture 
REPA   
 
Report of External Professional Activities 
RNI  
 
 
Report of New Information 
SAE  
 
 
Serious Adverse Event 
SARP 
 
 
Study Accrual and Retention Plan 
SPH 
 
 
School of Public Health 
SRQ 
 
 
Self-Report Questionnaire 
TAPS 
 
 
Tobacco, Alcohol, Prescription medications and other susbtances 
TIDieR  
 
Template for implementation for intervention description and replication  
UMN   
 
University of Minnesota 
UPIRTSO  
 
Unanticipated Problem Involving Risks to Subjects of Others 
UROC  
 
Robert J. Jones Urban Research and Outreach-Engagement Center 
USA 
 
 
United States of America 
US    
 
 
United States 
VA 
 
 
Veterans Administration 
YMCA  
 
Young Men’s Christian Association 
YWCA  
 
Young Women’s Christian Association 
 
 

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PRP Study Protocol V5 October 2023 
1 STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonization Good Clinical 
Practice (ICH GCP) and the following:  
 
• 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).  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible 
for the conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form(s) 
must be obtained before any participant is consented. Any amendment to the protocol will require 
review and approval by the IRB 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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

10 
PRP Study Protocol V5 October 2023 
2 INVESTIGATOR SIGNATURES  
 
The signatures 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 Signature:                                                            
Date 10/23/2023 
Name: Roni Evans DC, MS, PhD 
Title: Director and Associate Professor 
Affiliation:  Integrative Health & Wellbeing Research Program, Earl E. Bakken Center for Spirituality & 
Healing, University of Minnesota 
Telephone: 612-626-6477 
Email: evans972@umn.edu 
 
Principal Investigator Signature:                                                 
Date 10/23/2023 
Name: Brent Leininger DC, MS, PhD 
Title: Assistant Professor 
Affiliation:  Integrative Health & Wellbeing Research Program, Earl E. Bakken Center for Spirituality & 
Healing, University of Minnesota 
Telephone: 612-626-6477 
Email: lein0122@umn.edu 
 
 
 
 
 
 
 
 
 
 

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PRP Study Protocol V5 October 2023 
3 STUDY ROSTER  
 
KEY PERSONNEL 
 
University of Minnesota Investigators 
 
Roni Evans, DC, MS, PhD 
Co-Principal Investigator  
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: evans972@umn.edu 
 
Brent Leininger, DC, MS, PhD 
Co-Principal Investigator 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: lein0122@umn.edu 
 
Robin Austin, MS, DC, DNP, PhD 
Co-Investigator  
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: quis0026@umn.edu 
 
Gert Bronfort, DC, PhD 
Co-Investigator  
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: bronf003@umn.edu 
 
Alex Haley, JD, MBA 
Co-Investigator 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: haley045@umn.edu 
 
Linda Hanson, DC, MS 
Co-Investigator 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: hans4236@umn.edu 
 

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PRP Study Protocol V5 October 2023 
Douglas Kennedy, MA, PhD 
Co-Investigator 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: dougk@umn.edu 
 
Craig Schulz, DC, MS 
Co-Investigator  
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: schu1385@umn.edu 
 
Julian Wolfson, PhD 
Co-Investigator 
Data Collection/Management 
University of Minnesota, School of Public Health 
420 Delaware Street SE, Minneapolis, MN 55414 
Email: julianw@umn.edu 
 
Diana Burgess, PhD 
Co-Investigator 
University of Minnesota, Department of Medicine 
401 East River Parkway, Minneapolis, MN 55414 
Email: tuch0007@umn.edu 
& 
US Department of Veterans Affairs, Center for Care Delivery and Outcomes Research 
2E-102 One Veterans Drive, Minneapolis MN 55417 
Email: Diana.Burgess@va.gov and  
 
External Co-Investigator Consultants* 
*No access to study data or participants 
 
Eric Roseen, DC, MSc 
Co-Investigator Consultant 
Boston University, School of Medicine 
85 East Newton Street, Room 1020, Boston MA 02118 
Email: ericjroseen@gmail.com  
 
Hedy Lemar Walls, MBA, EDd 
Co-Investigator Consultant 
YMCA of the North 
651 Nicollet Mall, Street2: Suite 500, Minneapolis MN 55402 
Email: Hedy.Walls@ymcamn.org 
 
NON-KEY PERSONNEL 
Research Staff – University of Minnesota 

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PRP Study Protocol V5 October 2023 
Oliver Ang, PT, MCISc, DSc 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: ang00005@umn.edu 
 
Shraddha Bika, PT 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: bika0010@umn.edu 
 
John Jodzio, BA 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (612) 301-9006 
Email: jodz0001@umn.edu 
 
Erika Kennedy, BA 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: kenne693@umn.edu 
 
Jake Kremer, DPT 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: krem0081@umn.edu 
 
Amy McGarness, BA 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: mcgar128@umn.edu 
 
Don Thorpe, DC, MS 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: thorp167@umn.edu 
 
Blong Vang, DC 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: leex0298@umn.edu  

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PRP Study Protocol V5 October 2023 
 
Emma Ward, BS 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: ward1190@umn.edu 
 
Lynn Winkel, DC 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: lwinkel@umn.edu 
 
Consultants* 
*No access to study data or participants 
 
Merrie Benasutti BA, MSEd 
University of Minnesota, Office for Public Engagement 
110 Morrill Hall, 100 Church St. SE, Minneapolis, MN 55455 
Email: benas021@umn.edu  
 
Ronda Chakolis PharmD, MPH 
MN State Board of Pharmacy 
Prime Therapeutics 
Email: rchakolis@gmail.com 
 
Clarence Jones M.Ed, CPH, CHW, CPE 
Hue-MAN Partnership 
Email: clarencejones7428@gmail.com 
 
 
Robin Hedrick MA, NBC-HWC 
YMCA of the North 
651 Nicollet Mall, Street2: Suite 500, Minneapolis MN 55402 
Email: robin.hedrick@ymcamn.org  
 
Nawal Hirsi BS 
Fairview Health Services, Community Advancement, Community Program & Initiatives 
Email: Nawal.Hirsi@fairview.org 
 
Ivette Izea-Martinez  
YWCA of St. Paul 
Email: IIzeaMartinez@ywcastpaul.org 
 
Mallory Mahaffey MPH, LADC 
VA Minnesota 
Email: mahaf016@umn.edu 
 

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PRP Study Protocol V5 October 2023 
Heidi Mendenhall MS, DC, DACBR 
Northwestern Health Sciences University 
2501 W 84th St, Bloomington, MN 55431 
Email: hmendenh@umn.edu 
 
Carmen Robles 
78 10th St E Unit 906, St Paul, MN 55101 
Email: afrolatino.news@yahoo.com 
 
Sam Simmons LADC 
Samuel Simmons Consulting 
3033 27th Ave S, P.O. Box 6120, Minneapolis, MN 55406 
Email: ssc@comcast.net 
 
Jamiela Taylor, BA 
NorthPoint Health & Wellness Center 
1256 Penn Avenue North, Suite 5300 Minneapolis, MN 55411 
Email: jtaylor@npimn.org 
 
Bruce Yang BS 
YMCA of the North 
651 Nicollet Mall, Street2: Suite 500, Minneapolis MN 55402 
Email: bruce.l.yang@gmail.com 
 
Makeda Zulu MPA 
University of Minnesota 
Robert J. Jones Urban Research and Outreach-Engagement Center 
Email: zulug001@umn.edu 
 
 
Past Project Personal  
 
Aditi Das, MPH  
University of Minnesota 
Email: dasxx125@umn.edu 
 
Kari Davis 
Make a Wish Minnesota 
Email: kdavis@mn.wish.org  
 
Gaye Adams Massey, JD 
Co-Investigator Consultant 
YMCA St. Paul 
375 Selby Ave, St. Paul MN 55102 
Email: GAMassey@ywcastpaul.org 
 
 

16 
PRP Study Protocol V5 October 2023 
 
4 PROTOCOL SUMMARY 
 
4.1 SYNOPSIS 
 
The following provides a synopsis for the R61 (Phase I) of the project. 
 
Title 
Phase I (R61): Partners for Pain & Wellbeing Equity: A Randomized Trial of Community 
Supported Complementary and Integrative Health Self-Management for Back Pain 
Grant Number 
1R61AT012309 
Study Description 
The focus of the R61 project is on developing and optimizing community-based 
programs for the self-management of back or neck pain for individuals from 
populations that experience health disparities (BP-PEHD). We will use a community-
engaged research approach to conduct quality improvement activities that involves 
gathering feedback from multiple stakeholders to inform development of the study 
interventions and materials which will be followed by a randomized pilot study of 30 
to 60 participants to evaluate feasibility.  
Objectives/Aims 
Aim 1: We will use mixed methods data collection from multiple levels of stakeholders 
to assess barriers and facilitators to participating in back pain self-management, and 
community supported programs. 
Aim 2. Based on information gathered in Aim 1, we will perform participatory 
intervention mapping to co-develop a community supported CIH self-management 
intervention program (and control) for BP-PEHD. 
Aim 3. We will conduct a feasibility study (n=30 to 60) to assess essential scientific and 
feasibility milestones including: 
a) Finalizing and securing agreements, and regulatory approvals (IRB, NCCIH, 
IMC) for all required protocols and plans (e.g., clinical protocol, Data Safety 
and Monitoring Plan, Study Accrual and Retention Plan, etc.)  
b) Recruiting and enrolling individuals with BP-PEHD and measuring recruitment 
rates, enrollment rates 
c) Delivering experimental and control interventions and measuring 
intervention adherence and fidelity rates 
d) Data collection by assessing follow up rates of future trial outcome measures 
as well as the usability and functionality of data collection systems 
e) Stakeholder views of barriers and facilitators to the above, including 
affordability, practicality, effectiveness, acceptability, safety, and equity and 
other factors that could affect the future full scale trial’s success  
Endpoints 
Aim 1: Needs and perspectives for addressing barriers and facilitators to back pain 
management and participation in community supported CIH programs 
 
Aim 2: Reactions and opinions to Aim 1 findings and planned resources and 
approaches for the CIH self-management program and feasibility study 
 
Aim 3: Recruitment feasibility, enrollment feasibility, intervention acceptability and 
credibility, intervention fidelity, and data collection feasibility 
Study 
Populations 
Aims 1-3: Community Stakeholders defined as Community Partner Organization 
leadership members; Community Facilitators; and other Community Members for 
whom BP-PEHD is relevant  
 

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PRP Study Protocol V5 October 2023 
Aim 3: 30 to 60 adults with chronic neck or back pain from populations that 
experience health disparities due to race/ethnicity or socioeconomic status 
Phase/Design 
Mixed methods quality improvement (Aims 1, 2) leading to randomized pilot study 
(Aim 3) 
Sites/Facilities 
University of Minnesota; Community Partners include the YMCA of the North and 
YWCA St. Paul 
Study 
Interventions 
(experimental, 
control) 
Both intervention programs include nine, 90-minute group sessions that occur weekly.  
Experimental: Partners4Pain is a self-management program of evidence based 
complementary and integrative health approaches for pain including pain education, 
mindfulness, cognitive behavioral approaches, and neck/back specific exercises. 
 
Active Control: Keys to Wellbeing is a general health and wellbeing education program 
addressing topics such as keeping socially connected, finding meaning and purpose, 
addressing mental health, and keeping physically fit. The program was designed to 
control for time, attention, and many other key contextual factors (e.g., program 
format, materials). 
Duration 
Planning, preparation phase (Aims 1, 2): Nine months 
Randomized pilot study (Aim 3): One year 
Participant 
Duration 
Randomized pilot study: Three months 
 
The following provides a synopsis for the future R33 (Phase II) of the project.  
 
Title 
Phase II (R33): Partners for Pain & Wellbeing Equity: A Randomized Trial of 
Community Supported Complementary and Integrative Health Self-Management for 
Back Pain 
Grant Number 
TBD 
Study Description 
The R33 project focuses on assessing the effectiveness of a community-based back or 
neck pain self-management program, Partners4Pain, relative to an active control for 
improving important outcomes impacted by chronic pain (Aim 1), and the impact of 
health disparity factors (Aim 2). The project also focuses on gathering feedback as 
part of quality improvement activities to gain a better understanding of factors 
(including those that might mitigate disparities) that could affect the long-term 
implementation of the community-based self-management programs (Aim 3). 
Objectives/Aims 
Aim 1: To assess the relative effectiveness of Partners4Pain versus Keys to Wellbeing 
in terms of: 
a) Primary effectiveness outcomes of pain intensity and interference over 6 months 
using bi-monthly assessments 
b) Secondary effectiveness outcomes of pain impact, self-efficacy and other HEAL 
outcomes 
 
Aim 2: To assess the impact of health disparity factors on the effectiveness of 
Partners4Pain for primary and secondary outcomes through subgroup analyses which 
account for potential complexities between disparity factors 
 
Aim 3: To describe important disparity mitigating and implementation related 
measures that can impact and inform sustained translation of the program with 
community partner organizations 
Endpoints 
Aims 1-2: Pain intensity and interference; pain impact; self-efficacy; life satisfaction; 
physical functioning; pain catastrophizing; interoceptive awareness; satisfaction; 

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PRP Study Protocol V5 October 2023 
improvement; medication use; participation in social roles; healthcare use; CIH self-
management; sleep; depression; anxiety; substance use; adverse events 
 
Aim 3: Views on barriers/facilitators to participation, effectiveness, adoption, 
maintenance/sustainability, resource needs; Views on affordability, practicality, 
effectiveness, acceptability, safety, and equity of educational programs; Ability of 
programs to meet capability, opportunity, and motivational related needs; Views on 
inclusion and cultural sensitivity; Views on the community-researcher relationship; 
Views on alignment with organizational mission and business models  
Study Populations 
Aims 1-3: 376 adults with chronic neck or back pain from populations that experience 
health disparities due to race/ethnicity or socioeconomic status 
 
Aim 3: Community Stakeholders defined as Community Partner Organization 
leadership members; Community Facilitators; and other Community Members for 
whom BP-PEHD is relevant 
Phase/Design 
Phase II randomized hybrid effectiveness implementation trial using individual level 
randomization and group treatments (Aims 1, 2); quality improvement activities to 
gather and account for stakeholder feedback (Aim 3). 
Sites/Facilities 
University of Minnesota; Community Partners include the YMCA of the North and 
YWCA St. Paul  
Study 
Interventions 
(experimental, 
control) 
Both intervention programs include nine, 90-minute group sessions that occur 
weekly.  
Experimental: Partners4Pain is a self-management program of evidence based 
complementary and integrative health approaches for pain including pain education, 
mindfulness, cognitive behavioral approaches, and neck/back specific exercises. 
 
Active Control: Keys to Wellbeing is a general health and wellbeing education 
program addressing topics such as keeping socially connected, finding meaning and 
purpose, addressing mental health, and keeping physically fit. The program was 
designed to control for time, attention, and other key contextual factors (e.g., 
program format, materials). 
Duration 
Three years 
Participant 
Duration 
Seven months 
 
 
4.2 STUDY OVERVIEW 
 
This research is part of a two-phase project (R61/R33) supported through the National Institutes of 
Health’s Helping to End Addiction Long-term (HEAL) Initiative. The project is summarized below and in 
Figure 1. 
 
R61 Overview. The R61 Phase focuses on planning and preparation related ‘quality improvement 
activities’ (R61 Aims 1-2) that will assess community stakeholder needs and optimize study interventions 
and approaches. A randomized pilot study (R61 Aim 3) will evaluate feasibility and provide another 
opportunity for ‘quality improvement’ activities and provide refinements in preparation for the R33. The 
interventions are Partners4Pain (experimental), comprised of evidence based Complementary and 
Integrative Health (CIH) modalities (e.g., pain education, mindfulness, cognitive behavioral approaches, 
exercises and physical activity) and an active control, Keys to Wellbeing. Both programs will leverage 

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assets (e.g., content videos, workbooks, etc.) developed and successfully applied by the investigators in 
previous studies; these will be used as a starting point to develop and optimize the programs for 
individuals with BP-PEHD.1-10 Both intervention programs consist of weekly 90-minute group sessions for 
9 weeks that will be offered in-person and via videoconference depending on community partner 
organization and participant needs.  
 
R33 Overview. The R33 Phase includes a randomized hybrid effectiveness implementation trial (Aims 1 
and 2) to evaluate the effectiveness of the Partners4Pain intervention compared to the Key to Wellbeing 
active control intervention and the impact on health disparities related to pain management. The R33 
will also engage study participants and community stakeholders in ‘quality improvement activities’ (R33 
Aim 3) that assess their views of barriers and facilitators to long-term implementation of the 
Partners4Pain intervention in community-based settings, including those that may help mitigate 
disparities.  
 
