Spinal Manipulation and Patient Self-Management for Preventing Acute to Chronic Back
Phase: PHASE3
Conditions: Acute Pain, Low Back Pain, Mechanical
Sponsor: University of Minnesota

 
 
 
 
PACBACK Clinical Study 
Protocol  
 
Spinal Manipulation and Patient Self-Management for  
Preventing Acute to Chronic Back Pain (PACBACK) 
 

 
 
PACBACK Protocol V8 page 2 
      
FULL PROTOCOL TITLE 
Spinal Manipulation and Patient Self-Management for 
Preventing Acute to Chronic Back Pain (PACBACK): 
A Randomized Clinical Trial 
 
Study Chairman or Principal Investigator:  
Gert Bronfort, PhD, DC 
Principal Investigator, Clinical Coordinating Center 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
 
Patrick Heagerty, PhD, MS 
Principal Investigator, Data Coordinating Center 
School of Public Health, Department of Biostatistics 
Box 357232, 1959 NE Pacific Street, Seattle, WA 98195 
 
Anthony Delitto PhD, PT, FAPTA 
Co-Principal Investigator, Clinical Coordinating Center 
School of Health and Rehabilitation Sciences 
University of Pittsburgh 
4029 Forbes Tower, Pittsburgh, PA 15260 
 
Mike Schneider, DC, PhD 
Co-Principal Investigator, Clinical Coordinating Center 
School of Health and Rehabilitation Sciences 
University of Pittsburgh Bridgeside Point 1 
100 Technology Drive, Suite 210, Pittsburgh, PA 15219 
 
Supported by:  
The National Center for Complementary and Integrative Health  
UG3AT008769 
UH3AT008769 
 
IRB Approval: June 28, 2023 
Clinicaltrials.gov #: NCT03581123 
 
Version 8 
 
 

 
 
PACBACK Protocol V8 page 3 
      
Tool Revision History 
Version Number: 3 
Version Date: January 2019 
Summary of Revisions Made:  
● Added Dr. Ryan Eskuri to study staff list 
●  Remove STarT Back screening tool from in-person screening visit. This is captured at the initial 
screening survey only. 
● Visit 2 for MC care can now occur (in-person or via phone) within 7 business days of visit 1 
(changed from 1-2 days by phone) 
● Changed eligibility criteria: 
“Acute or subacute LBP: At the time of randomization, the participant’s current episode of LBP 
(period of LBP preceded by at least 1 month without bothersome LBP) must be between 2 and 12 
weeks duration and the participant must report experiencing LBP that interferes with regular daily 
activities on less than half of the days over the past 6 months.”  was changed to  
 
“At the time of randomization, the participant’s current episode/aggravation of LBP must be 
between 2 and 12 weeks duration.  
 
Participants with no LBP, mild LBP, or moderate LBP on average in the month preceding their 
current episode are eligible.  
o The current episode/aggravation has to be a new episode or a worsening of the existing 
LBP.” 
● Added “Average LBP characterized as severe in the month preceding the current 
episode/aggravation” to the exclusion criteria 
● Chronic interference with daily activities added as a secondary outcome at months 6 & 12.  
 
Version Number: 4 
Version Date: March 2019 
Summary of Revisions Made: 
● Updated interventions to reflect DCs and PTs offering SMT and SSM at both CCCs 
● Updated Milestone dates (i.e., date of transition and end of UG3 phase) 
 
Version Number: 5 
Version Date: October 2019 
● Modifications to personnel  
● Visual trajectory questionnaire for pain collected at baseline and M12  
● Heal measure-Month 2: Remove PPC, HCE, TEX; Month 12: add POS  
● Intervention uptake (SSM, SSM+SMT participants only) will be collected at M6 & M12  
● Exacerbation of low back pain added as an expected AE to all treatment groups (natural history of 
the condition); further defined ‘awareness’ in the “PACBACK: Report AEs, Unanticipated 
Problems, and Protocol Noncompliance” to include ‘awareness after talking with the participant 
to gather more information.’  
● Frequency of intervention fidelity assessment updated to monthly for all treating clinicians for six 
months, quarterly thereafter.  

 
 
PACBACK Protocol V8 page 4 
      
● 5x sit to stand test added to baseline and W9 assessment  
● Implementation measures:  participating clinicians will complete surveys prior to intervention 
training, at the end of intervention training, annually and at the end of the UH3 trial. 
Added definition of loss to follow-up 
Version Number: 6 
Version Date: August 2020 
Summary of Revisions Made:  
● Updated non-key University of Pittsburgh personnel 
● Added Phase 3 disruption due to Covid-19 
● Added Partial Randomization Period(s) & Full Randomization Period(s) 
● Added Plans for Covid-19 monitoring 
● Added remote baseline screening procedures 
● Updated delivery of SSM and MC interventions  
● Added option to conduct informed consent via videoconference & document participant consent 
electronically in REDCap 
● Participants at all sites will be given information related to Covid-19 
● Added Covid-19 impact questionnaire & Telehealth Usability Questionnaire (TUQ) 
● Hypertension screening procedures updated 
● Analysis section updated to reflect partial randomization period 
● Virtual fidelity assessments can be recorded on Zoom 
 
 
Version Number: 7 
Version Date: August 2021 
Summary of Revisions Made: 
● Aim #1 was updated to “Prevention of cLBP at 12 months as measured by LBP Impact (from 
Promis-29) scale: 8-50 (Analysis of AUC for months 10-12).”Analysis section updated to reflect 
this modification. A rationale for this change is included.  
● Secondary Outcomes updated to include Prevention of cLBP at 12 months, as measured by the 
proportion of patients in each group meeting the definition by the NIH Task Force on Research 
Standards for Chronic LBP (i.e., ongoing LBP on ≥50% of days over past 6 months). Analysis 
section updated to reflect this modification. 
● Update Linda Hanson’s role and remove Co-Investigator Joel Stevens.  
● Update non-key personnel 
● Update Steering Committee members to include Drs. Roni Evans and Carol Greco 
● TUQ: all participants enrolled in the 2-arm phase will complete the TUQ at predefined time 
points. Participants who engage in virtual study visits will complete the TUQ. 
● Update UMN Research Clinic location 
● Updated UPITT research team Suite # 
● NSAID creams added as an allowed MC intervention 
 
 
 
 
 
 

 
 
PACBACK Protocol V8 page 5 
      
Version Number: 8 
Version Date: June 2023 
Summary of Revisions Made: 
● Added Amy Perkins, Carly Thiner, Lynn Winkel, Aditi Das, Tracey Murray, Erin Rozwat, Leslie 
Lesoon (non-key personnel) 
● Removed Mary Greer, Shane Conley, Donna Schneider, Heidi Mendenhall and Ryan Eskuri 
(non-key personnel) 
● Removed UPMC Centers for Rehab Services 
● Added Pete Murray, NCCIH Program Officer 
● Updated Wendy Weber, NCCIH study role 
● Robin Boineau’s role as NCCIH project scientist was taken over by Wendy Weber 
● Change in sample size from n=1180 to n=1000 
● Update study location to include Homewood Community Engagement Center Wellness Pavilion 
● Update pregnancy test requirements 
● Statistical analysis plan updated 
 
 
 
 

 
 
PACBACK Protocol V8 page 6 
      
 
TABLE OF CONTENTS 
Page 
 
PACBACK Clinical Study Protocol 
1 
Tool Revision History 
3 
TABLE OF CONTENTS 
6 
STUDY TEAM ROSTER 
8 
PARTICIPATING STUDY SITES 
12 
PRÉCIS 
16 
1. STUDY OBJECTIVES 
17 
2. BACKGROUND AND RATIONALE 
18 
3. STUDY DESIGN 
22 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS 
32 
5. STUDY INTERVENTIONS 
34 
6. STUDY PROCEDURES 
41 
7. SAFETY ASSESSMENTS 
53 
8. INTERVENTION DISCONTINUATION 
57 
9. STATISTICAL CONSIDERATIONS 
58 
10. DATA COLLECTION AND QUALITY ASSURANCE 
71 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY 
75 
12. COMMITTEES 
76 
13. PUBLICATION OF RESEARCH FINDINGS 
77 
14. REFERENCES 
78 
15. SUPPLEMENTS/APPENDICES 
89 
 
 
 
 
 

 
 
PACBACK Protocol V8 page 7 
      
STUDY TEAM ROSTER  
See “Participating Sites” for a complete list of site investigators.  
 