 
 
4.3 PARTICIPATING SITES 
 
University of Minnesota Research Sites 
The University of Minnesota Twin Cities serves as the primary research site and will assume the 
following responsibilities: 
• 
Designing and developing the protocol, manual of operations, informed consent and case report 
forms 
• 
Collecting and maintaining critical regulatory documents from affiliated investigators, e.g., 
resume/CV, certification of completion of training, signed COI disclosure forms, delegation of 
authority logs 

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PRP Study Protocol V5 October 2023 
• 
Storing and/or managing data, performing data analysis, and data monitoring activities 
• 
Ensuring informed consent is obtained and documented from each subject in compliance with 
federal regulations 
• 
Recruiting, screening, and enrolling participants 
• 
Delivering study interventions 
• 
Protecting participants’ rights  
• 
Providing study specific training to research personnel  
• 
Developing and coordinating randomization scheme and process  
• 
Monitoring compliance with protocol and tracking deviations from the study protocol 
• 
Ensuring the correct versions of the protocol and consent documents are used 
• 
Tracking, reporting, and maintaining documentation of all serious adverse events and 
unanticipated problems and disseminating the information to appropriate oversight boards 
• 
Providing periodic updates to affiliated investigators on subject enrollment, general study 
progress, and relevant scientific advances  
• 
Developing the data flow and data management procedures, including data entry, error 
identification, and correction  
• 
AE monitoring and reporting 
• 
Implementing and monitoring quality control procedures  
• 
Generating and disseminating reports (e.g., enrollment, AEs, participant status, site 
performance, quality control) 
• 
Comply with necessary protocols and maintain consistency with the HEAL Initiatives Public 
Access and Data Sharing Policy 
• 
Maintaining documentation of IRB approvals and correspondence and communicating study 
status changes 
 
 
Participating University of Minnesota Sites for the R61 are: 
Robert J. Jones Urban Research and Outreach-Engagement Center 
2001 Plymouth Ave, Minneapolis, MN 55411 
Phone: 612-626-UROC (8762) 
Website: https://uroc.umn.edu/ 
 
Community Partner Organization Sites: Leaders from the YMCA of the North, the YWCA St. Paul, and 
the Hue-MAN Partnership serve as consultants on this project. Their role is limited to sharing views and 
opinions about barriers and facilitators to the study interventions and other processes and procedures, 
as well as disseminating information about the project through their routine communication channels. 
Leaders from Community Partner Organizations will facilitate the use of space at their affiliated 
locations for the University of Minnesota research staff to conduct research procedures (e.g., screening, 
intervention sessions). None of the Community Partners (including their employees) will take part in 
study activities involving human subjects nor will they have access to study data.  
5  INTRODUCTION 
 
5.1 BACKGROUND 
 

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Disease prevalence and impact. Back pain (BP) conditions, including low back and neck pain, are among 
the most common and disabling chronic pain disorders in the U.S.11-14 and a leading cause of disability 
worldwide.15,16 An estimated 40-80% of adults experience low back pain (LBP) or neck pain (NP), and 
almost one third of all Americans experience chronic NP or LBP at some point in their lives.11,17-20 BP is 
the most common reason for seeking care in the healthcare system21,22 and the U.S. spends more on BP 
than any other condition. In 2016, roughly 10% of healthcare expenditures ($134.5 billion) were devoted 
to the care of BP.23 BP like most health conditions, has become widely recognized as more than a 
physical phenomenon; it is a complex condition influenced by interrelated biophysical, psychological, 
and social (BPS) factors.24,25 
 
Population. This study focuses on individuals with back pain from populations who experience health 
disparities (BP-PEHD). Overall, there has been relatively little research examining BP-PEHD. While BP 
prevalence rates are similar between White and Black Americans, Black Americans are more negatively 
impacted with higher severity and disability.26 
 
Current Back Pain Management. While BP has become widely recognized as a biophysical, psychological 
and social condition, current BP management is still mainly biophysically oriented and the majority of 
cases remain poorly treated27,28 with a heavy emphasis on symptom management29,30 that fails to 
address sufferers’ needs.24,29-31 The use of epidural injections, opioid prescriptions, and spinal surgeries 
has increased at alarming rates over the past few decades, with little positive impact on patient 
outcomes.32-35 Of particular concern is the overreliance on opioids, which are used by an estimated 30% 
of chronic LBP patients and 15% of all NP patients.36,37  While these more aggressive treatments are 
appropriate for some individuals, the majority of individuals with BP would benefit from less invasive 
approaches that foster engagement in adaptive pain behaviors, including self-management.30,38,39 
 
Disparities in BP care and management are also evident. A study of older U.S. adults seeking care for BP 
found Blacks and Hispanics used less health care and also had less improvement in clinical outcomes 
relative to Whites.40 The opioid epidemic has hit low-income White communities the hardest, where 
opioid prescriptions and deaths due to overdose are most prevalent.41 While Black Americans are less 
likely to be prescribed opioids for BP42,43 they are also more likely to be under-assessed and under-
treated in many areas including screening, diagnostic imaging, use of physical therapy, and surgery.44 
Additionally, adults who are Black, Hispanic, or have lower educational attainment, income, insurance 
coverage and self-reported health, are less likely to use complementary and integrative health (CIH) 
approaches, for which there is a growing evidence base.45 
 
Socioeconomic Factors and Health Disparities. The relationships between socioeconomic factors and 
health disparities in the United States are complex due to long-standing institutional discrimination and 
structural racism.46,47 There is evidence that socioeconomic factors (e.g., income, employment status, 
home ownership) are associated with greater likelihood of chronic pain and poorer outcomes.48-50 Lack 
of social support51-53 and work related factors such as physical workload, education, injury 
compensation, and dissatisfaction can also have a negative effect on BP.54 Drawing from the larger pain 
field, poor quality relationships and social stressors (e.g., due to racism, ostracism, injustice, invalidation, 
isolation, etc.) also contribute to poor outcomes.55,56 To move the BP-PEHD research field forward, it is 
imperative that social contexts are more intentionally considered and taken into account in the research 
process. 
 
Improved Pain Management. To reduce the burden of BP, individuals require greater access to evidence 
based care that addresses their biopsychosocial needs.57 There has been a growing recognition that BP, 

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much like other chronic health conditions, requires ongoing attention to lifestyle factors and 
engagement in effective self-management.30,38 While patients recognize the need for self-management 
strategies, they often need support and validation to initiate and maintain optimal self-care.58,59 This 
isn’t surprising given that BP is frequently associated with psychological risk factors including poor 
cognitive and emotional coping strategies, depression, catastrophizing, and fear avoidance beliefs, 
which can make self-management difficult.54,60 
 
Self-Management. While definitions of self-management interventions vary considerably, they can be 
generally defined as structured or semi-structured instructional programs, which include multiple, 
distinct modalities aimed at promoting active involvement in managing one’s condition.38,39  Given the 
symptomatic nature of pain, and the fact that it is encountered throughout the lifespan, pain self-
management can be viewed as a foundational behavioral skill that all could benefit from. Commonly, 
self-management approaches help individuals learn and adopt a set of healthy behaviors (e.g., activity 
versus inactivity, socialization versus isolation, non-drug symptom management versus substance 
reliance). For BP, there is a range of CIH self-management modalities including psychological strategies 
(e.g., behavioral or cognitive); mind-body approaches (including relaxation, meditation or guided 
imagery); physical activity (e.g., general and rehabilitative exercise, yoga, tai chi); lifestyle advice (e.g., 
for sleep, daily activities, social support); and pain education (e.g., pain theories, prognosis, and pain 
management tips).39,45 Importantly, there is research evidence to support all of these CIH self-
management strategies for BP (see Table 1). 
 
Table 1. CIH Self-Management Strategies for Back Pain 
Strategy 
Evidence of effectiveness 
Pain education 
Small effects on pain and function61,62 
Cognitive behavioral/coping strategies 
(including progressive muscle relaxation and 
guided imagery)  
Small effects on pain and function63 
Mindfulness based interventions 
Small effects on pain, small to no effect on function63-65 
Exercise (back specific and general) 
Moderate effects on pain, small effects on function63,66 
 
Whole Person CIH Self-Management. There has been a growing number of multi-modality CIH self-
management programs that address pain from a whole person perspective (e.g., taking into account BPS 
factors).67-69 In our current research, pain sufferers and community stakeholders have expressed an 
interest in and need for such an approach (R33AT00911, R34AT011209-01S1). One of the most studied 
existing pain self-management programs is the widely adopted Stanford Program which addresses pain 
from a more holistic perspective. It is comprised of lay person-led sessions including pain education, 
effective communication, mind-body approaches (e.g., relaxation), and general exercise for strength, 
flexibility, etc.70 Research suggests this program, and those similar to it, can lead to improved pain and 
health behaviors, self-efficacy, and overall health.67,71 Effect sizes are modest however, and the research 
is limited by inattention to underlying theoretical frameworks that align individuals’ specific BP related 
needs with appropriate program elements; further, there has been a lack of consideration of key issues 
which may contribute to health disparities such as affordability, practicality, acceptability, safety, and 
equity.38,67,71,72 A major limitation of the existing research of multi-modality CIH self-management 
programs is that most of the study populations have been mainly female, White, highly educated, with 
good self-reported health67,71 and thus of questionable generalizability to PEHD. 

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Overcoming Barriers to BP CIH Self-Management. The impact of self-management programs on 
reducing disparities for pain, including BP, has rarely been addressed73,74 and much of the CIH self-
management research has under-represented individuals who are socio-economically disadvantaged or 
have a race and ethnicity other than non-Hispanic White.71,75 There are a range of socioeconomic 
barriers that prevent individuals with BP-PEHD from receiving and engaging in CIH self-management 
programs. This includes geography, cost, insurance, time, and other factors.76-79 Further, there are 
additional barriers to engaging PEHD in research including fear, distrust, and poorly developed 
relationships between researchers and communities.80-82 All of these hurdles, if not addressed, lead to 
continued unequal access to BP care among marginalized groups, perpetuating health disparities.73 
 
Community Based Programs which exist outside the costly and overburdened health care system have 
the opportunity to overcome many of these barriers, especially if they include delivery formats that are 
feasible for community organizations to sustain. For example, programs focused on other chronic 
diseases, like the Diabetes Prevention Program, have demonstrated promise in having lay facilitators 
implement standardized group programs in community-based settings, including YMCAs.83 Recent work 
by the investigators has also demonstrated it is feasible to deliver self-management programs in person 
or via telehealth (e.g., videoconferencing) with staff facilitators in YMCA and non-clinical VA settings 
(R33AT00911, NH170001). There is still much work to be done however, including greater community 
stakeholder involvement - earlier, more frequently, and more collaboratively - throughout the research 
process,80 especially in the BP and CIH fields.10,84 Such efforts, including needs assessment, attention to 
cultural tailoring, and involvement of community facilitators, have shown promise for improving BP 
knowledge, self-management skills, and general health.74 This is consistent with what is advocated in the 
community engagement research fields80 and warrants greater attention in future CIH self-management 
research for BP-PEHD.10,84,85 
 
6 STUDY OBJECTIVES 
 
Our broad long-term objective is to bolster the widespread implementation of evidence based CIH 
approaches for individuals with back pain from populations that experience health disparities (BP-
PEHD). The project utilizes mixed methods and will occur over two phases (R61/R33, see Figure 1).  
 
6.1 R61 AIMS & TRANSITION MILESTONES 
 
Phase I (R61). We will conduct the necessary planning and preparations leading to a randomized 
feasibility study including co-development and assessment of Partners4Pain, a self-management 
program comprised of evidence based CIH approaches (e.g., pain education, mindfulness, cognitive 
behavioral/pain coping strategies, back specific exercise) and Keys to Wellbeing (e.g., general health 
education and exercise). 
 
R61 Aim 1. We will use mixed methods data collection from multiple levels of stakeholders to assess 
barriers and facilitators to participating in BP self-management and community supported programs. 
This data collection will augment the existing literature and the results of previous and ongoing studies 
by the investigators.  

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PRP Study Protocol V5 October 2023 
R61 Aim 2. Based on information gathered in R61 Aim 1, we will perform participatory intervention 
mapping to co-develop a community supported CIH self-management intervention program (and 
control) for BP-PEHD. 
R61 Aim 3. We will conduct a feasibility study (n=30 to 60) to assess essential scientific and feasibility 
milestones including: 
a. Finalizing and securing agreements and regulatory approvals (IRB, NCCIH, IMC) for all required 
protocols and plans (e.g., clinical protocol, Data Safety and Monitoring Plan, Study Accrual and 
Retention Plan, etc.) 
b. Recruiting and enrolling individuals with BP-PEHD and measuring recruitment and enrollment rates 
c. Delivering experimental and control interventions and measuring intervention adherence and fidelity 
rates 
d. Data collection by assessing follow up rates of future trial outcome measures as well as the usability 
and functionality of data collection systems 
e. Stakeholder views of barriers and facilitators to the above, including affordability, practicality, 
effectiveness, acceptability, safety, and equity and other factors that could affect the future full scale 
trial’s success 
 
The following specific transition milestones have been approved by the funder (NCCIH). 
• 
Demonstrate the ability to recruit and retain subjects in the clinical study as follows: 
o 
Randomize at least 30 participants 
o 
75% or more of randomized participants are from NIH-defined racial/ethnic 
health disparity groups 
o 
80% or more of randomized participants are retained for primary outcome 
measurement at the end of the R61 study (2 month follow up) regardless of 
adherence to the intervention 
• 
Demonstrate that the delivery of the intervention(s) and the control intervention(s) 
under study can be delivered consistently, as defined by: 
o 
85% or more of randomized participants engage in 1 or more sessions 
o 
75% or more of randomized participants engage in at least 6 of 9 sessions 
• 
Demonstrate the safety and tolerability of the intervention(s) used in the study by: 
o 
5% or less of randomized participants experience a severe or serious adverse 
event related to the intervention(s) 
o 
75% or more of randomized participants attend at least 6 of 9 sessions 
o 
75% or more of randomized participants are satisfied with assigned program 
• 
Demonstrate the fidelity of the intervention(s) used in the study by: 
o 
Program facilitators deliver 90% of session activities 90% of the time 
• 
Demonstrate the ability to collect study data by: 
o 
80% or more of randomized participants complete follow up at 2 months (end 
of the R61 study) 
• 
Prior to submission of the written R33 transition request, submit R33 clinical study 
protocols and Data and Safety Monitoring Plan to NCCIH for review and approval  
o 
Submit the R33 clinical DSMP and SARP by the end of month 20 
o 
Submit a written R33 Transition Request by the end of month 21 
 
All the above milestones must be reached before requesting transition to the R33 phase.  
 

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6.2 R33 AIMS 
 
Phase II (R33). Upon approval by the funder of transition milestones (see above), we will conduct a full-
scale multi-level randomized hybrid effectiveness implementation trial (n=376) of the community 
supported CIH self-management program, Partners4Pain, compared to the active control, Keys to 
Wellbeing, both of which will have been optimized and feasibility tested in Phase I. 
 
R33 AIM 1. To assess the relative effectiveness of Partners4Pain versus Keys to Wellbeing in terms of: 
a. Primary effectiveness outcomes of pain intensity and interference over 6 months using bi-monthly 
assessments 
b. Secondary effectiveness outcomes of pain impact, self-efficacy and other HEAL outcomes. 
R33 AIM 2. To assess the impact of health disparity factors on the effectiveness of Partners4Pain for 
primary and secondary outcomes through subgroup analyses which account for potential complexities 
between disparity factors 
R33 AIM 3. To describe important disparity mitigating and implementation related measures that can 
impact and inform sustained translation of the program with community partner organizations 
 
7 RISK/BENEFIT ASSESSMENT 
 
7.1 OVERVIEW OF RISK/BENEFIT 
 
The risks differ across study phases and aims; these are summarized in Table 2 and Section 7.3. 
 
Table 2. Risks According to Study Phase and Aims 
Study Phase (Aims) 
Approach 
(Population) 
Risks 
Risk Level 
Phase I (R61 Aims 1, 2) 
Quality Improvement 
Activities (Community 
Stakeholders) 
Breach of Confidentiality 
Minimal 
Phase I (R61 Aim 3) 
Randomized Pilot 
Study 
(Study Participants 
with Back Pain) 
Breach of Confidentiality 
Completing Health Surveys 
Group Based Behavioral Interventions 
Natural History of Pain 
Low 
Phase II (R33 Aims 1-3)  
Randomized Hybrid 
Effectiveness-
Implementation Trial 
(Study Participants 
with Back Pain) 
Breach of Confidentiality 
Completing Health Surveys 
Group Based Behavioral Interventions 
Natural History of Pain 
Low 
Phase II (R33 Aim 3) 
Quality Improvement 
Activities 
(Community 
Stakeholders) 
Breach of Confidentiality 
Minimal 
 
7.2 BENEFITS 
 

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7.2.1 QUALITY IMPROVEMENT ACTIVITIES (R61/R33) 
 
The benefits to stakeholders taking part in the Quality Improvement Activities (R61, R33) include 
experiencing satisfaction in contributing views and opinions that may help individuals with BP-PEHD. 
 
7.2.2 RANDOMIZED PILOT STUDY (R61) & RANDOMIZED TRIAL (R33) 
 
The benefits to participants of the Randomized Pilot Study (R61) and Randomized Trial (R33) include: 
• 
Learning new information about pain and ways to take care of it 
• 
Learning new information about overall health and wellbeing 
• 
Experiencing health benefits, including decreased stress and increased wellbeing 
• 
Experiencing improvement in pain symptoms 
• 
Experiencing improvement in the ability to do daily activities 
 
7.3 RISKS 
 
7.3.1 QUALITY IMPROVEMENT ACTIVITIES (R61, R33) 
 
The risks to stakeholders taking part in the Quality Improvement Activities (R61, R33) are considered 
minimal.  
• 
Breach of Confidentiality.  
o New information will be gathered from stakeholders regarding their views and opinions 
about the study interventions and approaches. This information is not anticipated to place 
individuals at risk of criminal or civil liability or be damaging to the subjects’ financial 
standing, employability, educational advancement, or reputation.  
o Secondary research data will also be used, including non-identifiable data from previous IRB 
approved studies.  
 
7.3.2 RANDOMIZED PILOT STUDY (R61) & RANDOMIZED TRIAL (R33) 
 
The risks to participants of the Randomized Pilot Study (R61) and Randomized Trial (R33) are considered 
low.  
• 
Breach of Confidentiality.  
o New information will be gathered from participants and is not anticipated to place 
individuals at risk of criminal or civil liability or be damaging to the subjects’ financial 
standing, employability, educational advancement, or reputation.  
• 
Completing Health Surveys. Participants will be asked to complete health surveys as part of the 
screening and follow up data collection; they may feel uncomfortable answering questions they 
feel are too personal.  
• 
Taking Part in Group Based Behavioral Interventions. Participants will be asked to take part in 
group behavioral interventions (via Zoom or in-person); the interventions are not physically 

27 
PRP Study Protocol V5 October 2023 
invasive, embarrassing, or offensive, and not expected to have adverse lasting impact. Some 
participants may experience some anxiety or nervousness when participating in group activities. 
o Partners4Pain (Experimental Intervention).  Risks associated with the experimental 
behavioral intervention may occur in program sessions and practicing on one’s own. 
Expected risks are mild short-lasting physical discomfort (e.g., muscle and joint soreness) as 
a result of performing short periods of back-specific and general exercises (~5-15 minutes); 
participants might also feel emotional when doing the brief mind-body practices (~5 
minutes) which include mindfulness and behavioral coping strategies (e.g., relaxed 
breathing, guided imagery, progressive muscle relaxation).  
o Keys to Wellbeing (active control intervention). Risks associated with the active control 
intervention may occur in program sessions and practicing on one’s own. Expected risks are 
mild short-lasting physical discomfort (e.g., muscle and joint soreness) as a result of 
performing short periods of general exercises; participants might also feel emotional when 
doing the brief workbook exercises (~5 minutes) that ask them to reflect on different areas 
of their health and wellbeing.  
• 
Natural History of Pain. People with back and neck pain that is chronic in nature often 
experience fluctuations in pain severity, location, character, and quality; such fluctuations may 
be study related (e.g., due to engaging in exercises) or unrelated (e.g., aggravated by lifting at 
work or home).  
 
7.4 RISK MITIGATION 
 
The following describes how risks will be minimized. 
 
• 
Breach of Confidentiality: All staff will complete UMN required training on HIPAA, data safety, 
and the Responsible Conduct of Research prior to working on the project. Data will be stored 
and accessed following UMN policies for data privacy and confidentiality (SEE SECTION 16.3). 
Identifiable data will be stored on password protected and HIPAA compliant databases and will 
only be accessed using HST (Health Sciences Technology) issued and maintained computers. All 
identifiable data will be removed from datasets used for analysis and all published reports will 
be summary in nature with no identifiable information for individual participants. Secondary 
research data from completed and ongoing studies will be limited to summarized findings from 
reports without identifiable information for individual participants. 
• 
Completing Health Surveys: We will provide an explanation for why we are asking questions 
that may be considered personal and allow participants the ability to not answer any question 
they don’t feel comfortable answering.  
• 
Taking Part in Group Based Behavioral Interventions: The behavioral interventions include 
activities and exercises that are suitable for a range of abilities and preferences. Participants will 
also have the ability to refrain from participating in activities that feel uncomfortable. Program 
facilitators will be trained and certified by investigators and monitored for fidelity to ensure they 
are implementing the interventions in a manner that optimizes patient safety. This will include 
how to monitor for potential emotional or physical discomfort during session activities and how 
to implement safety protocols if needed. All participants will be encouraged to contact the 
project coordinator or an investigator regarding any side effects or adverse events that occur. 
Participants who experience a potential adverse event will be contacted by a study team 
member to ensure safety protocols are followed and gather information for adverse event 

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PRP Study Protocol V5 October 2023 
reporting. Adverse events impacting participant safety may result in withdrawal from the study 
intervention. 
• 
Natural History of Pain: We will provide information to participants about the natural history of 
pain and how to manage fluctuations. They will also be encouraged to contact their healthcare 
provider regarding exacerbations in pain they find troubling or hard to manage. Participants will 
have no restrictions on the care they can receive for their back or neck pain.  
 
8 STUDY DESIGN 
 
8.1 OVERALL DESIGN  
 
This is a two-phase project (see Figure 1). 
 
Phase I (R61) includes mixed methods quality improvement activities and a randomized pilot study. 
Phase II (R33) includes a mixed methods randomized hybrid effectiveness-implementation trial and 
mixed methods quality improvement activities.  
 
8.2 STUDY RATIONALE 
 
Rationale for Community Engaged Approach: 
There are several barriers to participating in research that have been identified in our own and others’ 
work, especially among those from PEHD.82,86-89 This includes distrust in researchers and the research 
process, lack of awareness and knowledge of research, and logistical obstacles including time, location, 
and others.82,90 Further, while there is evidence to support several CIH self-management approaches for 
BP, the research to date has rarely taken the needs and preferences of individuals with BP-PEHD into 
account.26,91-93 Thus, an important aspect of this project is to use an iterative community engaged and 
participatory research approach to gather views and opinions from multiple levels of community 
stakeholders through mixed methods quality improvement processes. This will provide more specific 
information regarding the needs of individuals with BP-PEHD than what is currently available in the 
literature and will provide an opportunity to co-develop solutions which is a critical aspect of community 
engaged research.80 
 
Rationale for Experimental Intervention: The Partners4Pain program was chosen as the experimental 
intervention based on the literature supporting the effectiveness and safety of the individual CIH self-
management approaches (see Table 1) of which it is comprised. There has been very little research to 
date that has investigated the combination of evidence-based CIH approaches, especially in community-
based settings and for individuals with BP-PEHD. As a consequence, it is important to assess the 
feasibility of a combined CIH intervention; the extent to which it meets participants’ needs can be 
implemented within community partner organizations in a fashion that facilitates long term adoption. 
 
Rationale for Control Intervention: The Keys to Wellbeing program controls for contextual factors 
including time, attention, delivery format, and intervention materials (workbooks, videos). The rationale 
for the choice of comparison intervention is based on feedback from community partners and our 
Community Advisory Team. They have expressed a desire for interventions that are useful to 
participants (versus a no-treatment control), especially given the distrust in research among individuals 

29 
PRP Study Protocol V5 October 2023 
with BP-PEHD, noted above. Previous studies conducted by our group have also found the Keys to 
Wellbeing Program to be satisfying to participants and something they are willing to engage in. We have 
also observed differences in outcomes between the Keys control intervention and other CIH 
experimental intervention. We have not assessed it however in populations with BP-PHED. Thus, it is 
important to assess the feasibility of the control intervention in individuals with BP-PEHD.  
 
8.3 UNDERLYING MODELS & FRAMEWORKS 
 
Engaging communities in CIH research for BP is inherently complex and requires established models and 
frameworks to guide the work.24,30,94 Our team has developed a comprehensive conceptual approach for 
the proposed project based on insights from our community partners, experience of the investigators, 
and the scientific literature (see Introduction). It is informed by complementary models appropriate for 
addressing the project goal of developing and implementing evidence based CIH interventions to 
mitigate BP related health disparities (see Table 3).  
 
Table 3. Models and Frameworks Used in Project 
Framework or 
Model 
Rationale for use 
Application in Project 
RE-AIM 
Framework95 
Provides overarching guidance for ensuring 
relevant contextual factors that can impact 
study implementation and translation, are 
considered throughout the project lifespan 
 
Shapes ‘quality improvement 
activities’ and ‘disparity 
mitigating’ measures of reach, 
effectiveness, adoption, 
implementation and 
maintenance; informs ‘quality 
improvement analyses’ 
ConNECT 
Framework80 
Ensures greater and sustained consideration to 
how the researchers work with communities 
who experience health disparities. Includes 
guiding attention to social contexts; fostering 
norms of inclusion; ensuring equitable diffusion 
of innovations; harnessing communication 
technology; and prioritizing community 
engagement training for study team members 
Shapes conduct of entire 
project and informs ‘quality 
improvement analyses’ 
Dynamic 
Biopsychosocial 
Model96 
Facilitates consideration of the complex 
reciprocal interactions between the evolving 
biopsychological person with BP and their 
external, social environment. This is essential for 
providing insights into pain sufferers’ whole-
person needs, and BPS risk and protective 
factors that may serve as barriers and 
facilitators to BP-PEHD engagement in self-
management72 
Informs the 
design/development of the 
intervention and choice of 
outcome measures; informs 
‘quality improvement analyses’ 
COM-B model72 
A comprehensive behavioral model that 
provides guidance for assessing and addressing 
an individual’s capability, opportunity, and 
motivational needs to achieve desired 
Informs the ‘quality 
improvement analyses’ that 
help identify individuals’ needs; 
informs the design/ 

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PRP Study Protocol V5 October 2023 
behavioral outcomes; considers affordability, 
practicality, effectiveness/cost-effectiveness, 
acceptability, safety, and equity 
development of intervention by 
matching needs to specific 
intervention strategies 
 
9 STUDY POPULATION 
 
9.1 STUDY POPULATION DEFINITIONS 
 
Community engaged research and implementation designs require multiple levels of participation in a 
range of study activities (see Figure 1). Study population definitions are summarized below in Table 4. 
 
Table 4. Study Population Definitions and Nature of Participation 
Population 
Definition 
Nature of Participation (e.g. Study 
Activity, Aim) 
Community 
Stakeholders 
Individuals from local communities whose 
participation is limited to sharing views and 
opinions of barriers/facilitators to interventions, 
study approaches 
 
INCLUDE: 
Community Members: Individuals from 
populations who experience health disparities 
(PEHD) who have experiences dealing with pain 
themselves or helping others in pain who are from 
PEHD (e.g., caregivers, clinicians, etc.)  
 
Community Facilitators: Individuals who currently 
facilitate or could facilitate similar intervention 
programs as to what is being examined in the 
project 
 
Community Partner Organization Leadership: 
Individuals in leadership positions at Community 
Partner Organizations (YMCA of the North, YWCA 
St. Paul, Hue-MAN Partnership) 
R61 Quality Improvement Activities 
(Aims 1-3) 
 
R33 Quality Improvement Activities 
(Aim 3) 
Study Participants 
Individuals with back pain from populations who 
experience health disparities (BP-PEHD) and meet 
inclusion criteria for Randomized Pilot Study (R61) 
or future Randomized Hybrid Effectiveness-
Implementation Trial 
R61 Randomized Pilot Study  
(Aim 3) 
 
R33 Randomized Hybrid 
Effectiveness Trial (Aims 1-3) 
 
 
9.2 INCLUSION CRITERIA 
 
The following inclusion criteria apply to the R61 Randomized Pilot Study and the R33 Randomized Hybrid 
Effectiveness-Implementation Trial. 

31 
PRP Study Protocol V5 October 2023 
 
1. Provide a signed and dated informed consent form 
2. State willingness to comply with all study procedures outlined in the consent form  
3. Be 18 years of age or older 
4. Have self-reported chronic back pain (defined as pain in the low or mid back, or neck pain) which 
has lasted for 3 months or longer 
5. Have a score of 3 or higher on the self-reported Pain, Enjoyment of Life and General Activity (PEG) 
scale (0 to 10) 
6. Be a member of one or more of the following NIH-designated health disparity populations:* 
a. American Indian/Alaska Native 
b. Asian 
c. Black/African American 
d. Hispanic/Latino 
e. Native Hawaiian/Pacific Islanders 
f. Socioeconomically disadvantaged (annual household income less than $50,000) 
 
*This project focuses on back pain in populations that experience health disparities (BP-PEHD). These 
populations are underrepresented in research studies, have less access to resources for the 
management of back pain, and have poorer outcomes (see Section 5, Introduction). The study is offered 
in English, but supplementary materials are available in Spanish for individuals where English is a second 
language. Supplementary materials may also be offered in other languages. 
 
9.3 EXCLUSION CRITERIA 
 
The following exclusion criteria apply to the R61 Randomized Pilot Study and the R33 Randomized 
Hybrid Effectiveness-Implementation Trial. 
 
1. Hospitalization for severe mental illness in past six months because the mindfulness and behavioral 
mind-body practices (e.g., meditation, progressive muscle relaxation, etc.) in the experimental 
intervention may aggravate symptoms of severe mental illness 
2. Active psychotic symptoms, suicidal ideation, or manic episodes in the past three months for the 
same reasons noted in #1 
3. Self-reported cancer with active treatment involving radiation or chemotherapy due to the potential 
for complications of their back or neck pain and impact on health outcomes 
4. Dementia – Mini Mental State Exam score of 23 or lower for those with suspicion of cognitive 
impairment due to safety risks (e.g., not being able to follow directions for safe physical exercise) 
5. Self-reported pregnancy due to the fact that back pain is often associated with pregnancy and 
differs from non-pregnancy related back pain and thus might have different impacts on health 
outcomes 
6. Children under the age of 18* 
 
*Children under the age of 18 will be excluded from the proposed project consistent with NIH Policy and 
Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects 
(http://grants.nih.gov/grants/guide/notice-files/not98-024.html). A separate age-appropriate study for 
children is preferable for several reasons. Most importantly, the self-management education programs 
are directed toward adults, with content, activities, and exercises that may not be suitable for children. 
Further, interventions are provided in group settings with facilitated discussions geared towards 

32 
PRP Study Protocol V5 October 2023 
challenges faced by adults with back pain. Adapting both the experimental and control interventions for 
children would require substantial modification, so much so that a separate study is warranted. In 
addition, many of the biopsychosocial outcome measures proposed for the project were developed 
specifically for adult populations and have unknown validity or reliability in younger populations. 
 
9.4 RECRUITMENT & RETENTION 
 
Potential Community Stakeholders for the R61 and R33 Quality Improvement Activities will be identified 
through the routine communication channels of our Community Partnership Organizations (e.g., system-
wide emails, newsletters, organizational meetings, presentations, etc.). 
 
Study Participants (See Section 9.1 Study Population Definitions) for the R61 Randomized Pilot Study and 
the R33 Randomized Hybrid Effectiveness-Implementation Trial will be identified as described below.  
 
9.4.1 RECRUITMENT PROCESS 
 
A range of recruitment strategies will be used to recruit Study Participants; these will be initiated 
approximately 3-6 months prior to screening activities and will continue until enrollment is complete. 
These include: 
● Dissemination of print and digital recruitment materials via routine communication channels 
(emails, newsletters, etc.) through our Community Partner Organizations and other Community 
Members 
● Giving study and health related presentations in the community to raise awareness about the study 
● Participating in local community events (e.g., health fairs) where dissemination of recruitment 
materials is encouraged 
● Using paid advertising (e.g., digital, print, and radio ads) in local media outlets with reach to PEHD 
● Listing study on ResearchMatch, an electronic volunteer recruitment registry  
● Distributing print and digital flyers and post-cards on UMN campuses and in the community 
● Including information about the study in UMN affiliated newsletters (e.g., The Center for Spirituality 
& Healing, Office of Public Engagement, the Urban Research and Outreach-Engagement Center 
(UROC), etc.) 
● Posting information about the study on UMN affiliated social media (e.g., The Center for Spirituality 
& Healing and UROC Facebook and Twitter accounts) and websites (e.g., the School of Nursing, the 
Center for Spirituality & Healing, as well as a unique study landing page) 
● Sharing information about the study with other study investigators who have mechanisms in place 
to query individuals during the consent process regarding their interest in being contacted about 
additional studies  
 
9.4.2 SOURCE & IDENTIFICATION OF POTENTIAL PARTICIPANTS 
 
Potential Study Participants will self-identify by responding to recruitment strategies and materials 
within the general public. We will NOT access private/protected records (e.g., electronic medical 
records) to identify potential participants. 