University of Minnesota-Clinical Coordinating Center 
Oliver Ang PT, MSLSC 
Physical Therapist 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Email: ang00005@umn.edu 
 
Robin Austin PhD, DNP, DC, RN-BC 
Research Staff 
School of Nursing 
University of Minnesota, 5-140 Weaver-Densford Hall 
308 Harvard Street SE, Minneapolis, MN 55455 
Phone: 612-624-1115 
Email: quis0026@umn.edu 
 
Aditi Das, MPH 
Research Coordinator 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (612) 626-6477 
Email: dasxx125@umn.edu 
 
Alex Haley JD, MBA 
Research Staff 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (612) 624-9459 
Email: haley045@umn.edu 
 
John Jodzio, BA 
Research Administrator 
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 
 
Doug Kennedy PhD 
Research Staff 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone (612) 625-6946 
Email: kenne829@umn.edu 

 
 
PACBACK Protocol V8 page 8 
      
Amy Perkins NP-F 
Nurse Practitioner 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: 952-288-3031 
Email: perkinsa@umn.edu 
  
Carly Thiner NP-F 
Nurse Practitioner 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: 952-836-5559 
Email: deboe086@umn.edu 
 
Don Thorpe III DC 
Chiropractor 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (903) 821-6893 
Email: thorp167@umn.edu 
 
Blong Vang, DC 
Chiropractor 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (651) 210-9657 
Email: doctorblong@yahoo.com 
 
Jennifer “Jenny” Walter, MScN, APRN, CNP 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: 612-672-1200 
Email: jenny.e.hague@gmail.com 
                                    
Hennepin Healthcare Integrative Health & The Berman Center for Outcomes and Clinical 
Research 
Ben Backus, DC 
Chiropractor 
Hennepin Healthcare Integrative Health Clinic & Specialty Center 
715 South 8th Street, Minneapolis, MN 55404 
Phone: 612-298-8563 
Email:  benjamin.backus@hcmed.org 
 
Richard Printon, DC 
Chiropractor 

 
 
PACBACK Protocol V8 page 9 
      
Hennepin Healthcare Integrative Health Clinic & Specialty Center 
715 South 8th Street, Minneapolis, MN 55404 
Phone: (612) 873-6302 
Email: richard.printon@hcmed.org 
 
The Berman Center for Outcomes and Clinical Research 
825 South 8th Street, Suite #440, Minneapolis, MN 55404 
 
University of Pittsburgh-Clinical Coordinating Center 
Christine (Chris) McFarland, BS, BA 
Senior Clinical Research Coordinator 
Department of Physical Therapy 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 500 
Pittsburgh, PA 15219 
Phone: (412) 383-4323 
Email: chrismcfarland@pitt.edu      
 
Kathryn E. Brown, PT, MS 
Clinical Research Physical Therapist 
PT-CTRC 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 470, Pittsburgh, PA 15219 
Phone: (412) 383-6735 
Email: keb166@pitt.edu 
 
Frank Imbarlina, DC 
Department of Physical Therapy 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 500, Pittsburgh, PA 15219 
Phone: 412-418-6606 
Email: imbarlina@msn.com 
 
Leslie Lesoon, PA-C 
Department of Physical Therapy 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 500, Pittsburgh, PA 15219 
Email: Leslie.lesoon@pitt.edu 
 
Sean Mathers, DC 
Department of Physical Therapy 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 500, Pittsburgh, PA 15219 
Phone: TBD 
Email: ksm68@pitt.edu 
 
Tracey Murray, BS 
Research Coordinator 
Department of Physical Therapy 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 500, Pittsburgh, PA 15219 

 
 
PACBACK Protocol V8 page 10 
      
Phone: 412-383-0966 
Email: tym2@pitt.edu 
 
Meenakshi (Minnie) Sundaram BPT, MS 
Research Coordinator 
Department of Physical Therapy 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 500, Pittsburgh, PA 15219 
Phone: (412) 648-7026 
Email: mes395@pitt.edu 
 
William (Bill) Tellin, DC 
Department of Physical Therapy 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 500, Pittsburgh, PA 15219 
Phone: 412-992-6768 
Email: wit13@pitt.edu 
 
Erin Rozwat PT, DPT, NCS 
Clinical Research Physical Therapist 
PT-CTRC 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 470, Pittsburgh, PA 15219 
Email: eer48@pitt.edu 
 
Debra Voss, PT 
Clinical Research Physical Therapist 
PT-CTRC 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 470, Pittsburgh, PA 15219 
Phone: (412) 383-6735 
Email: debra.voss@pitt.edu 
 
David Wortman, MPT 
Clinical Research Physical Therapist 
PT-CTRC 
University of Pittsburgh, Bridgeside Point 1 
100 Technology Drive, Suite 470, Pittsburgh, PA 15219 
Phone: (412) 383-6735 
Email: d.wortman@pitt.edu 
 
 
 
University of Washington-Data Coordinating Center 
 
Eric Meier, MS 
Biostatistician 
Department of Biostatistics 
University of Washington 
4333 Brooklyn Avenue NE, Box 359461, Seattle, WA 98195 
Phone: 206-450-0020 

 
 
PACBACK Protocol V8 page 11 
      
Email: emeier11@uw.edu 
 
Bryan A Comstock, MS 
Senior Biostatistician 
Department of Biostatistics 
University of Washington 
4333 Brooklyn Avenue NE, Box 359461, Seattle, WA 98195 
Phone: 206-543-1882 
Email: bac4@uw.edu 
 
Heather Herren MPH, RN 
UW Clinical Trial Center 
University of Washington 
6200 NE 74th Street, Suite 250, Seattle, WA 98115 
Phone: (206) 616-0418 
Email: hherren@uw.edu 
 
Chris Nefcy, BS 
DCC Software Engineer 
Department of Biostatistics 
University of Washington 
4333 Brooklyn Avenue NE, Box 359461, Seattle, WA 98195 
Phone: 206-685-8828 
Email: cnefcy@uw.edu  
 
PARTICIPATING STUDY SITES 
 
University of Minnesota-Clinical Coordinating Center 
 
Gert Bronfort, PhD, DC 
Principal Investigator 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (612) 301-9005 
Email: bronf003@umn.edu 
 
John Connett, PhD 
Co-Investigator 
Biostatistics, Epidemiology and Research Design 
Clinical and Translational Science Institute 
University of Minnesota 
717 Delaware Street SE, 2nd Floor, Minneapolis, MN 5455 
Phone: (612) 626-9010  
Email: john-c@ccbr.umn.edu 
 
Roni Evans PhD, DC, MS 
Co-Investigator 
Earl E. Bakken Center for Spirituality & Healing 

 
 
PACBACK Protocol V8 page 12 
      
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (612) 301-9004 
Email:  evans972@umn.edu 
 