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PRP Study Protocol V5 October 2023 
 
9.4.3 RECRUITMENT MATERIALS 
 
Recruitment materials will include emails, newsletter study summaries, digital and print media 
advertisements, radio advertisements, ResearchMatch study description, print and digital flyers, print 
post cards, social media posts and advertisements, and a website. Copies of these materials will be 
submitted in ETHOS for approval prior to their use. 
9.4.4 PAYMENT 
 
Study Participants in the R61 Randomized Pilot Study and the R33 Randomized Hybrid Effectiveness-
Implementation Trial will be provided compensation for their time participating in research activities 
using a pre-paid debit card called Greenphire ClinCard. Study participants will be compensated for the 
following study activities: 
• 
$20 for each baseline screening visit attended ($40 total) 
• 
$30 for each of the educational program sessions attended ($270 total) 
• 
$20 for each follow-up assessment completed ($20 total in R61; $60 total in R33) 
 
Total potential compensation for study participants will be $330 during the R61 and $370 during the 
R33. 
 
Community Stakeholders participating in formal interviews and focus groups will be compensated $30 
per event. Community stakeholders named as consultants for the project will be compensated using 
agreed upon consultancy fees and processes. 
 
9.4.5 RETENTION STRATEGIES 
 
There are many well-recognized barriers to research participation overall including inconvenience, time 
commitment, geographic location, etc. The investigators have decades of experience successfully 
addressing these challenges. We will implement the following strategies used in previous studies to 
facilitate study participant engagement in the interventions and data collection: 
● Research staff will routinely track all study visits/time points per participant (screening and 
intervention session, follow-up) and will work closely with the Community Facilitators and 
Community Coordinators to devise timely solutions for mitigating retention issues.  
● We will offer a range of program session times to accommodate participants’ needs; this 
includes early mornings, day, and evenings. Saturday appointments are also an option, as 
needed. Programs will be offered in different formats (in-person, videoconference) with our 
host Community Partner Organizations to accommodate participant preferences and needs.  
● If participants need to miss a program session, they will be able to view intervention session 
educational and skill videos by accessing the study website.  
● All participants will be provided reminders of their study related visits.  
● Participants will be provided detailed instructions on how to find Community Partner 
Organization sites for in-person visits; transportation instructions including bus, train, and 

34 
PRP Study Protocol V5 October 2023 
interstate routes will be included. Free, easily accessible parking will be made available to study 
participants.  
● Transportation services to and from study visits will be provided to participants, as needed, 
using Transportation Plus, a Twin Cities based company. The study team will arrange taxi 
services for the participant. Prior to initiating the ride, participants will provide verbal consent to 
have their contact information (e.g., name, address, phone number) shared with Transportation 
Plus. Verbal consent will be captured in the study record. Transportation is paid for by the study; 
participants will not incur out of pocket costs.  
● Participants will receive regular reminders (automated via text, email, or other methods 
depending on participant preference) to complete self-report questionnaires (SRQs). Study staff 
will closely monitor completion and contact participants if not completed within designated 
time frames.  
● During screening, study staff will provide a detailed description of the study, including what 
participants can expect with respect to the commitment necessary to preserve the integrity of 
the project prior to enrollment. Participants will be given as much time as needed to decide if 
they want to participate.  
● The research team will use patient-centered communication to foster trusting relationships 
between the study staff and participants. If challenges arise with participants, the study team 
(e.g., study coordinators) will talk openly with participants about these challenges, without 
pressure. Further, study staff will make efforts to keep in touch with study participants using 
participants' preferred contact (e.g., email, phone call), especially after completion of the 9-
week intervention phase, to facilitate follow up.  
 
 
9.4.6 STRATEGIES FOR ADRESSING BARRIERS TO RECRUITMENT & RETENTION OF 
POPULATIONS WHO EXPERIENCE HEALTH DISPARITIES (PEHD) 
 
• 
To improve researchers’ cultural competency, the research team are provided dedicated 
professional time to engage in ongoing professional development with Community Partner 
Organizations, including the YMCA of the North’s Equity Innovation Center. 
• 
To address the mistrust individuals from PEHD may have in the research process, we will: 
o Work with Community Partner Organizations and Community Champions to serve as 
trusted messengers to raise awareness about the project 
o Continue to encourage and support ongoing research staff participation in community 
volunteer activities and events 
o Hire Community Coordinators in consultation with our Community Partner 
Organizations to facilitate interfacing with community members 
o Work with an established Community Advisory Team which is guided by a Team Charter, 
with clearly defined roles and processes for collaborative decision making 
o Provide equitable compensation for Community Advisory Team Members, Community 
Consultants, Community Coordinators, Community Stakeholders, and Study Participants 
• 
To address logistical issues, including access to technology, we will work with Community 
Partner Organizations to conduct study activities at sites located in and/or easily accessible to 
communities of color and lower socioeconomic status. In addition, we will provide access to 
transportation services for study participants to attend study visits. 

35 
PRP Study Protocol V5 October 2023 
• 
To address the need to be responsive to community needs, we will involve Community 
Stakeholders, the Community Advisory Team, and our Community Partner Organizations across 
the research process. 
 
10 ENROLLMENT PROCEDURES 
 
10.1 
NUMBER OF STUDY PARTICIPANTS 
 
A total of 30-60 individuals will be enrolled for the R61 Randomized Pilot Study; 376 will be enrolled for 
the R33 Randomized Hybrid Effectiveness-Implementation Trial. 
10.2 
SCREENING & ENROLLMENT 
 
Screening and enrollment for the R61 Randomized Pilot Study and the R33 Randomized Hybrid 
Effectiveness-Implementation Trial will take place over three events. Potential participants will be 
initially screened for basic eligibility criteria using a web-based survey that can be completed online or 
over the phone with study staff. Interested and eligible individuals will be invited to a baseline 1 
screening visit which will occur face-to-face either in person or using videoconferencing technology. 
Participants who are eligible will attend a baseline 2 screening visit conducted either face-to-face or over 
the phone. Eligible participants will be enrolled in the study at the conclusion of baseline 2 (also see 
Schedule of Assessments and Sections 13.1 to 13.4 for specific details regarding activities at each visit). 
10.3 
RANDOMIZATION & BLINDING 
 
Eligible individuals will be enrolled and randomized using blocked randomization (with varying block 
sizes) following stratification for session offerings (e.g., Summer 2023 - Saturday mornings). Computer 
generated random treatment assignments will be prepared by the independent study statistician and 
conveyed electronically through REDCap (the electronic study database) at the time of enrollment to 
preserve allocation concealment. All study staff responsible for screening and enrollment procedures 
will be blinded to upcoming treatment assignments. The Co-PIs, select Co-Investigators, and the study 
statistician will be blinded until the study database is locked for analysis. The Co-PIs are authorized to be 
unblinded when needed for safety-related processes (e.g., decisions to withdraw participants from the 
intervention following adverse events). 
11 INTERVENTIONS 
 
11.1 
INTERVENTION OVERVIEW 
 
Both the experimental (Partners4Pain) and active control (Keys to Wellbeing) interventions will be 
informed by the work conducted in R61 Aims 1 and 2 and research done previously by the investigators 
(R33AT009110, NH170001, UH3AT008769, R34AT011209).1-10 The Template for Intervention Description 
and Replication (TIDieR) checklist has been and will continue to be used to guide the description of the 
study interventions97 to facilitate future results interpretation, as well as dissemination and replication. 
Consistent with the RE-AIM and ConNECT frameworks guiding this project, we anticipate the 
interventions will be further shaped and adapted based on stakeholder feedback to meet the needs of 

36 
PRP Study Protocol V5 October 2023 
community stakeholders and those with BP-PEHD, based on information gathered in R61 Aims 1 and 
2.80,95,98 Elements common to the experimental and control interventions are detailed in Table 5. The 
investigators have safely and successfully implemented similar group intervention formats in previous 
studies. Engagement in sessions has been robust (83-92% across in-person and videoconference delivery 
formats) and no serious adverse events attributable to the interventions have been recorded (n=>500 
participants across studies, R33AT009110, NH170001). 
 
Table 5. TIDieR Intervention Elements Common to Both Groups 
Intervention Specific 
Participant Resources 
Materials and resources that support specific intervention content (see 
descriptions for Partners4Pain and Keys to Wellbeing). Includes print and 
electronic workbooks; access to education and skill training videos via a 
website for viewing in multiple formats (e.g., cell phone, computer 
tablet, etc.) 
Facilitator Materials 
Print and electronic manual with session checklists and safety protocols; 
Google Slide session presentations with embedded expert-led 
educational and skill training videos; technology and related peripherals 
(e.g., headsets) as needed 
Facilitator Training 
Community Facilitators from our Community Partner Organizations with 
experience leading group programs; 30 hours of competency-based 
training by the study investigators and Community Facilitators from 
previous studies 
Procedures 
Facilitator-led group sessions; includes viewing of expert-narrated videos 
specific to each intervention’s content, workbook reflection activities, 
and facilitator-led group discussions 
 
Participants are encouraged to practice in between sessions using the 
provided intervention-specific resources (e.g., workbooks, videos, etc.).  
Delivery Format 
Sessions offered in-person, via videoconference, or hybrid depending on 
community partner organization and participant needs. Group sessions 
with 7-16 participants per group 
Location 
See participating locations listed in section 4.3 
Timing, Schedule 
One session per week for 9 weeks 
90 minutes per session 
Similar to other educational programs offered in community partner 
organizations. 
Tailoring 
Participants will be encouraged to practice at home, focusing on 
intervention specific content that meets their needs 
Fidelity 
10% of the interventions will be monitored by study investigators, either 
in-person or remotely using a fidelity checklist which will assess 
completion of required session activities; review of weekly session 
facilitator documentation in REDCap regarding ability to deliver session 
activities as planned, including rationale for activities not completed 
 
11.2 
EXPERIMENTAL INTERVENTION (PARTNERS4PAIN) 
 

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PRP Study Protocol V5 October 2023 
Partners4Pain is informed by the COM-B model for behavioral interventions; it postulates that to 
achieve desired behavioral outcomes (e.g., engagement in positive self-management behaviors such as 
increased activity, decreased medication use, etc.), interventions must address an individual’s capability, 
opportunity, and motivational related needs.72 Application of the COM-B model provides guidance for 
assessing and addressing needs more specifically (e.g., what knowledge, skills, and resources are 
needed?) and mapping these to evidence based intervention solutions and formats that are most likely 
to meet the desired outcomes. Importantly, the COM-B model considers affordability, practicality, 
effectiveness/cost-effectiveness, acceptability, safety, and equity - all critical considerations for 
implementation and translation of an intervention over the longer term, particularly for populations 
experiencing health disparities.99 
 
Partners4Pain aims to impact pain and behavioral outcomes by addressing BP-PEHD needs for effective 
pain self-management behaviors. Content unique to Partners4 Pain includes education, skills training, 
and support in evidence based CIH strategies, (e.g., pain education; BP specific mobility, strength, and 
stabilization exercises; mindful movement and meditation; progressive muscle relaxation, guided 
imagery, etc.) augmented by evidence and theory based behavior change techniques (e.g., action 
planning, problem solving, graded tasks, social support, etc.) which will be built into the program.72,100 
An important feature of the program will be to provide individuals with resources and support that will 
empower them to identify what they need (e.g., more information, specific exercises, more or less 
support from others, etc.) and how to choose which resources are appropriate for them. This approach 
to self-management is currently being used by the investigators in ongoing studies (R33AT009110, 
NH170001, UH3AT008769, R34AT011209).  
 
11.3 
CONTROL INTERVENTION (KEYS TO WELLBEING) 
 
Keys to Wellbeing is a credible, active comparison for the experimental intervention and will control for 
contextual factors between groups (See Table 5). It will do so by aiming to impact general health related 
outcomes by primarily addressing BP-PEHD related capability needs, specifically general knowledge and 
awareness of health and wellbeing. Topics will include information and tips including keeping socially 
connected, finding meaning and purpose, sorting health facts from fiction, addressing mental health, 
and keeping physically fit. This intervention was developed to serve as an active comparison for another 
CIH self-management study focused on mindfulness (R33AT009110). Adherence and satisfaction rates 
have been 89% and 79% respectively, indicating its robustness as a credible control. 
 
11.4 
INTERVENTION FIDELITY 
 
Intervention fidelity will be assessed by study investigators using fidelity instruments that address 
whether content elements of intervention sessions were delivered along with facilitator competencies 
for intervention delivery. At least 10% of the sessions will be assessed either in person or via 
videoconference. We will use adapted fidelity instruments used in previous studies. Fidelity of 
intervention delivery will also be assessed by review of session checklists completed by the facilitators.  
 
11.5 
INTERVENTION ADHERENCE 
 

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PRP Study Protocol V5 October 2023 
Adherence to the experimental and active control interventions is defined as attending six or more of 
the nine total sessions. During each session, the intervention facilitators will document participant 
attendance including a checklist of activities covered during the session. Participation in at least 70% of 
session activities is considered sufficient for attendance. Engagement and satisfaction with study 
interventions will be queried during the month two assessment.  
 
11.6 
CONCOMITANT THERAPY 
 
Participants may continue to use self-management strategies (e.g., over-the-counter medications,  
exercise) or provider-based interventions such as prescription medications or complementary and 
integrative therapies (e.g., acupuncture, manual therapy) for the duration of the study. Use of 
medications, self-management strategies, and provider-based therapies for pain will be assessed and 
documented in the baseline and follow up surveys.  
 
11.7 
RESCUE THERAPY 
 
This project is assessing community-based self-management programs for spinal pain in populations 
that experience health disparities. Medical providers are not routinely available within community-
based self-management programs, thus rescue medication therapy will not be provided by the study. 
Participants requiring evaluation and provider-based management for back pain will be referred to their 
health care provider. 
 
12 INTERVENTION DISCONTINUATION & PARTICIPANT WITHDRAWAL 
 
The following describes intervention discontinuation and study participant discontinuation/withdrawal 
for the R61 Randomized Pilot Study and the R33 Randomized Hybrid Effectiveness-Implementation Trial.  
 
12.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
A study participant may discontinue from the experimental or active control interventions, but not from 
the study overall. In such cases, remaining study procedures will be completed as indicated by the study 
protocol. If a significant finding (e.g., development of an exclusion criterion) is identified after 
enrollment, the investigator or qualified designee will determine if any change in participant 
management is needed. Any new significant findings will be reported as an adverse event (AE). 
 
All efforts will be taken to facilitate study participants’ completion of the study interventions. However, 
participants may be discontinued from their assigned intervention if, for example: 
• 
They develop an exclusion criterion (new or not previously recognized) that would make it 
unsafe for them to continue  
• 
They exhibit significant study intervention non-compliance (e.g., disruptive or unsafe behavior) 
• 
Any adverse event (AE), medical condition, or other situation occurs such that continued 
participation in the study would not be in the best interest of the participant  

39 
PRP Study Protocol V5 October 2023 
• 
New evidence emerges which suggests it is unsafe for the participant(s) to proceed with the 
study  
• 
Participant withdraws consent to continue 
 
The data to be collected at the time of study intervention discontinuation, and for the remainder of the 
study will include the following: 
• 
Reason for intervention discontinuation and methods for determining the need to discontinue 
• 
Number of completed intervention visits 
• 
AE/SAE information, if indicated 
• 
Self-report surveys will continue to be administered as scheduled, even though the participant 
has discontinued study interventions 
 
12.2 
PARTICIPANT WITHDRAWAL FROM STUDY 
 
A study participant is free to withdraw from participation in the study at any time upon request. An 
investigator may also discontinue a participant from the study for reasons including, but not limited to, 
the following: 
• 
Participant develops an exclusion criterion (new or not previously recognized) that would make 
it unsafe for them to continue  
• 
Participant exhibits significant study intervention non-compliance (e.g., disruptive or unsafe 
behavior) 
• 
Any adverse event (AE), medical condition, or other situation occurs such that continued 
participation in the study would not be in the best interest of the participant  
• 
New evidence emerges which suggests it is unsafe for the participant(s) to proceed with the 
study  
• 
A major change occurs in the participant's life (e.g., incarceration, death) 
• 
Study closure by institute or oversight body 
• 
Participant withdraws consent to continue 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the Study 
Completion Case Report Form (CRF) in REDCap and participants will be notified. Subjects who sign the 
informed consent form and are randomized but do not receive the study intervention will not be 
replaced. Subjects who sign the informed consent form, are randomized and receive the study 
intervention, and subsequently withdraw, or are discontinued from the study, will not be replaced. 
 