Linda Hanson DC, MS, CCRP 
Study Coordinator and Co-Investigator 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (612) 626-6477 
Email: hans4236@umn.edu 
 
Brent Leininger, PhD, DC, MS 
Co-Investigator 
Earl E. Bakken Center for Spirituality & Healing 
University of Minnesota, Mayo Memorial Building C504 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (612) 301-9007 
Email: lein0122@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 
Phone: (612) 301-9003 
Email: schu1385@umn.edu 
 
Clarence Shannon, MD 
Co-Investigator 
Department of Anesthesiology 
University of Minnesota, Mayo Memorial Building 
420 Delaware Street, Minneapolis, MN 55414 
Phone: 612-624-9990 
Email: cshannon@umn.edu 
 
Joyce Wahr, MD 
Co-Investigator 
Department of Anesthesiology 
University of Minnesota, Mayo Memorial Building 
420 Delaware Street, Minneapolis, MN 55414 
Phone: (612) 624-9990 
Email: jawahr@umn.edu 
 
University of Pittsburgh-Clinical Coordinating Center 
Anthony Delitto PhD, PT, FAPTA 
Principal Investigator, Clinical Coordinating Center 
School of Health and Rehabilitation Sciences 
University of Pittsburgh 
4029 Forbes Tower, Pittsburgh, PA 15260 

 
 
PACBACK Protocol V8 page 13 
      
Phone: (412) 383-6560 
Email: delitto@pitt.edu 
 
Carol Greco, PhD 
Co-Investigator 
Department of Psychiatry 
University of Pittsburgh School of Medicine 
580 S. Aiken Avenue, Suite 310 
Pittsburgh, PA 15232 
Phone: (412) 623-3023 
Email: grecocm@upmc.edu 
 
Mike Schneider, DC, PhD 
Co-Principal Investigator, Clinical Coordinating Center 
School of Health and Rehabilitation Sciences 
University of Pittsburgh Bridgeside Point 1 
100 Technology Drive, Suite 500, Pittsburgh, PA 15219 
Phone: (412) 383-6640 
Email: mjs5@pitt.edu 
 
Ronald M. Glick, MD 
Co-Investigator 
Associate Professor, Departments of Psychiatry and  
Physical Medicine & Rehabilitation 
University of Pittsburgh School of Medicine 
580 S. Aiken Avenue, Suite 310 
Phone: (412) 623-1611 
Email: glickrm@upmc.edu 
                                         
University of Washington-Data Coordinating Center 
Patrick Heagerty, PhD, MS  
Principal Investigator, Data Coordinating Center 
School of Public Health, Department of Biostatistics 
Box 357232, 1959 NE Pacific Street, Seattle, WA 98195 
Phone: (206) 616-2720 
Email: heagerty@u.washington.edu 
 
Dennis Turk, PhD 
Co-Investigator 
Department of Anesthesiology & Pain Medicine 
Box 358045, Seattle, WA 98195 
Phone: (206) 543-2673 
Email: turkdc@uwashington.edu 
 
Duke University 
Steven George PT, PhD 
Co-Investigator 
Duke Orthopaedic Surgery 
8020 North Pavilion, Durham, NC 27705 
Phone: (919) 245-8992 
Email:steven.george@duke.edu      

 
 
PACBACK Protocol V8 page 14 
      
Francis Keefe, PhD 
Co-Investigator  
Department of Medicine 
2200 W Main St., Suite 340, Durham, NC 27705 
Phone (919) 416-3400 
Email: keefe003@mc.duke.edu 
 
University of North Texas Health Science Center 
John Licciardone, DO, MS, MBA 
Co-Investigator 
3500 Camp Bowie Blvd. 
Fort Worth, Texas 76107 
Phone: (817)-735-2028 
Email: john.licciardone@unthsc.edu 
 
Oregon Health & Science University 
Roger Chou, MD 
Co-Investigator 
OHSU Division of General Internal Medicine 
3181 SW Sam Jackson Park Road L475 
Portland OR 97239-3098 
Phone: (503)-494-6551 
Email: chour@ohsu.edu 
 
National Center for Complementary and Integrative Medicine/National Institutes of Health 
 
Pete Murray PhD 
Program Officer 
Program Director, Clinical Research in Complementary and Integrative Health Branch 
National Center for Complementary and Integrative Health (NCCIH) 
Phone: 301-496-4054 
Email: peter.murray@nih.gov 
 
Wendy Weber, ND, PhD, MPH 
Project Scientist 
Branch Chief, Clinical Research in Complementary and Integrative Health Branch 
Division of Extramural Research, NCCIH 
6707 Democracy Boulevard II, Suite 401, Bethesda, MD 20892 (Courier Service - 20817) 
Phone: 301-402-1272 
Email: weberwj@mail.nih.gov 
 
Qilu Yu, PhD 
Statistician 
Office of Clinical and Regulatory Affairs 
National Center for Complementary and Integrative Health (NCCIH) 
6707 Democracy Boulevard II, Suite 401, Bethesda, MD 20892 (Courier Service - 20817) 
Email: qilu.yu@nih.gov 
 

 
 
PACBACK Protocol V8 page 15 
      
PRÉCIS  
Study Title  
Spinal Manipulation and Patient Self-Management for Preventing Acute to Chronic Back Pain 
(PACBACK)              
 
Objectives  
Primary Objective 
Our long-term objective is to reduce overall lower back pain (LBP) burden by testing scalable first-line 
non-pharmacologic strategies that address the biopsychosocial aspects of acute/sub-acute LBP and 
prevent transition to chronic LBP (cLBP). We will assess the effectiveness of Spinal Manipulation 
Therapy (SMT), Supported Self-Management (SSM), and SMT+SSM relative to Medical Care (MC). 
 
Secondary Objective 
To facilitate translation and dissemination across health professions and other clinical settings we will 
gather contextual data using mixed methods guided by the Reach, Effectiveness, Adoption, 
Implementation, and Maintenance (RE- AIM) framework. Qualitative data will lend context regarding 
patients’, staff, providers’ and health system leaders’ perceptions of barriers and facilitators associated 
with the interventions; quantitative data collection will provide insight into intervention application, 
adherence, fidelity, and provider confidence.  
 
Design and Outcomes  
 
This is multi-site, predominantly pragmatic, phase III randomized trial using a 2x2 factorial design. 
Participants will be randomized to one of the following treatment groups: (1) SMT, (2) SSM, (3) the 
combination of SMT+SSM, or (4) MC. Physical therapists (PTs) and chiropractors (DCs) will deliver 
SMT and SSM, and medical providers will deliver the MC. The study has 2 primary effectiveness 
research questions with different time frames: 
 
1. Prevention of cLBP at 12 months as measured by LBP Impact (from Promis-29) scale: 8-50 
(Analysis of AUC for months 10-12) 
 
2. Average pain intensity and low back disability over 1 year as measured by weekly NRS and 
monthly RMDQ scores. 
 
Secondary outcome measures include: recovery, NIH minimal dataset including the Patient Reported 
Outcome Measurement Information System-29 (PROMIS-29) and other measures of LBP burden (e.g., 
productivity loss, health care and medication use, including opioids). 
 
Interventions and Duration  
All participants will be followed for 12 months after randomization. The initial treatment period is 8 
weeks. Decisions regarding visit frequency will be made collaboratively by the provider and participant, 
as is typical in real-world stings. Participants will be required to attend ≥ 75% of the prescribed 
intervention visits to be considered compliant. In addition, participants have the option to receive 
additional treatment in the group to which they were randomized if they experience a recurrence of an 
acute LBP episode during the 10-month follow-up period. Specifically, if the patient experiences a 
recurrence of bothersome low back pain (e.g., a “flare up” lasting more than two weeks) the provider will 
assess the patient and decide if additional visits are necessary over the 12 month research study.  
 

 
 
PACBACK Protocol V8 page 16 
      
Sample Size and Population  
A total of 1000 patients age 18 and above will be enrolled with nonspecific LBP of 2-12 weeks duration, 
at medium or high risk of developing cLBP. The randomization will use 2 strata: Site and Risk of 
chronicity (medium or high). 
1. STUDY OBJECTIVES 
The US is in the midst of an unprecedented pain management crisis, with chronic pain impacting more 
Americans than heart disease, diabetes, and cancer combined.1 Low back pain (LBP) is the most common 
chronic pain condition in adults and one of the leading cause of disability worldwide.2-4 Evidence based 
guidelines have recommended non-pharmacological treatments like spinal manipulation and behavioral 
approaches for LBP for nearly a decade,5 however uptake in practice has been poor. Further, little is 
known about the role of these treatments in secondary prevention of chronic LBP (cLBP), especially for 
patients with biopsychosocial risk factors. With burgeoning costs of cLBP and mounting evidence of 
ineffectiveness and harms of commonly used drug treatments, including opioids,6-8 there is a critical need 
for research on non-pharmacological treatments for cLBP prevention that can be readily translated to 
practice. 
 
Our long-term objective is to reduce overall LBP burden by testing scalable first-line non-pharmacologic 
strategies that address the biopsychosocial aspects of acute/sub-acute LBP and prevent transition to cLBP. 
We will assess the effectiveness of Spinal Manipulation Therapy (SMT), Supported Self-Management 
(SSM), and SMT+SSM relative to Medical Care (MC) in a randomized trial using a 2x2 factorial design. 
A total of 1000 patients will be enrolled with nonspecific LBP of 2-12 weeks duration, at medium and 
high risk of developing cLBP using the Subgroups for Targeted Treatment (STarT) Back Screening Tool 
(SBST). Physical therapists (PTs) and chiropractors (DCs) will deliver SMT and SSM, and medical 
providers will deliver the MC. This multi-site, predominantly pragmatic, phase III trial has two main 
objectives: 
 
1.1 
Primary Objective 
 
EFFECTIVENESS will be determined via three primary outcomes measures: 
 
1. Prevention of cLBP that is impactful at 10-12 months follow-up (8-50, LBP Impact scale using 
mean from months 10-12). The LBP impact scale includes measures of pain intensity, pain 
interference, and physical function from the PROMIS-29 Profile v2.0) 
2. Average pain intensity over 12 months post-randomization (0-10 numerical rating scale (NRS)) 
3. Average disability over 12 months post-randomization (0-24 scale, Roland Morris Disability 
Questionnaire (RMD)) 
 
Our hypotheses are informed by our prior research.7 9-23 Hypothesized quantifiable differences are 
outlined in the statistical considerations section.  
 
Secondary effectiveness objectives will assess: a) secondary outcomes including but not limited to 
recovery, the Patient Reported Outcome Measurement Information System-29 (PROMIS-29), and other 
measures of LBP burden (e.g., productivity loss, health care and medication use, including opioids); b) 
primary outcomes in pre-specified subgroups of acute vs. sub-acute and medium vs. high risk of cLBP 
using the SBST; and c) the effect of key psychosocial mediators on primary outcomes. 
 

 
 
PACBACK Protocol V8 page 17 
      
1.2 
Secondary Objective 
IMPLEMENTATION data related to the SMT, SSM, and SMT+SSM interventions will be collected 
and described using mixed methods about important influences that could affect future implementation 
and interpretation of results.24 Qualitative data will lend context regarding patients’, staff, providers’ and 
health system leaders’ perceptions of barriers and facilitators associated with the interventions; 
quantitative data collection will provide insight into intervention application, adherence, fidelity, and 
provider confidence. This will inform the dissemination and implementation plan championed by an 
experienced, multidisciplinary team, uniquely suited to facilitate translation across health professions. 
 
For implementation, we will gather contextual data using mixed methods to facilitate later translation to 
other real-world clinical settings, and aid in the interpretation of trial results. This aim is guided by the 
Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE- AIM)25 framework. It serves as a 
complement to PRECIS26 in providing richer information regarding potentially important influences on 
the effectiveness of the intervention from patient, staff, provider, and health system leadership 
perspectives.25 
 
The trial will use a two-phased approach. An initial UG3 planning and pilot phase will include 
development of the detailed study protocol, the data safety & monitoring plan, the Study Accrual and 
Retention Plan, obtaining IRB approval, and training of study staff and providers. In addition, during the 
UG3 planning and pilot phase 92 participants were enrolled into the trial to assess performance 
milestones focused on key areas of recruitment, enrollment, patient intervention adherence, provider 
intervention fidelity, and data collection. Criteria for including the 92 participants from the pilot phase as 
part of the total sample size were met, and the subsequent UH3 phase will enroll an additional 908 
participants. (See section 3.6.2 for further detail).  
2. BACKGROUND AND RATIONALE 
2.1 
Background on Condition, Disease, or Other Primary Study Focus 
The United States is in the midst of an unprecedented pain management crisis, with chronic pain 
impacting over ⅓ of the US population, and affecting more individuals than heart disease, diabetes, and 
cancer combined.1 27 With mounting concerns about the efficacy of commonly used pain interventions,28 29 
and estimated pain-related costs of $560 to $635 billion per year,1 the prevention of chronic pain has 
become one of the most significant public health challenges of our time. While preventing chronic pain 
could result in huge public health benefits, there has been scant research focused on interventions 
targeting the secondary prevention of pain and the transition from acute to chronic.30 
  
This research aligns with the National Center for Complementary and Integrative Health’s (NCCIH) 
Strategic Plan 201631 by focusing on the investigation of non-pharmacologic pain management strategies 
that can improve first-line LBP management, including the reduction of opioid use. Specifically, this 
large, pragmatic study addresses the secondary prevention of cLBP, the most common chronic pain 
condition in American adults.2 
  
LBP is one of the most common and burdensome pain conditions worldwide with an estimated 40-80% of 
adults experiencing LBP at some point in their lives.32 33 LBP related disability has increased an alarming 
42% over the past two decades, making it the leading cause of disability globally.4 Approximately 20% of 
acute cases will become chronic,34 and it is these individuals that bear a disproportionate share of LBP 
associated burden.35 Spinal pain accounts for 9% of total US healthcare expenditures 8 and costs US 
employers an estimated $19.8 billion per year due to lost productivity.36 While there is a wide range of 
treatments available for LBP, the majority of cases are not optimally managed.37 There is also a growing 

 
 
PACBACK Protocol V8 page 18 
      
awareness that primary care physicians are under-trained in pain management, and do not have ready 
access to interdisciplinary treatments that could address LBP from a biopsychosocial perspective.38 This 
is evidenced by the persistent use of marginally effective and potentially harmful therapies that largely 
ignore the psychosocial aspects of LBP. For example, the use of epidural injections, opioid prescriptions, 
and spinal surgeries for LBP has doubled over the past decade with little positive impact on patient 
outcomes.28 39 Of growing concern, is the over reliance on opioids. An estimated 40% of LBP patients use 
opioids making them the most commonly prescribed medications for LBP.35 40 This occurs despite LBP 
guidelines suggesting other pharmacologic and non-pharmacologic treatment options 5 and mounting 
recognition of opioid misuse, addiction, and fatal overdose.6 The recently released AHRQ review41 
largely confirmed the main conclusions of previous reviews42 regarding the benefits and harms of 
pharmacologic therapies. For acute or subacute LBP, NSAIDs, opioids, and skeletal muscle relaxants 
were associated with only small effects for pain compared to placebo; no benefits were found for systemic 
corticosteroids or acetaminophen (which due to new evidence, differed from previous reviews). There 
was also increased risk of adverse events (AEs) compared to placebo for all pharmacological therapies. 
 