12.3 
LOST TO FOLLOW-UP 
 
The R61 pilot study has one follow-up data collection assessment, so criteria for considering a 
participant lost to follow up to inform further data collection is not required. 
 
For the R33 phase, a participant will be considered lost to follow-up if they fail to complete two 
consecutive follow up data collection assessments and study staff are unable to contact the participant 
after at least 3 phone calls (which will be documented in the study record). Further details on processes 
for enhancing study retention are provided in section 9.4. 

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PRP Study Protocol V5 October 2023 
13 STUDY ASSESSMENTS & PROCEDURES 
 
The following describes study assessments and procedures for the R61 Randomized Pilot Study and the 
R33 Randomized Hybrid Effectiveness-Implementation Trial.  
 
13.1 
SCHEDULE OF ASSESSMENTS 
 
Table 6 details the schedule of assessments for Study Participants in the R61 Randomized Pilot Study 
and the R33 Randomized Hybrid Effectiveness-Implementation Trial.  
 
Table 6. Schedule of Assessments for Study Participants** (R61 Randomized Pilot Study and R33 
Randomized Trial) 
 
Initial 
Screen 
BL1 
BL2 
Intervention 
Sessions 1-9 
Month 2 
(-21 to 
+28 days) 
R33 Only 
Month 4  
(-21 to +28 
days) 
Month 6 
(-21 to +28 
days) 
Flow Data for Feasibility Outcomes+ 
Feasibility of recruitment, enrollment, 
intervention, and data collection rates 
X 
X 
X 
X 
X 
 
 
Baseline Assessments  
PhenX toolkit: Demographics & Core 
SDH Measures 
X 
X 
X 
 
 
 
 
Informed Consent 
X 
X 
X 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
X 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
Intervention Assessments 
Intervention Attendance, Session 
Activities, Intervention Administration 
Form 
 
 
 
X 
 
 
 
Effectiveness Measures* 
Pain intensity 
 
X 
X 
 
X 
X 
X 
Pain interference 
 
X 
X 
 
X 
X 
X 
Pain impact and frequency 
 
X 
X 
 
X 
 
X 
Self-efficacy for managing chronic 
conditions 
 
 
X 
 
X 
X 
X 
Domain specific life satisfaction 
 
 
X 
 
X 
X 
X 
Physical functioning 
 
 
X 
 
X 
X 
X 
Pain catastrophizing 
 
 
X 
 
X 
 
X 
Interoceptive awareness 
 
 
X 
 
X 
X 
X 
Satisfaction/Improvement 
 
 
 
 
X 
X 
X 
Medication use (including opioids) 
 
 
X 
 
X 
X 
X 
Participation in social roles 
 
 
X 
 
X 
 
X 
CIH self-management use 
 
 
X 
 
X 
X 
X 
Healthcare use 
 
 
X 
 
X 
X 
X 
Sleep disturbance/duration 
 
 
X 
 
X 
 
X 
Depression 
 
 
X 
 
X 
 
X 
Anxiety 
 
 
X 
 
X 
 
X 
Substance use 
 
 
X 
 
X 
 
X 
Implementation and Disparity Mitigating Measures (guided by RE-AIM, COM, ConNECT) 
Views and opinions related to barriers, 
facilitators to interventions and study 
participation (see Table 9, Study 
Participants for details) 
X 
X 
X 
 
X 
 
 
Satisfaction with and use of specific 
program activities 
 
 
 
 
X 
X 
X 
COM Assessment Survey 
 
 
 
 
X 
 
 

41 
PRP Study Protocol V5 October 2023 
 
Initial 
Screen 
BL1 
BL2 
Intervention 
Sessions 1-9 
Month 2 
(-21 to 
+28 days) 
R33 Only 
Month 4  
(-21 to +28 
days) 
Month 6 
(-21 to +28 
days) 
Supportive Environmental and 
Relational Alliance Survey 
 
 
 
 
X 
 
 
Other Measures 
Adverse events/side effects 
 
 
 
X 
X 
X 
X 
Study Completion Form 
 
 
 
 
X (R61) 
 
X (R33) 
**Schedule of quality improvement data collection activities can be found in Table 9 
*Effectiveness measures collected in R61 for purpose of assessing data collection feasibility only 
+Flow data is collected for the purposes of assessing feasibility areas for refinement in the R61 pilot study (including assessing RE-AIM factors) 
 
 
13.2 
SCREENING ASSESSMENTS 
 
13.2.1 INITIAL SCREEN 
 
Potential participants will be initially screened for eligibility using direct electronic data entry in REDCap 
administered to the participant either through a web-based survey or a phone screen with trained study 
staff. Both processes will include an introduction to the study and participants will be required to 
provide verbal or electronic consent prior to providing information (See section 16.1). Participants will 
be asked a limited number of questions regarding basic eligibility criteria and demographics to ensure 
they qualify (e.g., age, race/ethnicity, history of chronic back or neck pain, pregnancy). Study staff will 
speak with eligible individuals to answer any questions they may have and schedule them for a first 
baseline screening visit.  
13.2.2 BASELINE ONE SCREEN 
 
The first baseline assessment will take place up to 90 days after the initial screen described above. This 
evaluation will be conducted face-to-face either in person or via videoconference and will included the 
following activities:   
● Trained study staff will perform informed consent (see Consent Procedures in Section 16.1) 
● The Folstein Mini-Mental Status Examination (MMSE) will be administered to participants if 
cognitive impairment is suspected (e.g., repeating questions, unable to respond to/follow basic 
instructions)  
● Participants will complete a self-report web-based survey of questions to assess eligibility and 
collect baseline assessments for the following: 
o Demographic, occupational, and pain and health-related characteristics, including 
recommended common data elements for the study of pain117,130  
o Self-reported effectiveness and implementation outcome measures detailed in Table 6 (see 
section 14.2 for detail on individual measures) 
● Staff will schedule Baseline Two screening visit 
13.2.3 BASELINE TWO SCREEN 
A second baseline assessment will take place up to 90 days after BL1. This evaluation may be conducted 
in-person, via videoconference, or by phone and will include the following activities:  
● Trained study staff will confirm consent for participation (See Section 16.1) 

42 
PRP Study Protocol V5 October 2023 
● Participants will complete a brief self-report web-based survey to confirm eligibility for exclusion 
criteria that may have developed after the BL1 evaluation (e.g., pregnancy, cancer treatment) 
● Participants will complete baseline assessment for self-reported outcome measures listed in 
Table 6 (see Section 14.2 for detail on individual measures) and the PhenX toolkit measure for 
discrimination in healthcare.101 
● Eligible participants will be enrolled in the study and randomized to either the Partners4Pain or 
Keys to Wellbeing intervention program.  
 
13.3 
INTERVENTION SESSIONS 
 
The group interventions will start within 28 days of randomization. Community Facilitators will 
document attendance and presence for activities covered during weekly intervention visits using an 
intervention administration form in REDCap. 
 
13.4 
FOLLOW-UP ASSESSMENTS 
 
Follow up assessments of Effectiveness and Implementation/Disparity Mitigating Measures (see Table 6 
Schedule of Assessments) will be completed 2 months after the group interventions begin for the R61 
Randomized Pilot Study and 2, 4 and 6 months after the group interventions begin for the R33 
Randomized Hybrid Effectiveness-Implementation Trial. Details on individual measures are provided in 
section 14.2. 
 
13.5 
ADVERSE EVENTS & SERIOUS ADVERSE EVENTS 
 
13.5.1 DEFINITION OF ADVERSE EVENTS 
 
An adverse event (AE) is any untoward medical occurrence in a subject during participation in the R61 
Randomized Pilot Study, the R33 Hybrid Effectiveness-Implementation Trial, or with use of the 
interventions being studied. An adverse finding can include a sign, symptom, abnormal assessment 
(laboratory test value, vital signs, etc.), or any combination of these regardless of relationship to 
participation in the study. If there is any doubt as to whether an observation is an AE, the event will be 
recorded.   
13.5.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• 
Results in death 
• 
Is life-threatening (places the subject at immediate risk of death from the event as it occurred) 
• 
Results in inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in a persistent or significant disability or incapacity 
• 
Results in a congenital anomaly or birth defect  
An important medical event that may not result in death, be life threatening, or require hospitalization 
may be considered an SAE when, based upon appropriate medical judgment, the event may jeopardize 

43 
PRP Study Protocol V5 October 2023 
the subject and may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition. 
13.5.3 CLASSIFICATION OF AN ADVERSE EVENT 
 
The following guidelines will be used to grade the severity of adverse events: 
• 
Mild: no intervention required; no impact on activities of daily living (ADL) 
• 
Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on ADL 
• 
Severe: significant symptoms requiring invasive intervention; subject seeks medical attention, 
needs major assistance with ADL 
• 
Serious: results in death; life threatening; requires inpatient hospitalization; results in persistent 
or significant disability; congenital anomaly or birth defect. 
13.5.4 RELATIONSHIP TO STUDY PROCEDURES  
 
All adverse events (AEs) will have their relationship to study procedures, including the intervention, 
assessed by a PI, or designee, on temporal relationship. The degree of certainty about causality will be 
graded using the categories below (see Table 7). 
 
Table 7. Relationship of Adverse Events to Study Procedures 
Relatedness 
Definition 
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 related to another etiology. There must be an alternative, definitive etiology 
documented. 
 
13.5.5 EXPECTEDNESS 
 
The PIs are responsible for determining whether an AE or SAE is expected or unexpected. An adverse 
event will be considered unexpected if the nature, severity, or frequency of the event is not consistent 

44 
PRP Study Protocol V5 October 2023 
with the risk information previously described for the intervention and/or study (e.g., risk information in 
the consent form, natural history of the condition). 
 
13.5.6 TIME PERIOD & FREQUENCY FOR EVENT ASSESSMENT & FOLLOW-UP 
 
The PI, or designee, will record all reportable events with start dates occurring any time after 
randomization until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. 
Study related AE/SAEs will be followed to stabilization/resolution. 
 
13.5.7 ADVERSE EVENT & SERIOUS ADVERSE EVENT REPORTING  
 
Reporting for adverse events, serious adverse events, and other expedited events is summarized in 
Table 8. 
 
Table 8. Reporting for Adverse events, Serious adverse events, and Other events 
Event 
Report to…. 
 
Reporting Time 
Serious AE or AE – unexpected and at least 
probably related to the research procedures. 
UMN IRB 
The IRB defines prompt reporting to be within 5 
business days. If an RNI is not filed within 5 
business days, explain why the delay in reporting 
occurred and how prompt reporting will be 
ensured in the future. 
Serious AE – unexpected and related to the 
intervention 
NCCIH PO; IMC 
7 days 
Serious AE – anticipated or unrelated  
 
NCCIH  
IMC 
IRB 
AE(s) will be summarized in IMC reports. IMC 
reports will be distributed to the IMC and NCCIH 
per the guidelines in the IMC Charter and DSMP. 
IMC reports will be submitted to the IRB as an RNI 
within 5 business days of the IMC meeting 
minutes being signed or sent to IMC in lieu of a 
meeting.  
Unexpected Death or life-threatening AE related 
to the intervention 
 
NCCIH Program 
Officer, IMC 
3 days of the investigator becoming aware of the 
event 
Unexpected Death: Unexpected death of a locally 
enrolled participant whether considered related 
to the research or not. Death is considered 
unexpected if the risk of death is not listed in the 
consent form 
UMN IRB 
The IRB defines prompt reporting to be within 5 
business days. If an RNI is not filed within 5 
business days, explain why the delay in reporting 
occurred, and how prompt reporting will be 
ensured in the future. 
Risk: Information that indicates a new or 
increased risk, or a safety issue. For example: 
 
New information (e.g., an interim analysis, safety 
monitoring report, publication in the literature, 
sponsor report, or investigator finding) indicates 
UMN IRB 
The IRB defines prompt reporting to be within 5 
business days. If an RNI is not filed within 5 
business days, explain why the delay in reporting 
occurred, and how prompt reporting will be 
ensured in the future. 

45 
PRP Study Protocol V5 October 2023 
an increase in the frequency or magnitude of a 
previously known risk, or uncovers a new risk 
 
An adverse event that indicates a potential 
increase in risk or reduction in benefit (such as 
those that may prompt a change to the protocol 
or consent form) 
 
Protocol violation that harmed participants or 
others or that indicates participants or others 
might be at increased risk of harm 
 
Complaint of a participant that indicates 
participants or others might be at increased risk of 
harm or at risk of a new harm 
 
Confidentiality – unauthorized disclosure of 
confidential information  
UMN IRB 
The IRB defines prompt reporting to be within 5 
business days. If an RNI is not filed within 5 
business days, explain why the delay in reporting 
occurred, and how prompt reporting will be 
ensured in the future. 
PO: program officer; AE: adverse event; IRB: Institutional Review Board; UMN: University of Minnesota; RNI: Report of New 
Information; IMC: independent monitoring committee; NCCIH: National Center for Complementary and Integrative Health 
 
13.5.8 EVENTS OF SPECIAL INTEREST 
 
Reporting of certain events is required by law (e.g., suspected child abuse, vulnerable adult abuse or 
neglect, excessive use of alcohol or use of controlled substances for non-medical reasons during 
pregnancy) and may be discovered during the study. If information becomes available that may require 
mandated reporting, study staff will contact the PIs or Project Coordinators (also see 
https://mn.gov/dhs/general-public/licensing/maltreatment-investigations/mandated-reporter-
resources) 
 
13.5.9 REPORTING OF PREGNANCY 
 
Pregnancy, current or planned, at the point of enrollment is an exclusion criterion for the trial. Enrolled 
subjects who become pregnant may receive study interventions if there are no increased risks to the 
pregnant person or fetus. Approval will be sought from the IRB prior to intervention continuation. Such 
participants will be followed for the remainder of the study for outcome ascertainment. If treatment 
discontinuation is necessary, the reason for discontinuation will be reported in semi-annual reports to 
the Independent Monitoring Committee. 
 
13.6 
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 the following criteria: 

46 
PRP Study Protocol V5 October 2023 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the subject 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 subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
 
13.6.1 UNANTICIPATED PROBLEMS REPORTING 
 
The PI, or designee, will report Unanticipated Problems (UP) Involving Risks to Subjects or Others 
(UPIRTSOs) to the IRB within 5 business days of learning of the event. The UP report will include the 
following information. 
• 
Protocol identifying information: protocol title and number, PI names, and the IRB project 
number 
• 
A detailed description of the nature and severity of the event and the likely impact of the event 
on risk to study participants or others 
• 
Date the event occurred; date the study team became aware of the information 
• 
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 
• 
A description of whether the information indicates a new or increased risk, or a safety issue 
• 
A description of any changes to the informed consent documents and plans for notifying 
participants, if necessary 
 
14 OUTCOMES 
 
The choice of outcomes has been guided by: 
• 
The RE-AIM Framework, to ensure future success of the trial and future long-term translation of 
the interventions 
• 
The ConNECT Framework, to ensure Community Stakeholders are engaged earlier and more 
frequently in the research process 
• 
The hybrid effectiveness-implementation trial design, to ensure simultaneous measures of 
effectiveness and implementation are captured 
• 
The biopsychosocial model, to ensure biophysical, psychological, and social measures relevant 
to back pain in populations who experience health disparities are addressed 
• 
Alignment with HEAL core and supplementary outcome measures 
 
14.1 
R61 OUTCOMES 
 
The purpose of the R61 is to assess needs, optimize study intervention and approaches, and evaluate 
feasibility of the interventions and study approaches in preparation for the R33 Randomized Hybrid 

47 
PRP Study Protocol V5 October 2023 
Effectiveness Trial. This will be accomplished by gathering views and opinions, as well as flow data (see 
below).  
14.1.1 VIEWS AND OPINIONS 
 
Community Stakeholder and Study Participant views and opinions will be gathered and used to 
incorporate non-researcher views into the research process, and contribute to co-learning and co-
development, which are important features of community engaged research. Data collection methods 
will include survey questions (closed- and open-ended), interviews, focus groups, field notes; secondary 
analyses of previous IRB approved qualitative data will also be used. 
 
The schedule of data collection of Community Stakeholder and Study Participant views and opinions can 
be found in Table 9. This information will augment the investigators previous and ongoing research and 
the scientific literature.10,82,89,90,102   
Table 9.  Schedule of Quality Improvement Data Collection 
 
R61 Phase 
R33 Phase 
Entire Project 
Project Population Level 
Assess Needs; 
Optimize 
Interventions, 
Approaches 
(Pre-Pilot Study, 
Mixed Methods 
Quality Improve-
ment Activities) 
Evaluate Feasibility, 
Areas for Refinement 
(Randomized Pilot 
Study) 
 
Evaluate Effectiveness and 
Impact of Health Disparities; 
Assess and Describe 
Implementation, Disparity 
Mitigating Factors 
(Randomized Hybrid 
Effectiveness-Implementation 
Trial) 
Throughout 
Project, Time 
Independent (As 
they arise) 
Community Stakeholders  
Views, opinions re: barriers and facilitators 
to pain management, self-management 
identification of capability, opportunity 
and motivational (COM, BPS), 
implementation (RE-AIM), and disparity 
mitigating needs (RE-AIM, ConNECT, COM-
APEASE) 
X 
 
 
 
X 
Views, opinions re: solutions to address 
needs identified above 
X 
 
 
 
X 
Reactions, opinions re: resources and 
approaches for R61 Pilot Study (e.g., 
recruitment materials, workbooks, videos, 
etc.) 
X 
 
 
X 
Views and opinions of R61 Pilot Study 
Results; ideas for optimizing interventions 
and study approaches for R33 Randomized 
Trial 
 
X 
 
X 
Views and opinions of R33 Randomized 
Trial Results; ideas for addressing 
implementation and disparity mitigating 
needs to prepare for translation to 
community settings 
 
 
X 
X 
Views/opinions re: intervention 
affordability, practicality, effectiveness, 
acceptability, safety, and equity; factors 
that will facilitate adoption, 
implementation, maintenance (RE-AIM, 
ConNECT) at community and 
organizational level 
 
 
X 
X 
Study Participants 
Views/opinions re: barriers/facilitators to 
recruitment, enrollment; reach (RE-AIM) 
 
X 
X 
 

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PRP Study Protocol V5 October 2023 
 
R61 Phase 
R33 Phase 
Entire Project 
Project Population Level 
Assess Needs; 
Optimize 
Interventions, 
Approaches 
(Pre-Pilot Study, 
Mixed Methods 
Quality Improve-
ment Activities) 
Evaluate Feasibility, 
Areas for Refinement 
(Randomized Pilot 
Study) 
 
Evaluate Effectiveness and 
Impact of Health Disparities; 
Assess and Describe 
Implementation, Disparity 
Mitigating Factors 
(Randomized Hybrid 
Effectiveness-Implementation 
Trial) 
Throughout 
Project, Time 
Independent (As 
they arise) 
Views/opinions re: extent to which 
program met capability, opportunity, 
motivational (COM) needs; facilitates 
implementation (RE-AIM) 
 
X 
X 
 
Views/opinions re: intervention 
affordability, practicality, effectiveness, 
acceptability, safety, and equity; factors 
that will facilitate adoption, 
implementation, maintenance (RE-AIM, 
ConNECT) at individual level 
 
X 
X 
 
Views/opinions re: ability of the study 
team to create supportive environment, 
develop relational alliances that motivate 
engagement (COM), are inclusive and 
culturally sensitive (ConNECT); factors that 
will facilitate adoption, implementation, 
maintenance at individual level  
 
X 
X 
 
COM=Capability, opportunity, motivation from the COM-B model; RE-AIM=Reach, Effectiveness, Adoption, Implementation, Maintenance as 
defined by the RE-AIM Framework 
 
14.1.2 FEASIBILITY OUTCOMES 
 
We will evaluate feasibility outcomes as part of the R61 Randomized Pilot Study by measuring Study 
Participant flow data, including rates of recruitment, enrollment, intervention acceptability/credibility, 
intervention fidelity. In addition, as part of determining feasibility, the funder (NCCIH) has approved 
specific transition milestones that must be met prior to moving forward with the R33 Randomized Trial 
(see Section 6.1).  
Feasibility measures include performance indicators for key study domains that will provide insight into 
the feasibility of conducting the future R33 Randomized Trial. They will also help us identify areas for 
refinement.  
● Recruitment feasibility is an important measure of our ability to reach individuals with BP-
PEHD. Feasibility and areas for refinement will be measured using flow data including the 
number of participants screened per month; percentage of screened participants from 
racial/ethnic minority groups; and percentage of screened participants who are 
socioeconomically disadvantaged. We will also measure the percentage of participants screened 
per month by recruitment method; percentage of screened participants from racial/ethnic 
minority groups by recruitment method; and percentage of screened participants who are 
socioeconomically disadvantaged by recruitment method.  
 
● Enrollment feasibility is another important measure of our ability to reach individuals with BP-
PEHD and ensure our study enrollment processes are not providing obstructions to 
participation. Enrollment feasibility will be measured using flow data including the number of 
participants enrolled per month; percentage of enrolled participants from racial/ethnic minority 
groups; percentage of enrolled participants who are socioeconomically disadvantaged. We will 
also measure the percentage of participants excluded by eligibility criterion; percentage of 

49 
PRP Study Protocol V5 October 2023 
participants declining participation; main reasons for declined participation; average time to 
enrollment from screening visits (e.g., initial screen, baseline 1).  
 
● Intervention acceptability and credibility feasibility is an important measure of the potential 
for the interventions’ (experimental and control) adoption and implementation; this will be 
measured using flow data including the percentage of enrolled participants not attending any 
sessions; percentage of enrollees attending less than 6 of 9 sessions; percentage satisfied with 
interventions; and percentage reporting participation in home practice. We will also measure 
the percentage of enrolled participants withdrawing from interventions and reasons for 
withdrawal from interventions.  
 
● Intervention fidelity feasibility is an important measure of the ability of Community Partner 
Organizations and Community Facilitators to be able to deliver the interventions as planned and 
adopt them over the long term. This will be measured by the percentage of required session 
activities delivered per session; percentage of intervention activities across intervention 
programs not performed by facilitator; and frequency of intervention activities not performed 
by facilitator. 
● Data collection feasibility as well as the usability and functionality of our data collection systems 
are critical measures of our ability to assess the effectiveness and potential implementation of 
the interventions in the future R33 Randomized Trial. Data collection feasibility will be assessed 
by the percentage of enrollees completing the month 2 assessment; the percentage of missing 
variables by data collection instrument; reasons for missed assessments; and average duration 
of assessments (see also Table 6, Schedule of Assessments).  
 
 
14.2 
R33 RANDOMIZED HYBRID EFFECTIVENESS-IMPLEMENTATION TRIAL 
 
The purpose of the R61 is to evaluate the effectiveness of the interventions and the impact of health 
disparities. Community Stakeholder and Study Participant views and opinions will also be gathered to 
facilitate translation of the interventions to community settings.  
Data collection methods will include surveys, interviews, focus groups, field notes, and flow data (e.g., 
screening and enrollment rates, etc.). The assessment schedule is summarized in Table 6 and Table 9.  
14.2.1 PRIMARY EFFECTIVENESS OUTCOME  
 
For R33 Aim 1, we will evaluate the effectiveness the Partners4Pain and Keys to Wellbeing interventions 
using self-report surveys at 2, 4 and 6 months, measuring the primary outcome.  
The primary outcome is pain intensity and interference with life enjoyment and general activity as 
measured by the Pain, Enjoyment of Life and General Activity (PEG) scale. The PEG is a brief three item 
scale derived from the Brief Pain Inventory that measures average pain intensity, interference with 
enjoyment of life, and interference with general activity in the past week. Each item is measured on a 0 
(no pain/does not interfere) to 10 numeric rating scale (pain as bad as you can imagine/completely 
interferes). The overall PEG score provides a single measure of pain intensity and interference and is the 
average of the individual item scores with a potential range of 0-10. The PEG has been shown to be a 

50 
PRP Study Protocol V5 October 2023 
reliable and valid measure in chronic pain populations with responsiveness that is similar to or better 
than other commonly used pain measures.103-105 
14.2.2 SECONDARY EFFECTIVENESS OUTCOMES 
For R33 Aim 1, we will evaluate the effectiveness the Partners4Pain and Keys to Wellbeing interventions 
using self-report surveys at 2, 4 and 6 months, measuring secondary outcomes. 
Secondary outcome measures include a range of measures consistent with the Biopsychosocial Model of 
Pain and are recommended common data elements from the HEAL initiatives core pain domains; in 
addition, we have included important PROMIS based measures with demonstrated reliability and 
validity in chronic pain populations.106 
• 
Pain impact and frequency over the past 3 months measured using the Graded Chronic Pain 
Scale-Revised (GCPS-R).107 
• 
Physical function using the PROMIS 6-item short form v2.0 which measures difficulty doing 
household activities and agreement with statements on health limitations in physical activities 
on a 1 to 5 scale.108,109  
• 
Sleep disturbance and duration using the PROMIS 6-item short form v1.0 which measures sleep 
quality on a 1 to 5 scale from very poor to very good in addition to agreement with statements 
on sleep quality on a 1 to 5 scale.108,109 The average amount of sleep per night in the past month 
will also be obtained. 
• 
Participation in social roles and activities using the PROMIS 4-item short form v2.0 which 
measures frequency of trouble doing activities for leisure, work, or with family or friends on a 1 
to 5 scale.108,109 
• 
Anxiety will be measured using the Generalized Anxiety Disorder-2 survey (GAD-2) which 
includes 2 questions that are summed for a total score that can range from 0 to 6.110 
• 
Depression will be measured using the Patient Health Questionnaire-2 (PHQ-2) which includes 2 
questions that are summed for a total score that can range from 0 to 6.110  
• 
Substance use will be assessed using the Tobacco, Alcohol, Prescription medications, and other 
Substance (TAPS) survey.111 The TAPS is comprised of an initial 4-item screen for substance use 
that may lead to further assessment with substance specific surveys when indicated based on 
the initial 4-item screen. 
• 
Pain catastrophizing will be assessed using the 6-item short form of the Pain Catastrophizing 
Scale.112  
• 
Self-efficacy for managing chronic conditions will be assessed using the PROMIS 4-item short 
forms for 1) managing daily activities; 2) managing symptoms; 3) managing emotions; and 4) 
managing social interactions.113 
• 
Interoceptive Awareness will be measured using the Multidimensional Assessment of 
Interoceptive Awareness survey instrument (V2) using the 1) noticing; 2) attention regulation; 3) 
emotional awareness; and 4) self-regulation subscales.114 
• 
Satisfaction with various domains of life (e.g., education, work, family life) will be assessed using 
the PROMIS 13-item domain specific life satisfaction measure.115 
• 
Self-reported use of CIH self-management strategies, medications (over-the-counter and 
prescription medications - including opioids), and health care (MRIs, injections, hospitalizations, 
surgeries, provider visits) for back or neck pain will be measured. 
• 
Participants will be asked to report potential side effects by choosing from a list generated from 
previous studies of pain self-management programs and known potential risks of exercise and 
mindfulness interventions (R33AT009110, NH170001, R34AT011209).  

51 
PRP Study Protocol V5 October 2023 
• 
Satisfaction with the interventions will be assessed using a question that has participants rate 
their overall satisfaction ranging from completely satisfied to completely dissatisfied.106  
• 
Overall improvement will be assessed with the Patient Global Impression of Change (PGIC) 
which has participants rate their overall change from very much worse to very much 
improved.106 
 
For R33 Aim 2, we will evaluate the impact of health disparity related factors on the effectiveness of 
Partners4Pain intervention for primary and secondary outcomes described above through subgroup 
analyses which account for the potential relationships and complexities between disparity factors. See 
Section 15.4.2.  
14.2.3 IMPLEMENTATION & DISPARITY MITIGATING OUTCOMES 
 
For R33 Aim 3, we will assess and describe views of factors that could facilitate implementation and 
mitigate disparities to prepare for the long-term translation of the intervention to community partner 
organizations within and beyond the trial. We will use mixed methods quality improvement data 
collection of Study Participant and Community Stakeholder views and relevant flow data.  
Study Participants will be asked to complete mixed methods surveys collected querying: 
• 
Views on barriers/facilitators to reach and participation 
• 
Perceived effectiveness of the interventions 
• 
Their satisfaction with and use of specific program activities 
• 
The extent to which they felt the program met their capability, opportunity, and motivational 
(COM) needs72  
• 
Their views of the intervention’s overall affordability, practicality, effectiveness, acceptability, 
safety, and equity (APEASE, which is part of the COM model) 
• 
The ability of the study team to create a supportive environment and develop relational 
alliances that fostered norms of inclusion and cultural sensitivity.80,93,116-120 This includes a 
measure detailing perceived discrimination in healthcare that will be adapted to assess 
perceived discrimination within the study.101  
 
Community Stakeholders will also participate in a mixed methods evaluation (e.g., via interviews, focus 
groups, field notes) of their views of the intervention’s APEASE features, the nature and quality of the 
researcher-community partnership, and other domains that emerge as important for sustainability and 
translation.121  
 
Flow data related to the implementation and disparity mitigating outcomes include: 
• 
Number, proportion, and representative characteristics of Study Participants; reasons for 
participation or not by social determinants of health factors 
• 
Number, proportion, and representative characteristics of Community Partner Organizations; 
reasons for participation 
• 
Number, proportion, and representative characteristics of Community Facilitators; reasons for 
participation  
 
15 STATISTICAL CONSIDERATIONS 
 

52 
PRP Study Protocol V5 October 2023 
15.1 
HYPOTHESES 
 
Phase I (R61): No hypotheses have been formulated for the R61 phase of the project given the focus on 
quality improvement and feasibility.  
 
Phase II (R33):  
Aim 1 Hypothesis: The Partners4Pain program will be more effective in reducing the primary outcome of 
pain intensity and interference, in addition to secondary outcomes relative to the Keys to Wellbeing 
program (active control).  
 
Aim 2 Hypothesis:  Through sub-group analyses accounting for complex relationships between disparity 
factors and multi-level evaluation of community stakeholders, we will gain insights into the program’s 
ability to mitigate disparities (e.g., by overcoming capability, opportunity, and motivational (COM) 
barriers, as well as obstacles related to affordability, practicality, effectiveness, acceptability, safety, and 
equity (APEASE)). 
 
15.2 
SAMPLE SIZE 
 
15.2.1 R61 RANDOMIZED PILOT STUDY  
 
A total of 30 to 60 individuals will be enrolled in the R61 Randomized Pilot Study. The sample size has 
been informed by previous pilot studies by the investigators who have found approximately 15-20 
individuals per group sufficient for informing the feasibility of larger, randomized clinical trials.118,119 We 
anticipate needing to consent approximately 60 to 80 participants to enroll 30 to 60 individuals into the 
trial. 
15.2.2 R33 RANDOMIZED HYBRID EFFECTIVENESS-IMPLEMENTATION TRIAL 
 
Our sample size for the R33 Randomized Hybrid Effectiveness-Implementation Trial is based on findings 
from the literature on the PEG instrument (our primary outcome measure), including data on 
responsiveness and variability.122,123 We want at least 80% power to detect a group difference of 
approximately one unit or 10 percentage points on the PEG (0-10 scale) based on the mean of the 2, 4, 
and 6 month measures. We conducted simulation studies mimicking the structure of our planned study 
to assess the impact of sample size and group treatment factors (class size and number of classes) on 
power and detectable group difference. We used data on back pain intensity from the active control 
intervention (Keys to Wellbeing) in our team’s recent trial of physical activity in older adults 
(R33AT00911) to inform intra-class correlation. We generated normally distributed longitudinal 
measurements from the 0-10 PEG scale with a moderate intra-individual correlation of 0.25, an intra-
class correlation of 0.05, and a residual standard error of 2.5 units.122,123 The mean response was a 
function of normally distributed individual- and class-level random effects (with variances chosen to 
achieve the above correlations) as well as a constant fixed effect of treatment at the 2-, 4-, and 6-month 
time points. The mean PEG during follow-up was compared between treatment groups using a linear 
mixed model with fixed effects for treatment and baseline PEG and random effects for individual and 
class. We carried out simulations across a number of scenarios with class sizes ranging from 10 to 16 
participants and a total sample size of 300. In all scenarios, our planned sample size yielded greater than 

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80% power for a treatment effect of approximately 0.9 units (0-10 scale), corresponding to a 
standardized between group effect size (mean difference/SD) of 0.36, which we regard as a clinically 
meaningful difference for pain intensity and interference, and is consistent with recommendations in 
the literature.124,125 To account for up to 20% loss to follow up, we plan to enroll a total of 376 
participants. 
15.3 
POPULATIONS FOR ANALYSES & GENERAL APPROACH (R33) 
 
The primary analysis for the R33 Randomized Hybrid Effectiveness-Implementation Trial will use an 
intent-to-treat (ITT) approach126 with all enrolled subjects included in the analysis. Per-protocol analysis 
including only participants compliant with study protocols will be conducted as a secondary analysis. 
Secondary analyses are exploratory and will not be corrected for multiple comparisons. We will use 
hierarchical linear mixed model regression analyses to account for repeated measures within trial 
participants (the unit of randomization) in addition to the clustering of individuals within classes when 
receiving the experimental or control interventions.127 Missing data analyses will be informed by the 
pattern and reasons for missing data and will include multiple imputation (data missing at random) and 
sensitivity analyses using pattern mixture models (data not missing at random), if appropriate.128,129 This 
approach has been applied in previous trials by the investigators and highlighted as an exemplar in 
Annals of Internal Medicine.130 
 
15.4 
DATA ANALYSES 
 
15.4.1 R61 PHASE 
 
Aims 1 & 2: Mixed method assessment will be conducted. Quantitative data will be analyzed using 
descriptive statistics when appropriate. For the qualitative analysis, experienced members of the study 
team will apply rapid deductive, directed content analytic methods of individual and group interviews in 
real-time, audio-recordings of interviews, and text from open-ended surveys.  The coding structure and 
operational definitions will be guided by the study’s conceptual models131,132 to provide insights into 
barriers and facilitators to future implementation.72,96,133,134 Directed content analyses will also allow for 
inductive gathering of important themes that might fall outside of our chosen models and 
frameworks.132 Rapid approaches have been advocated for implementation research as they balance 
rigor with efficiency, yielding timely and meaningful evaluation of stakeholder needs and perspectives 
that can be more quickly matched to solutions.131,135 This is in contrast to traditional qualitative methods 
which rely on resource-heavy methods including transcribing interviews verbatim and in-depth coding of 
transcripts which take more time. Given the short time frame between the R61 and future R33 study, a 
rapid analytic approach is most appropriate.  
 