The overreliance on ineffective, costly and at times harmful treatments suggests a serious deficiency in 
the uptake and translation of research based guidelines.43-45 The 2017 American College of Physicians 
LBP guidelines recommended clinicians select non-pharmacologic treatments including spinal 
manipulation for acute LBP and consider pharmacological treatment if desired.46 Poor adherence to 
research based guidelines is endemic across health professions.47 There are several barriers to research 
uptake at physician and health system levels including knowledge deficiencies,48-50 poorly aligned 
incentives,51 and organizational factors.52 53 There is also recognition that most research has been 
insufficiently pragmatic to meet the needs of its end-users.24 To speed the translation of research to 
practice there has been increasing interest in research designs and strategies that work to balance 
methodological rigor with generalizability. This includes the emergence of hybrid effectiveness-
implementation designs,24 and other frameworks,25 26 which blend rigorous clinical research approaches 
alongside implementation research methods to facilitate adoption by providers and systems. While such 
approaches are gaining traction in other health fields,54-56 there have been few studies in the LBP arena57 
which have used such an approach. 
 
There is growing evidence that physical and psychosocial risk factors can predict progression of acute 
LBP to chronic.34 58 This has led to recommendations for trials to focus enrollment on participants at 
higher risk of chronicity, limiting the testing of interventions to those in need, and excluding those with a 
more favorable natural history.30 There is also evidence that treatments addressing psychosocial risk 
factors in patients with increased risk of chronicity are more effective than usual care.59 However, most 
clinical trials to date on acute and subacute LBP populations have tested interventions irrespective of 
prognosis, limiting the ability to make confident conclusions about their effectiveness.30 Consequently, 
there is a need for research that can more rigorously assess the potential of promising interventions to 
prevent acute LBP from progressing to chronic by appropriately targeting those at higher risk.  
 
To reduce cLBP burden, patients should have greater access to front-line care addressing both their 
physical and psychosocial needs. This will require the integration of psychosocial interventions with 
traditional biologically based pain management approaches.60 Physical therapists (PTs) and chiropractors 
(DCs) are the most common providers of non-pharmacologic treatment for LBP in the U.S., with 
approximately 39% of LBP patients seeking treatment from DCs and 34% from PTs.40 Both PTs and DCs 
help patients manage symptoms and aid in the restoration of movement and functional ability. They are 
thus well suited to integrate psychosocial strategies with biological/physical approaches,60 61 and play an 
essential role in the frontline management of LBP.62 63 
 

 
 
PACBACK Protocol V8 page 19 
      
2.2 
Study Rationale 
2.2.1 Preliminary Studies 
Collectively, the investigative team has experience conducting multi-site, comparative effectiveness 
studies. Findings from their research have informed several aspects of the study design including 
recruitment and enrollment,10-12 64-66 risk stratification,67 intervention design,10-16 18-22 64 68 and mixed 
methods data collection.69-71 Their research has also demonstrated that SMT, SSM (incorporating several 
evidence based behavioral elements), and their combination, are viable treatment options for LBP in 
different populations.9-12 14-16 18-22 64 66 68 72  
 
Further, investigators Bronfort, Delitto, Chou, George, Licciardone, Schneider, and Turk are actively 
involved in a broad range of influential professional activities. These have helped prioritize the research 
questions most relevant to health professions involved in LBP care delivery, and enhance the likelihood 
of future translational success. This involves participation on the NIH LBP Task Force,73 Initiative on 
Methods, Measurement, and Pain Assessment in Clinical Trials group (IMMPACT),30 74-81 Analgesic, 
Anesthetic, and Addiction Clinical Trials, Translations, Innovations, and Opportunities Network 
(ACTTION), public-private partnership with the FDA,79 82-87 and physician,5 physical therapy,17 
osteopathic,88 chiropractic,89 and cross-disciplinary guidelines6 23 41 42 90 and systematic reviews.41 91-94 
Cumulatively, the investigators’ research findings and professional experiences have contributed 
substantially to the design of the study and enhance the likelihood of successful project completion and 
effective dissemination. 
 
2.2.2 Interventions 
The study uses several approaches to enhance the likelihood of advancing LBP research and shifting the 
sub-optimal management of acute and sub-acute LBP that currently exists in primary care. 
 
1)  This study is the first to assess the effectiveness of SMT, SSM and SMT+SSM relative to MC for the 
secondary prevention of cLBP that is impactful.  
 
2)  The comprehensive quantitative data collection throughout the follow-up year addresses several 
currently unanswered questions regarding the treatment of acute LBP. This includes how SMT, SSM, and 
SMT+SSM affect time to recovery from acute LBP, the trajectory of pain and disability over time, as well 
as the effects of and impacts on psychosocial outcomes. 
 
3)  We will address both effectiveness and implementation within our trial. We consider this an efficient, 
low risk, and potentially high yield tactic, which maintains the rigor required for assessing effectiveness,26 
while simultaneously adding key contextual information to speed implementation to other real-world 
settings.25 
 
4)  By training both DCs and PTs to deliver SSM (either alone or in combination with SMT) there is 
potential for these providers to have a larger and more impactful role in the frontline management of LBP. 
This may shift the current clinical practice paradigm away from an over-reliance on opioids and other 
marginally effective medications, to accessible and integrated biopsychosocial approaches. 
 
5) This study will be the first in the U.S. to involve collaboration between influential researchers from 
medicine, psychology, and all three licensed provider groups of SMT (chiropractic, physical therapy, and 
osteopathy), increasing the likelihood of widespread translational success. 
 
Spinal manipulation therapy (SMT) is a physical modality used by both DCs and PTs and is well 
accepted by patients as indicated by relatively high utilization and patient satisfaction relative to usual 

 
 
PACBACK Protocol V8 page 20 
      
medical care.95 Further, the American College of Physicians and the American Pain Society highlight 
SMT as one of the recommended non-pharmacologic therapies for acute and sub-acute LBP.46 
 
The recently released Agency for Health Research and Quality (AHRQ) comparative effectiveness review 
provides the most up-to-date synthesis of research regarding SMT for acute LBP.41 This review builds 
upon a 2012 Cochrane systematic review,64 96-98 plus three additional trials that have been published 
since.64 97 98 The AHRQ review found some evidence that SMT is associated with beneficial effects for 
acute LBP compared to sham therapy, no intervention, or usual medical care.41 Importantly, the side 
effects associated with SMT are overall benign, with approximately 50% of patients reporting one 
reaction, most commonly local discomfort which resolves within a day.99-102 There is stronger evidence 
supporting the use of SMT in cLBP populations where patients have more complicated physical and 
psychological phenotypes.103 This provides a rationale for applying SMT early during the clinical course 
of patients with increased risk of chronicity based on physical and psychosocial risk factors (e.g., leg pain, 
comorbid pain, catastrophizing, fear, anxiety, and depression).104 
 
Overall, SMT’s low risk profile and evidence of benefit lend support for it to be better integrated into 
primary care settings in an effort to diminish reliance on pharmacologic and other more invasive 
treatments for acute and sub-acute LBP. It is noteworthy that most studies assessing SMT for acute and 
sub-acute LBP have primarily assessed pain and disability outcomes in the short-term. In light of the 
enormous burden imposed by LBP of longer duration, a more relevant question appears to be, “Can SMT 
prevent acute and sub-acute LBP from transitioning to chronic?” Sufficiently large, adequately powered 
studies are needed to address this very timely and important issue.96 
 
Supported Self-management (SSM). Self-management is widely advocated for LBP and other pain 
conditions.1 5 We have adopted the definition proposed by Carnes et al,105 which is consistent with the 
study and application of self-management for other musculoskeletal pain conditions.106-108 Defined as a 
structured or semi-structured instructional program, self-management includes multiple, distinct 
components aimed at improving patients’ ability to effectively care for themselves on a daily basis.105 
Components can include psychological strategies (e.g., behavioral or cognitive); mind-body approaches 
(including relaxation, meditation or guided imagery); physical activity (e.g., exercise); lifestyle advice 
(e.g., for sleep, daily activities, social support); and pain education (e.g., pain theories, prognosis, and 
pain management tips).105 While patients recognize the need for self-management strategies for pain, 
often they need the support and validation of health care providers to initiate and maintain optimal self-
care.109 110 In light of increasing calls for PTs and DCs to play a larger role in addressing the psychosocial 
aspects of LBP, a natural avenue is through structured self-management (SSM), using evidence-based 
behavioral strategies that educate, motivate and support patients. 
 