In addition to using rapid qualitative approaches,132 we may also apply traditional qualitative methods 
when more nuanced information would be helpful. In these instances, we will use semi-structured 
interview guides for individual stakeholder interviews and focus groups which will be recorded and 
transcribed verbatim. Teams of 2-3 will perform in-depth, directed content analyses of the transcripts 
applying a codebook in NVivo qualitative software.136,137  We will use deductive approaches aligned with 
the study’s models and frameworks, as well as inductive thematic coding to document other important 
information that falls outside the coding structure. Representative quotations will be identified; when 

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useful (e.g., to gain insight as to theme importance) we will also quantify themes by categorizing them 
as present or absent for each case, and presented descriptively as frequencies.136,137   
 
Aim 3: Mixed method analyses will be conducted.136  Quantitative data will be presented using 
descriptive statistics (e.g. means, percentages). No between group statistical comparisons are planned 
for the R61 Randomized Pilot Study due to the small sample size and focus on feasibility. Qualitative 
data will be analyzed using the methods described above for Aims 1 and 2.  
 
15.4.2 R33 RANDOMIZED HYBRID EFFECTIVENESS-IMPLEMENTATION TRIAL 
 
Primary Analysis  
For the primary analysis, we will use mean PEG during follow-up (at 2, 4, and 6 months) as the outcome. 
The effect of treatment will be assessed using a hierarchical linear mixed model with fixed effects for 
treatment and baseline PEG and random effects for individual and class. In addition, we will test for 
evidence of an interaction between time and treatment by fitting a mixed model with an interaction 
between the treatment group indicator and follow-up time (viewed as a categorical random variable) 
and using a likelihood ratio test to assess whether the interaction terms are jointly significant. The 
results of this analysis will inform the interpretation of the primary analysis and guide secondary 
analyses. Analyses will be carried out using the statistical software R. 
 
Secondary Analyses 
Responder Analyses: We will derive responder categories for our primary outcome of pain intensity and 
interference (PEG) at 2, 4, and 6 months corresponding to reductions from baseline of 30% (minimal 
improvement), 50% (moderate improvement), 75% and 100% (substantial improvement). Then, we will 
fit proportional odds models to assess the effect of treatment on the probability of falling into each of 
these categories. In addition, we will conduct cumulative responder analyses to assess the proportion of 
responders for all possible levels of pain intensity and interference reduction (0 to 100% reduction).138 
 
Secondary Outcomes: Secondary numerical outcome measures (e.g., self-efficacy, life satisfaction, 
physical functioning) will be analyzed similarly to the primary PEG outcome. Generalized linear mixed 
models will be used for binary and count outcomes. 
 
Longitudinal Analyses: Systematic reviews and meta-analyses of interventions for chronic pain and 
chronic back pain commonly use short-, medium-, and long-term treatment effects for analysis. 
Therefore, in addition to the analyses of primary and secondary outcomes which provide a measure of 
cumulative burden over the six-month study period, we will conduct longitudinal analyses with time 
coded as a categorical variable to quantify group differences in primary and secondary outcomes at 2, 4, 
and 6 months. Differences in numerical outcomes will be assessed using linear mixed models as 
described above. Differences in categorical outcomes (e.g., Graded Chronic Pain Scale, health care use) 
will be assessed using multi-level mixed effects generalized linear models. 
 
Effect Heterogeneity Analyses: While it remains important to estimate the overall (mean) effect of an 
intervention, analyses of intervention studies have increasingly focused on characterizing how 
population subgroups experience differential treatment effects.139-141 Here, we will employ modern 
statistical machine learning methods (including some co-developed by co-I Wolfson142) to describe how 
disparity factors (i.e. race, ethnicity, income, wealth, education, health care access) interact to influence 
how responsive individuals are to treatment. These flexible methods combining matching techniques 

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with decision trees will allow us to carry out a formal statistical test for effect heterogeneity, and (in the 
presence of heterogeneity) also yield simple classification rules that partition the population according 
to their expected treatment effect. In previous work, we have successfully applied these techniques to 
randomized trials with fewer participants (n=180) than we will have in this study (n=376) so we 
anticipate that we will have an adequate sample size to achieve meaningful results. For these analyses, 
we will use a limited set of outcomes (e.g., PEG, self-efficacy) at 2, 4, and 6 months to characterize the 
treatment effect. All analyses are exploratory and will not be corrected for multiple comparisons. 
 
Mediation Analyses: In addition to characterizing how treatment effects vary across individuals, we will 
also explore the potential mechanisms driving these treatment effects via mediation analysis. 
Specifically, we will apply established methods143 to characterize the proportion of treatment effect for 
changes in pain intensity and interference at months 4 and 6 that can be explained by changes in self-
efficacy, interoceptive awareness, and domain-specific life satisfaction measured in prior months. 
Mediation models will be estimated using the mediation package in R.144 Further, we will apply 
decomposition methods145 to understand whether the relationship between treatment effects and self-
efficacy/life satisfaction is driven by mediation, moderation, or moderated mediation. 
 
Comparisons to Back Pain Populations with Low Health Disparities: To assess the impact of 
Partners4Pain on mitigating disparities in pain self-management, we will compare findings to results 
from studies assessing self-management programs for chronic back pain with low PEHD representation, 
including studies from the HEAL initiative.67,71 This includes studies by our team assessing the impact of 
self-management for chronic neck and back pain.3,4,6,8 We will assess the similarity of mean outcome 
levels at baseline, treatment effects, drivers of effect heterogeneity, and mediating variables. Where 
possible, we will combine individual-level data (from previous studies conducted by our team) to 
formally test differences across studies. 
 
Implementation and Disparity Mitigating Outcome Analyses: Qualitative measures will be analyzed 
using methods described previously (see R61 Aims 1 & 2). Quantitative measures will be summarized 
and compared between treatment groups using two-sample t-tests (for continuous measures) and chi-
square tests (for categorical measures). Exploratory analyses will employ regression and decision tree 
models to investigate the impact of disparity factors (i.e., race, ethnicity, income, wealth, education, 
health care access) on measures of program implementation.   
 
16 REGULATORY, ETHICAL, & STUDY OVERSIGHT 
 
16.1 
INFORMED CONSENT 
 
16.1.1 CONSENT & OTHER INFORMATIONAL DOCUMENTS  
 
Community Stakeholder Information Sheet 
Community Stakeholders (see Table 4) will be provided with an informational sheet prior to sharing their 
views and opinions. The information sheet details the names of the researchers, an explanation of what 
the community stakeholders will be expected to do and any risks associated with their involvement, and 
contact information for the IRB office and University of Minnesota in case of questions or concerns. 
 

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Informed Consent Form (Study Participants) 
The consent form will include, but is not limited to, the following: information regarding the study 
purpose and research design, study procedures, potential risks and benefits, alternatives to 
participation, voluntary nature of participation, privacy and confidentiality, research-related injury, 
disclosure of new information regarding participation, and who to contact outside the study in case of 
issues. Contact information for the PIs and project coordinator(s) will also be provided. Participants, 
study staff, and an impartial witness, as needed, will sign and date the consent form.  
 
Changes to the Informed Consent Form 
In the event the informed consent form changes, following necessary IRB approvals, study staff will 
meet with the PI or designee and review changes to the form prior to conducting consent with new 
study participants. If existing study participants need to be informed of specific changes in the risks or 
benefits of study participation, an addendum consent will be used. This addendum will be used to, for 
example, inform enrolled participants about significant new findings that may have a bearing on their 
willingness to continue participation in the study. The addendum consent will be given to the participant 
at a study visit, emailed, or mailed to the participant's home. 
 
16.1.2 CONSENT PROCEDURES & DOCUMENTATION 
 
Consent & Human Subjects Training 
All research staff obtaining informed consent are required to undergo project specific human subjects 
training that addresses the essential components to the informed consent process. Staff responsible for 
consenting participants will be documented in the study’s Delegation of Authority Log and in Ethos. In 
addition, staff will complete human subjects training in accordance with the UMN’s human subjects and 
HIPAA training requirements.   
 
This procedure establishes the process to obtain informed consent from participants. The process begins 
when an individual identifies as a potential candidate for the study and will continue throughout the 
duration of the study. The process ends when a participant declines consent to participate (e.g., prior to 
signing the consent, withdrawing consent) or when study completion occurs. Participants must 
demonstrate the ability to autonomously provide written or electronic consent. A Legally Authorized 
Representative (LAR) will not be used. The Principal Investigators are responsible for ensuring these 
procedures are carried out. 
 
Potential participants will consent at 3 different time points: during a brief initial screening survey and at 
each of the two baseline screening appointments.  
 
Initial Screening Survey/Pre-Baseline Screening Visit 
Interested individuals are initially screened using a web-based screening survey that can be completed 
independently online or over the phone with study staff. An overview of the study will be provided 
during the web-screen, and electronic consent secured prior to collecting preliminary information on 
eligibility (e.g., age, presence of chronic back or neck pain). Following the web-based screening, 
potential participants will be sent an informational video describing the study in more detail and will be 
contacted by study staff to answer any preliminary questions they may have (e.g., purpose of the study, 
interventions, time commitment) and schedule the first baseline screening appointment.  
 

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Baseline 1 Screening Visit 
This appointment can take place virtually or in-person at a participating study location. Prior to this 
appointment, participants will be given a copy of the consent document to review on their own. Study 
staff will verify the most current IRB-approved version of the consent form is used. Easy to understand, 
IRB pre-approved, electronic and print informational materials, including visual media, will be used to 
facilitate understanding of study procedures. As part of the informed consent process, potential 
research participants will be made aware of financial or business interests that may affect their decision 
to participate. None are anticipated; see Conflict of Interest Policy if a change in circumstance occurs. 
Study staff will review the consent form with the participants, section by section. This may be done one-
on-one or in a group setting with other potential participants. Following review of the consent form, 
participants will be invited to ask questions one-on-one with study staff in a private and quiet space. 
Research staff will assess comprehension and understanding of information presented in the consent 
form using a series of open-ended questions (e.g., study purpose, interventions, risks). Participants will 
be encouraged to discuss taking part in the research study with family members, friends and/or 
healthcare providers, as appropriate. Participants are encouraged to think about study participation and 
will not be coerced or pressured into deciding to participate before they are ready. Written or electronic 
consent will be obtained from each study candidate. Only individuals who demonstrate comprehension 
will be considered eligible to participate. If the participant cannot read, an impartial witness can be 
used. The impartial witness must: 
• 
Be present during the entire consent discussion to attest to the adequacy of the consent process 
and to the participant's voluntary consent. The witness must be present during the entire 
consent conversation, not just for signing the document(s). 
• 
The witness may be a family member, friend, caregiver etc. The witness may not be a person 
involved in the design, conduct, or reporting of the research study. 
 
All participants will be given a copy of the signed consent form for their personal records. Original signed 
paper consent forms will be secured in the respective participant's research file. Signed e-consent forms 
will be maintained in REDCap.  
 
Baseline 2 Screening Visit 
At the second baseline screening visit, research staff will review the study purpose and procedures (e.g., 
study visits, data collection) and confirm continued consent to participate. 
 
To complete the informed consent process at the end of study participation, study staff will inform the 
subject when their participation has ended and will document the discussion in the study record. 
 
16.2 
STUDY DISCONTINUATION & CLOSURE 
 
The study may be temporarily suspended or prematurely closed if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be provided to 
study participants, investigators and study collaborators, funding agency, and regulatory authorities, 
including the UMN IRB, by the PIs or designee. In the event of any type of closure, the PIs, or designee, 
will promptly inform ongoing study participants, the IRB, and sponsor/funding agency and provide the 
reason(s) for the termination or temporary suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 

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• 
Insufficient compliance of study staff to the protocol (i.e., significant protocol violations) 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Major difficulties with study recruitment or retention 
• 
Natural disaster, public health crisis 
  
The study may resume once concerns about safety, protocol compliance, and data quality are addressed 
and satisfy regulatory bodies (e.g., funding agency, IRB, IMC).   
  
STUDY CLOSURE  
  
The Principal Investigators, or their designee, have the responsibility of informing the IRB, and other 
regulatory bodies, when a protocol has been completed. A protocol is considered to be open and active 
until the investigator has notified the IRB the study has been completed.  
 
Study Close Out Procedures are as follows: 
• 
Confirm a signed ICF is on file for each participant 
• 
All CRFs for each participant are complete or closed; all other data entry is complete 
• 
Status of all outstanding data edits, queries, or missing data is known and there is a timeline for 
their resolution 
• 
Procedures for locking the database are complete or in progress 
• 
All regulatory and other pertinent study documents for the protocol are current, complete, and 
on file (e.g., IRB approvals, consent documents, current CRFs) 
• 
Inform IRB of study closure status or identify plans to this, per IRB reporting requirements 
• 
Notify monitoring committee of study closure status 
• 
Update clinicaltrials.gov 
• 
Update Study Closure Status 
• 
Post the study Informed Consent Form to clinicaltrials.gov 
• 
Study results will be submitted to clinicaltrials.gov no later than 12 months after the primary 
completion date) 
• 
Following publication of study findings, de-identified and non-traceable data generated by the 
project will be submitted to study-appropriate repositories in consultation with the HEAL Data 
Stewardship Group to ensure the data is accessible via the HEAL Initiative Data Ecosystem.  
 
16.3 
CONFIDENTIALITY & PRIVACY 
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, the IMC, and the 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.  
 
Authorized representatives of the funding agency, representatives of the Institutional Review Board 
(IRB), and other regulatory agencies may inspect all documents and records required to be maintained 
by the investigator for the participants in this study.  
 
The study participant’s contact information will be securely stored 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 

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dictated by the reviewing IRB, Institutional policies, or funding agency requirements. We will permit 
access to such records. 
 
The study will primarily capture data electronically, back up paper files will only be used when electronic 
data systems are unavailable. Electronic data will be housed on password protected; HIPAA compliant 
databases stored on secure servers also operated by the UMN Health Sciences Technology (HST). The 
servers are in a physically secure location on campus and are backed up nightly, with the backups stored 
in accordance with the HST. Hard-copy participant research files, with identifiable information, will be 
secured in a locked file cabinet, in a locked office, with no public access at the University of Minnesota 
(UMN). Further, study participants will be assigned a unique ID number. This ID number will be used in 
lieu of using identifiable information whenever possible. Identifiable information will be accessible to 
study-related personnel who have met the UMN’s training requirements for the Responsible Conduct of 
Research, HIPAA, and data security. 
 
Routine communication with study participants regarding scheduling and reminders for study visits will 
occur by phone or email. Authorization for email communication regarding scheduling and reminders 
for study visits will be obtained from participants.  
 