The most recent AHRQ review by Chou et al, found psychological/behavioral based strategies, as well as 
psychological approaches with exercise, yielded small to moderate benefits for cLBP; insufficient 
evidence however was available to determine effects in patients with acute LBP.41 These findings are 
similar to systematic reviews for other chronic musculoskeletal pain conditions which have found 
behavioral based strategies to be beneficial;111 112 importantly, patient education on its own has been found 
to be insufficient.113 114 Further, there is some evidence that shorter programs (no longer than 8 weeks), 
and delivery by health professionals (versus lay persons) are effective.105 Research has shown that 
healthcare providers other than psychologists can be trained to confidently deliver SSM programs similar 
to the one proposed.106 108 115 
 
While most research to date has focused on SSM for chronic pain management, acute suffers are also 
likely to benefit from cognitive and behavioral skills for pain management. To this end, a noteworthy 
review by Brunner et al, found that a form of cognitive behavioral therapy, is a promising strategy that 
can be integrated into ambulatory PT practices for the prevention of cLBP.61 This suggests that by 

 
 
PACBACK Protocol V8 page 21 
      
addressing the very psychosocial factors implicated in pain (e.g., fear avoidance, social isolation, etc.) 
well-delivered SSM programs for acute and sub-acute LBP patients could play an important role in cLBP 
prevention, and therefore warrant further study. 
 
Rationale for combining SSM and SMT: Consistent with NCCIH’s strategic objective to examine the 
interactions of non-pharmacologic interventions for additive effects,31 the research will examine the 
effectiveness of combining SSM and SMT. Historically, the predominant part of a PT and DC practice 
has focused on the biological or physical aspects of LBP,60 with a separation of mind and body, and 
consequently a distinction between physical and psychological treatments.116 117 However, the 
biopsychosocial model suggests a shift away from this dualism.116 There is an opportunity to advance 
LBP care by exploring how PTs and DCs (and others) can play a role in addressing the complex factors 
implicated in the transition to LBP chronicity.109 110 118 As noted above, patients with increased risk of 
chronicity have different combinations of physical and psychosocial obstacles to recovery.104 Given that 
SMT and SSM target complementary mechanisms (SMT primarily biological and physical, and SSM 
primarily psychological and social), we anticipate that the combination will promote LBP recovery and 
prevent LBP chronicity to a greater degree than usual medical care or either monotherapy alone. Further, 
there are pragmatic advantages to having both treatments delivered by a single practitioner, particularly 
DCs and PTs, including improved accessibility and integration.106 Findings from a recent study by the 
investigators demonstrated the addition of SMT to home exercise and advice (incorporating several 
behavioral elements included in the SSM) reduced pain and disability in adults with back-related leg 
pain.11 
 
Medical Care (MC) The medical care treatments are informed by the American College of Physicians 
guidelines on noninvasive treatment for LBP46 and reflect what is delivered in primary care clinics. 
Medical care will be provided by licensed physicians or advanced practice nurses with a minimum of 3 
years managing musculoskeletal pain patients. Decisions regarding medical care (e.g., pharmacological 
management) and visit frequency will be made collaboratively by the provider and patient, as normally 
occurs in clinical practice. Care will be provided within research clinics, outpatient clinics, or virtually 
using HIPAA compliant Zoom, affiliated with the Universities of Pittsburgh and Minnesota.  
3. STUDY DESIGN 
3.1 Trial design 
This is a two-site randomized trial with a 2x2 factorial design. A total of 1000 individuals with acute or 
subacute non-specific LBP, at medium or high risk for persistent disabling LBP, will be randomized to 
either SMT, SSM, SMT+SSM, or MC . The trial uses a hybrid design to address both effectiveness and 
implementation.24  
 
The PRECIS-2 tool has been used to guide the description of the study design and provide clarity 
regarding the pragmatic and explanatory features of the study.26 This hybrid study design can best be 
characterized as rather pragmatic. By design, there will be no attempt to control for non-specific effects 
due to intervention group differences in time and attention. 
  
Specific design features that are very pragmatic include: 
● use of outcomes that are patient-oriented 
● use of all data in an intention to treat analysis 
  
Specific design features that are close to or equally pragmatic and explanatory include: 
● broad inclusion and narrow exclusion criteria within the subgroup at increased risk of chronicity 
● expanded recruitment from the general population and clinical settings 

 
 
PACBACK Protocol V8 page 22 
      
● conduct in outpatient research clinics 
● minimal additional resources to organize and deliver the interventions with the exception of SSM 
training 
● flexibility in experimental and comparator intervention delivery 
● methods to ensure patient compliance with interventions 
 
Specific design feature that is very explanatory include: 
● close follow-up of participants monthly for one year 
 
 
 
 
 
 
Table 3.1 – PRECIS-2 Domain Definition 
Domain 
Criteria 
Eligibility 
To what extent are the participants in the trial similar to those who would receive this 
intervention if it was part of usual care? 
Recruitment 
How much extra effort is made to recruit participants over and above what would be 
used in the usual care setting to engage with patients? 
Setting 
How different are the settings of the trial from the usual care setting? 
Organization 
How different are the resources, provider expertise, and the organization of care 
delivery in the intervention arm of the trial from those available in usual care? 
Flexibility 
(delivery) 
How different is the flexibility in how the intervention is delivered and the flexibility 
anticipated in usual care? 
1
2
3
4
5
Eligibility
Recruitment
Setting
Organization
Intervention
Flexibility
Intervention
Adherence
Degree of
Follow Up
Relevance of
Primary
Outcome
Primary
Analysis
Figure 3.2.  Mapping to PRECIS-2 Domains
(scores: 5=fully pragmatic, 1= fully 
explanatory)

 
 
PACBACK Protocol V8 page 23 
      
Flexibility 
(adherence) 
How different is the flexibility in how participants are monitored and encouraged to 
adhere to the intervention from the flexibility anticipated in usual care? 
Follow-up 
How different is the intensity of measurement and follow-up of participants in the 
trial from the typical follow-up in usual care? 
Primary outcome 
To what extent is the trial’s primary outcome directly relevant to participants? 
Primary analysis 
To what extent are all data included in the analysis of the primary outcome? 
 
 
3.2 Primary and secondary outcomes 
Primary and secondary outcomes will be collected predominantly using web-based self-report tools (for 
details see section 6.1 Schedule of Evaluations and section 10 Data Collection & Quality Assurance).  
 
Primary effectiveness outcome measures are: (1) prevention of cLBP that is impactful at 10-12 months 
follow-up (LBP impact from the PROMIS-29 Profile v2.0); (2) average pain intensity over 12 months 
post-randomization (pain, numerical rating scale); (3) average low back disability over 12 months post-
randomization (Roland-Morris Disability Questionnaire). Secondary outcomes include: recovery, 
PROMIS-29 Profile v2.0 measures to assess pain interference, physical function, anxiety, depression, 
fatigue, sleep disturbance, and ability to participate in social roles and activities. Other patient-reported 
measures include LBP frequency, medication use, healthcare utilization, productivity loss, STarT Back 
screening tool status, patient satisfaction, prevention of chronicity, adverse events, and implementation 
measures. Objective measures include the Quebec Task Force Classification, Timed Up & Go Test, the 
Sit to Stand Test, and the Sock Test assessed by clinicians blinded to the patients’ intervention 
assignment. 
 
Prevention of chronic LBP will be measured using the patient-rated LBP impact measure described by 
the NIH RTF73 which is a quantitative measure derived from subsets of the PROMIS-29. It is scored on 
a scale of 8-50 (8-27: Mild; 28-34: Moderate and >34: Severe). We will measure LBP Impact on a 
monthly basis using the area under the curve for Month 10-12 as the primary endpoint. 
 
There is evidence on reliability, validity, and responsiveness and its prognostic value to support the use 
of the impact measure. (Dutmer 2019)  
 
Important note: The chronic LBP impact measure was collected as a secondary outcome measure from 
the start of the trial but was adopted as a primary outcome in July 2021 with approval from the trial 
DSMB and by NIH. At the time of the change in primary endpoint less than 25% of the total participants 
had been recruited into the trial.  Under the supervision of the data coordinating center no interim 
analysis was planned or conducted and none of the investigators have had access to outcomes data. 
 
When recruitment in the UG3 phase started in October 2018 we were using the published NIH RTF new 
definition of chronic LBP: “a back pain problem that has persisted at least 3 months and has resulted in 
pain on at least half of the days in the past 6 months.” Specifically, this will be assessed with two NIH 
RTF minimum dataset items: 1) LBP duration and 2) proportion of days that LBP has been a problem 
over the past 6 months.97  The chronicity status at 12-month follow-up is based on patients’ recall of their 
low back pain being present on more or less than half the days during the preceding 6 months.  
 
Since the initial approval and funding of our project by NCCIH in August 2017, important published 
information has been accumulating regarding the importance of measuring the impact of chronic pain 

 
 
PACBACK Protocol V8 page 24 
      
including chronic LBP73 (von Korff 2020, Herman 2019, Dahlhamer 2018, Dutmer 2019, Pitcher 2019). 
This body of literature prompted us to reevaluate the adequacy of our primary chronicity outcome 
measure. We were aware that the original NIH RTF chronicity outcome measure has several recognized 
limitations: It is a dichotomous outcome that does not incorporate pain severity, pain interference with 
daily activities, limitations of physical function, and is not able to quantitatively overall LBP impact. It 
also has limited statistical power to conduct pre-specified pairwise comparisons among the four groups. 
To date no data in the literature is available on the prevalence LBP chronicity using the RTF definition. 
The chronicity status at 12-month follow-up based on patients’ recall of their low back pain being present 
on more or less than half the days during the preceding 6 months.  
 
References in paragraphs above on this page: 
Dahlhamer 2018 - Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults — United 
States, 2016. MMWR Dahlhamer J, Lucas J, Zelaya, C, et al. Morb Mortal Wkly Rep 2018;67:1001–
1006. 
 
Dutmer 2019 - The NIH Minimal Dataset for Chronic Low Back Pain Responsiveness and Minimal 
Clinically Important Change Dutmer, A, Reneman, M, Schiphorst Preuper, H et al. SPINE: October 15, 
2019 - Volume 44 - Issue 20 - p E1211-E1218 
 
Herman 2019 -  Exploring the prevalence and construct validity of high-impact chronic pain across 
chronic low-back pain study samples Patricia M.Herman, Nicholas Broten et al. The Spine Journal 
Volume 19, Issue 8, August 2019, Pages 1369-1377 
 
Pitcher 2019 - Prevalence and profile of high-impact chronic pain in the United States  MH Pitcher, M 
Von Korff, MC Bushnell, L Porter - The Journal of Pain, 2019 Volume 20, Issue 2, February 2019, Pages 
146-160 
 
Von Korff 2020 - Graded chronic pain scale revised: mild, bothersome, and high impact chronic pain 
M Von Korff, LL DeBar, EE Krebs, RD Kerns, RA Deyo et al. Pain,  March 2020 - Volume 161 - Issue 3 
- p 651-661  
 
 
3.3 Study location 
The University of Minnesota (UMN) and the University of Pittsburgh (UPITT) will serve as the Clinical 
Coordinating Centers (CCC), with the UMN serving as the primary institution providing overall project 
coordination. The University of Washington (UWA) will serve as the Data Coordinating Center (DCC). 
Screening of potential study candidates and treatment of enrolled participants will be coordinated by the 
CCCs and will occur at University-affiliated research, outpatient clinics, or virtually using HIPAA 
compliant Zoom.  
 
3.4 Intervention administration 
SMT, SSM, and SMT+SSM will be provided by PTs and DCs in Pittsburgh and in Minnesota. Medical 
providers will provide MC. Since the PTs and DCs will follow the same treatment protocols, there is no 
need or plan to assess differences in outcomes based on provider type. The primary goal of SMT is to 
address the biological and physical aspects of LBP (e.g., spinal dysfunction) with the intention of 
restoring maximum movement and functional ability of the spine. The goals of SSM are to primarily 
address the psychosocial aspects of acute and sub-acute LBP, by providing patients the opportunities to 
develop their capacity and motivation to self-manage their LBP in an adaptive manner.108 121 The goals of 
the MC group will be to provide care for acute and subacute LBP using evidence based guidelines for 
primary care.  
 

 
 
PACBACK Protocol V8 page 25 
      
3.5 Randomization, stratification, and blinding 
Patients will be randomized to one of the following treatment groups within the 2x2 factorial design: (1) 
SMT, (2) SSM, (3) the combination of SMT+SSM, or (4) MC. From January 2021 to October 2021, 
patients were randomized to remote-delivery of (1) SSM or (2) MC due to the COVID-19 pandemic. 
 
The DCC will perform blocked randomization (using variable block sizes of 12 or 16) following 
stratification by site and baseline risk for cLBP according to the SBST (medium or high). The computer-
generated random assignments will be conveyed electronically from the DCC to each clinical site. 
 
Blinding of treatment providers and participants is not feasible. However, the following steps will be 
taken to minimize potential bias and enhance study rigor: a) all study personnel involved in screening and 
enrollment will be masked to upcoming randomization assignments; b) all study personnel involved in 
outcome assessment will be independent of intervention delivery, blinded to intervention arm, and trained 
in ensuring unbiased data collection until after database lock; c) only a single member from the DCC will 
be unblinded and have access to treatment group assignment for the purpose of creating closed DSMB 
reports; and d) participants will be queried in self-report questionnaires as to whether or not anybody 
attempted to influence their responses. 
 
3.6 Trial phases 
The trial will use a two-phased approach. An initial UG3 planning and pilot phase will include study 
start-up activities including completion of study related documents in collaboration with NCCIH (e.g., 
study protocol, data safety & monitoring plan), obtaining IRB approval, and training of study staff and 
providers. In addition, during the UG3 planning and pilot phase 92 participants were enrolled into the trial 
to assess performance milestones focused on key areas of recruitment, enrollment, patient intervention 
adherence, provider intervention fidelity, and data collection. The milestones and threshold criteria for 
transition from the UG3 planning and pilot phase to the main UH3 phase of the trial where the remaining 
908 participants will be enrolled are provided in section 3.6.1. In addition, the criteria for not including 
the UG3 phase participants in the main UH3 phase of the trial are provided in section 3.6.2.  
 