All published reports will be of summary nature and no individual subjects will be identified beyond the 
investigative staff involved in the project. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 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.  
 
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 subjects research are required to protect identifiable research information 
from forced disclosure per the terms of the NIH Policy (see https://humansubjects.nih.gov/coc/index). 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. 
16.4 
KEY ROLES & STUDY GOVERNANCE 
 
The structure and organization of the study team is summarized in Table 10 and is based on the 
investigators’ previous work successfully conducting complex milestone driven projects. 
 
Members of the study team represent a professionally diverse group of individuals from scientific and 
community settings and are at various stages of their research and professional careers. They have been 
strategically brought together based on their skills and experience which will enhance the likelihood of 
the project’s success.  
 
Due to the project’s complexity, there are two Principal Investigators (PIs).  
 

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Table 10. Key Roles and Study Governance 
Study Committee/Team/Hub 
Roles & Responsibilities 
Steering Committee 
(Comprised of PIs and Co-Is, 
Community Partner 
Organization Leadership 
Members as Co-I Consultants) 
• Provide guidance to the PIs related to the overall scientific agenda, 
decision making, monitoring of study progress and the dissemination and 
implementation plan 
• Facilitates relationships between researchers and Community Partner 
Organizations 
Management Team  
(Comprised of Co-I Hub Leads, 
PIs, Project Coordinators) 
• Oversees study development and implementation 
• Supports and monitors Individual Team Hub Progress 
• Develops/maintains Overall Study Team Charter 
• Maintains regular communication with Community Partner Organizations 
regarding study status and collaboration 
• Develops and routinely reviews protocol 
• Conducts regular review of study progress, timelines, budget, payment of 
consultants, etc. 
Project Coordination Hub 
(Comprised of Project 
Coordinators, PIs) 
• Coordinates research activities across hubs 
• Standardizes processes for priorities work-flow management using project 
management tools (e.g., ClickUp) 
• Identifies and brings attention to barriers obstructing timeline completion 
of milestones, time sensitive issues 
• Assembles and maintains entire study MOP; initiates timely review of MOP 
sections  
• Maintains Project Coordination MOP Sections 
Regulatory Hub* 
 
• Coordinates, develops, maintains, ensures compliance regarding: 
• IRB submissions  
• Protocol  
• AE/UPIRTSO reporting  
• Regulatory Binder 
• Delegation of Authority Logs 
• Coordinates, trains staff and ensures compliance re: Informed Consent 
Activities 
• Coordinates, ensures documentation and compliance of Human Subjects 
Training of study staff 
• Coordinates meetings, preparation of reports and responses related to 
Independent Monitoring Committee 
• Maintains timely reporting on Clinicaltrials.gov  
• Maintains Regulatory MOP Sections 
Data Collection and 
Management Hub* 
 
• Coordinates development of study CRFs 
• Develops and maintains study databases/management systems (REDCap) 
• Coordinates randomization system 
• Trains staff in data collection/management activities 
• Stores and manages all study related data 
• Prepares data for data analysis 
• Oversees quality assurance and quality control of data collection and data 
management 
• Prepares monitoring reports for internal and external reporting purposes 
• Maintains Data Collection and Management MOP Sections 
Intervention Hub* 
• Develops the intervention curricula for experimental and control  

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• Designs, develops, and produces intervention assets; seeks input from 
Community Stakeholders with the assistance of the Data Management 
Hub 
• Works with the Delivery Platforms, Technology Hub to produce website 
related content 
• Hires, trains, and managements Community Facilitators 
• Designs, develops intervention training materials for Study Staff and 
Community Facilitators 
• Designs, develops, and implements intervention CRFs, fidelity assessments 
in coordination with the Data Management Hub 
• Maintains Intervention MOP Sections 
Delivery Platforms, Technology 
Hub* 
• Assesses and makes recommendations for delivery platforms and 
technology to support participant facing activities  
• Develops and trains staff in the use of associated delivery platforms and 
technology 
• Coordinates the design, development and maintenance of the study 
related website Partners4Pain.org 
• Maintains Delivery Platforms, Technology MOP Sections 
Community Engagement and 
Recruitment Hub* 
• Develops and implements the recruitment plan 
• Develops and implements the engagement plan  
• Coordinates convening of Community Advisory Team  
• Works with the Data Management Hub to coordinate Community 
Stakeholder Quality Improvement Data Collection 
• Maintains Community Engagement and Recruitment Hub MOP Sections 
Communications, Public 
Relations Hub* 
• Develops and implements communications and public relations plans 
• Designs, develops, and produces communication assets (e.g., brand kit, 
press releases, newsletters, etc.) 
• Works with the Delivery Platforms, Technology Hub to produce website 
related content 
• Maintains Communications, Public Relations Hub MOP Sections 
Participant Coordination Hub* 
• Coordinates activities with Data Collection/Management and Community 
Engagement Hubs  
• Responsible for overseeing the implementation of all activities at a 
participant level; includes:  
• Reminder emails (sessions, follow up)  
• Scheduling visits  
• Monitoring communication systems  
• Troubleshooting and assisting participants as needed 
• Maintains Participant Coordination Hub MOP Sections 

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Community Advisory Team 
(Comprised of Community 
Members and Leadership from 
Community Partner 
Organizations Serving in 
Consultant Roles) 
 
 
 
 
 
 
 
 
 
 
 
Works in partnership with researchers to 
• Advise researchers on how to overcome barriers to engaging diverse 
populations in research participation 
• Connect researchers to other community organizations and community 
leaders to encourage community member participation in a range of 
research-related activities 
• Co-facilitate community talks and other conversations 
• Contribute to study conceptualization, design, development, 
implementation, results interpretation, and dissemination 
• Co-create and co-develop culturally sensitive research processes and 
materials 
• Contribute to decisions regarding new and ongoing projects upon 
researcher request 
• Expand reach to involve more communities in the research process 
• Disseminate recruitment materials through routine communication 
channels 
Community Champions 
(Comprised of individuals from 
varied organizational domains 
including health care 
professionals, faith-based 
leaders, charitable 
organizations, neighborhood 
associations, senior 
communities, etc.)  
• Disseminate recruitment materials through routine communication 
channels 
*Hubs (with the exception of the Project Coordination Hub) are comprised of at least one PI, at least one Co-I 
with subject matter expertise, and at least one Project Coordinator 
MOP=Manual of Operations 
 
16.5 
SAFETY OVERSIGHT 
 
Safety oversight for the study will be under the direction of an Independent Monitoring Committee, 
composed of 4 individuals with the appropriate expertise and experience in clinical trial monitoring, 
including safety monitoring. The IMC was chosen by the study team and approved by NCCIH. 
 
The DSMP and IMC Charter provide specific details regarding IMC membership, responsibilities, meeting 
and report frequency, and more. This committee is independent from the study conduct and free of 
conflicts of interest. 
 
16.6 
CLINICAL MONITORING 
 
Study monitoring will be conducted internally by the study team to ensure that the rights and wellbeing 
of trial participants are protected; that the reported trial data are accurate, complete, and verifiable; 
and the conduct of the trial is in compliance with the currently approved protocol/amendment(s), with 
International Council on Harmonization Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s). Self-monitoring activities are described in Section 16.7, Quality Assurance and Quality 
Control. 

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16.7 
QUALITY ASSURANCE & QUALITY CONTROL 
 
We will perform internal quality management of study conduct, data collection, documentation, and 
completion.  
 
Quality assurance and control procedures will be implemented as follows: 
 
Research staff will undergo project-specific training in informed consent, screening and enrollment 
procedures, data collection, safety assessment, and adverse event protocols prior to study enrollment. 
Study intervention facilitators will undergo project-specific training in screening and enrollment 
procedures, their respective interventions, and safety assessment and adverse event protocols prior to 
study enrollment. Certification by a principal investigator (or designee) requires adherence to standard 
operating procedures outlined in the manual of operations. Training and certification will be logged. 
 
Informed consent — Study staff will review both the documentation of the consenting process as well 
as completed consent documents for enrolled participants.  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.  
 
Outcome data collection — The primary method of data collection for participant self-reported 
outcomes will be direct electronic entry through a survey interface with REDCap. Logic rules specifying 
the type and range of acceptable responses will be programmed into REDCap. Participants will receive 
an error message if they enter an invalid response. The PIs will review reports on data capture and 
quality on a monthly basis. Missing data reporting and other customized reports will be developed in 
order to facilitate efficient workflow and high-quality data capture. Data collection instrument specific 
follow-up rates will be tabulated and reviewed during meetings between the PIs and study staff. 
Additional training will be provided as needed based on the findings. 
 
Intervention Fidelity — Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described in 
Section 11.4.  
 
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. 
 
16.8 
DATA HANDLING & RECORD KEEPING 
 
16.8.1 DATA COLLECTION & MANAGEMENT RESPONSIBILITIES 
 
Data collection and accurate documentation are the responsibility of the study staff under the 
supervision of the investigators. All source documents will be reviewed by the study team and data 
entry staff, who will ensure that they are accurate and complete. Unanticipated problems and adverse 
events will be reviewed by the investigator or designee.   
 

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Data collection for the study will be primarily web-based. Initial screening is conducted via a web-based 
form completed either directly by the subject or by study staff conducting an interview over the phone. 
Baseline screening and intervention-related data acquisition will be primarily direct-electronic entry but 
may include a small number of handwritten forms that are later keyed by study staff if electronic data 
systems are unavailable. Outcomes will be obtained primarily through web-based forms completed 
directly by subjects. In some instances, responses may be obtained through phone interviews by study 
staff or paper surveys mailed to subjects. These responses are then data-entered study staff. 
 
All handwritten data forms for enrolled patients will be scanned and uploaded to the data management 
system for review. A history of CRFs and all fielded versions will be maintained. CRFs will be 
implemented as web-based eCRFs including checks for valid entry and incomplete responses. 
 
Database Protection  
Data for this study will be entered into a REDCap database, which uses a MySQL database via a secure 
web interface with data checks used during data entry to ensure data quality. REDCap includes a 
complete suite of features to support HIPAA compliance, including a full audit trail, user-based 
privileges, and integration with the institutional LDAP server. The MySQL database and the web server 
will both be housed on secure servers operated by the University of Minnesota HST. The servers are in a 
physically secure location on campus and are backed up nightly, with the backups stored in accordance 
with the HST retention schedule of daily, weekly, and monthly tapes retained for 1 month, 3 months, 
and 6 months, respectively. Weekly backup tapes are stored offsite. The HST servers provide a stable, 
secure, well-maintained, and high-capacity data storage environment, and both REDCap and MySQL are 
widely used, powerful, reliable, well-supported systems. Access to the study's data in REDCap will be 
restricted to the members of the study team by username and password. The database incorporates an 
electronic audit trail to show change(s) to data after original entry including the date/time and user 
making the change. Electronic communication with outside collaborators will involve only non-
identifiable information. 
 
Source Document Protection 
Electronic source documents will be stored on a password protected computers supported and 
maintained by the UMN HST. Participant ID numbers will be used to protect participants’ confidentiality. 
All paper source documents will be stored in a locked file cabinet, in a locked office at the University of 
Minnesota with no public access. 
16.8.2 STUDY RECORDS RETENTION 
 
Study documents will be retained for a minimum of 3 years from the date of Federal Financial Report (FFR) 
submission. Documents may be retained for a longer period, if required by local regulations.  
 
16.9 
PROTOCOL DEVIATIONS 
 
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol, 
International Council on Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures 
(MOP) requirements. The noncompliance may be either on the part of the participant, the investigator, 
or the study site staff. As a result of deviations, corrective actions will be developed by the study team 
and implemented promptly, as required. It is the responsibility of investigators and research staff to 
follow the written protocol approved by the IRB.  

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PRP Study Protocol V5 October 2023 
 
Protocol deviations include, but are not limited to the following: 
• 
Failure to keep IRB approval up to date 
• 
Implementing protocol modifications without obtaining prospective IRB approval 
• 
Conducting research during a lapse in IRB approval 
• 
Enrolling more subjects than what is approved in the protocol 
• 
Performing research procedures outside the protocol specified window 
• 
Failure on the part of any individual involved in research review or oversight to abide by 
applicable laws or regulations, or the University of Minnesota IRB policies 
• 
Randomization of an ineligible participant; not-adhering to inclusion/exclusion criteria 
• 
Failure to obtain Informed Consent or altering from the informed consent process as described 
in the IRB approved protocol, including obtaining consent using an outdated consent form 
• 
Failure to report an SAE, Breach of Confidentiality, Unanticipated Problem 
• 
Failure to report an event that requires expedited reporting to the IRB (e.g., unexpected death, 
participant becomes incarcerated) 
• 
Wrong intervention administered to a participant 
 
Documenting and Reporting Requirements  
All protocol deviations, violations and research failures will be documented in REDCap by study staff. 
Deviations, violations, and research failures that are also SAEs, UPIRTSOs, or result in harm to the 
participant may have different, or additional, reporting requirements. See Sections 13.5 to 13.6 of this 
study protocol for more information.  
 
Protocol deviations and violations will be reported to regulatory agencies as required (e.g., IMC reports 
per reporting requirements outlined in the DSMP and/or Charter; per the UMN IRB and funding agency 
requirements).  
16.10 PUBLICATION & 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. Electronic copies of publications will be deposited within four weeks of acceptance by a 
journal in PubMed Central with proper metadata to be made discoverable and accessible upon 
publication. Publications will be made publicly available immediately without any embargo period and 
will be published under the Creative Commons Attribution 4.0 Generic License (CC BY 4.0) or an 
equivalent license or otherwise dedicated to the public domain (e.g., Creative Commons public domain 
tool, CC0). 
 
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 generated by the project will be submitted to study-appropriate repositories in 

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PRP Study Protocol V5 October 2023 
consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL 
Initiative Data Ecosystem. To the extent feasible, underlying primary data will be shared simultaneously 
with publications and made immediately accessible through release under the CC BY 4.0 or an 
equivalent license or otherwise dedicated to the public domain (e.g., Creative Commons public domain 
tool, CC0). Considerations for ensuring confidentiality of these shared data are described in Section 
16.12. 
 
16.11 CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence is critical. Therefore, any 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 University of Minnesota has established policies and procedures for 
all study group members to disclose all potential conflicts of interest and will establish a mechanism for 
the management of all reported dualities of interest. 
 
UMN researchers must adhere to Board of Regents and Administrative conflict of interest policies that 
require the timely disclosure of financial and business interests relating to the researcher’s University 
responsibilities and expertise. Disclosure of these interests is required annually and within 30 days of a 
“change in circumstances” using the Report of External Professional Activities (REPA). Current REPA 
reports are maintained for study staff (paid faculty, P&A employees and other individuals designated by 
a senior UMN leader or designate) with study regulatory documents. Covered individuals must complete 
the University’s conflict of interest course when filing the REPA for the first time, and every four years 
thereafter. University investigators must disclose all reportable conflicts to the University’s Office of 
Institutional Compliance (OIC). 
 
The existence of financial and/or business interests related to the research study will be disclosed in the 
New Study and Continuing Review forms in ETHOS for all study personnel. Any conflict not previously 
disclosed to the IRB will be reported via the Reportable New Information SmartForm in ETHOS. The 
investigators will also submit a modification in ETHOS to address any revisions to the study if required. 
 
The following strategies may be employed when COIs or potential COIs are identified. The strategies 
below are organized from minimal to more restrictive management and are not an exhaustive list. 
Management plans will be submitted to the IRB for approval and other regulatory bodies will be notified 
per their respective policies (e.g., IMC, NIH). 
• 
Disclose (if legally permissible) the conflict in the informed consent form and in any publications 
or presentations related to the research 
• 
Restrict the conflicted person’s access to identifiable data 
• 
Restrict the conflicted person’s ability to determine eligibility status of prospective participants.  
• 
Restrict the conflicted person from obtaining informed consent 
• 
Restrict the conflicted person from adjudicating adverse events, serious adverse events and/or 
unanticipated problems 
• 
Restrict the conflicted person’s participation in data analysis and interpretation 

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PRP Study Protocol V5 October 2023 
• 
Remove conflicted person from involvement in the conduct of the study. This is a last resort 
consideration that may require regulatory approval (e.g, sponsor approval, steering committee 
approval). 
 
16.12 FUTURE USE OF DATA 
 
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 PIs 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). The study is funded by the NIH’s 
Helping End Addiction Long-term (HEAL) initiative and will comply with the HEAL Initiative’s Public 
Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data). This includes submitting 
de-identified and non-traceable data generated by the project to study-appropriate repositories in 
consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL 
Initiative Data Ecosystem. Plans for sharing data for future use will be disclosed to study participants 
during informed consent.   
 
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