3.6.1 Milestones for transition from UG3 to UH3 
Table 3.2 -- Transition Milestones 
Milestone 
Milestone Description 
Expected Date of Completion 
CCC/DCC 
#1 
Develop and finalize UG3/UH3 NIH approved documents: 
-Study Accrual and Retention Plan (SARP); includes plans 
for women and minorities, adherence and retention (CCC) 
-Study Protocol (CCC) 
-Data & Safety Monitoring Plan; includes plan for SAE 
reporting (DCC) 
-Informed Consent Documents (CCC) 
Final NIH-approved documents for Protocol Review 
Committee (PRC) due by expected completion date. 
Prior to Pilot Study 
enrollment AND at least 6 
months prior to transition 
request 
 
For UG3 documents: First 
half of September, 2018 
approved to start (completed 
site initiation visit) 
CCC/DCC 
#2 
Obtain IRB approval; coordinate site approvals with 
central IRB for the UG3 pilot study. 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 

 
 
PACBACK Protocol V8 page 26 
      
CCC/DCC 
#3 
Finalization of NIH-approved case report forms. 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 
 
CCC #5/ 
DCC #11 
Develop and finalize Manual of Operations 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 
 
DCC #5 
Develop Study database and finalize data management and 
data quality plan. Version for PRC due by expected 
completion date 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 
 
CCC #6/ 
DCC#10 
Recruit and complete regulatory work and contracts at 4 
sites needed for the UH3 phase with high likelihood of 
adequate patient recruitment, retention, intervention 
delivery, and data quality (see Criteria for Transition 
below). 
A list of back up sites will be made available. IRB and 
other necessary approvals/contracts will be obtained for 
recruitment in all sites. 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 
 
CCC #7/ 
DCC #12 
Develop and finalize training and fidelity monitoring plans 
and materials. 
The CCC will assume responsibility for training material 
associated with screening and enrollment of subjects and 
completion of study procedures. The DCC will develop 
training materials for use of the research portal (study 
management and data collection). 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 
 
DCC #7 
Develop and finalize safety surveillance plan and site 
monitoring plan. 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 
CCC #8/ 
DCC #12 
Develop and finalize recruitment plan and patient 
recruitment materials. 
The CCC will assume responsibility for training, 
recruitment, and fidelity material associated with 
recruitment of subjects and completion of study 
procedures. 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 
 

 
 
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DCC #8/ 
CCC #9 
Develop ancillary study policy document. 
By date of transition request 
May 1, 2019 
 
DCC #9/ 
CCC#10 
Create an NIH-approved resource and data-sharing plan. 
By date of transition request 
May 1, 2019 
 
CCC #11/ 
DCC #15 
Submit transition request for UH3 including: annual 
milestones, updated timeline, an updated detailed budget. 
By date of transition request 
May 1, 2019 
 
CCC #12/ 
DCC #14 
Update and finalize UH3 NCCIH/DSMB approved study 
documents: 
SARP 
Protocol  
DSMP  
ICF 
The CCC will assume primary responsibility for 
completion of the SARP, Study Protocol, and Informed 
Consent Document, while the DCC will assume the lead 
on completion of the Data & Safety Monitoring Plan. 
By date of transition request 
April 1, 2019 
CCC #13 
Meet additional threshold criteria for transition* (see 
separate table). 
By date of transition request 
May 1, 2019 
 
DCC #13 
Develop study web page / portal with links to participant 
screening, enrollment, randomization, and electronic data 
capture tools. 
Prior to Pilot Study 
enrollment: First half of 
September, 2018 AND by 
date of transition request May 
1, 2019 
 
 
Threshold Criteria for Transition (UG3 to UH3) 
Table 3.3  
Criteria 
(Indicator) 
Criterion Description 
Expected Date of Completion 
A 
(Clinical Sites) 
A total of 4 clinic sites (2 at UMN, 2 at UPITT) 
participate. 
By the end of the UG3 Pilot 
Study April 15, 2019 
B 
(Recruitment & 
Retention) 
Total of 80 participants are enrolled in the Pilot 
Study. 
By the end of the UG3 Pilot 
Study April 15, 2019  
 

 
 
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Reporting on available 
follow-up data for all 
participants will be provided 
at the time of transition 
request May 1, 2019.  
C 
(Recruitment & 
Retention) 
An average total of  ≥ 24 participants are enrolled per 
month in the two highest enrollment months of Pilot 
Study. 
By the end of the UG3 Pilot 
Study April 15, 2019 
D 
(Recruitment & 
Retention) 
≥85% of enrolled participants are retained for the 
primary outcome, measures of pain and disability at 
the 8 week time point. 
Note: chronicity at 1 year which is part of the primary 
outcome, cannot be assessed in the pilot study due 
time constraints. 
At the end of the 8-week 
intervention phase for all 
intervention groups in the 
entire 80 participants 
enrolled in the UG3 Pilot 
Study 
E 
(Intervention 
Adherence) 
≥80% of enrolled participants engage in the assigned 
treatment (defined as attending ≥75% of prescribed 
intervention visits). 
In the entire 80 participants 
enrolled in the UG3 Pilot 
Study 
F 
(Intervention 
Contamination) 
≤10% of participants cross contaminate defined as 
receiving unassigned intervention or part of 
unassigned intervention during the 8 week treatment 
phase (due to outside care, or provider contamination 
of the interventions, as measured on patient self-
report questionnaires). 
Within the 8 week 
intervention phase in the 
entire 80 participants 
enrolled in the UG3 Pilot 
Study 
G 
(Intervention 
Contamination) 
≤10% of audited visit records exhibit cross 
contamination defined as delivering unassigned 
intervention or part of unassigned intervention during 
the 8 week treatment phase (as measured on provider 
record). 
Within the 8 week 
intervention phase in the 
entire 80 participants 
enrolled in the UG3 Pilot 
Study 
H 
(Safety & 
Adverse Events) 
≤5% of participants experience an unexpected, 
related, moderate or greater adverse event. 
<2% SAE overall unexpected and related to the 
intervention (no more than 1 participant). 
In the entire 80 participants 
enrolled in the UG3 Pilot 
Study 
 
 

 
 
PACBACK Protocol V8 page 29 
      
3.6.2 Criteria for not including participants from UG3 in the UH3 analysis  
Study data from the UG3 pilot phase and the UH3 full-scale phase will be combined for analysis unless 
the UG3 planning and pilot phase leads to changes in the following: 
● Design (e.g., the addition or removal of a trial arm) 
● Inclusion/exclusion criteria (would apply to participants from the Pilot Study that would not 
qualify for the full-scale phase) 
● Outcome measures (e.g., the addition of outcome measures or timing of administration) 
● Interventions or their delivery (e.g., protocol modification of the interventions or type of provider 
delivering them) 
 
     NCCIH, and the DSMB reviewed and approved combining data for the UG3 and UH3 phases at the 
end of the UG3 phase. 
 
3.6.3 UH3 Phase disruption due to COVID-19 
In March 2020, the COVID-19 global pandemic resulted in a temporary suspension of the trial, including 
recruitment, enrollment, intervention delivery, and the collection of objective secondary outcomes. In 
response to increased severity of the COVID-19 pandemic, including increased rates of community 
spread, hospitalization and death rates and a rapidly changing environment, we made important 
modifications to the trial protocol.  
 
Two of the trial arms (SMT and SSM+SMT) required face-to-face contact with study participants. In 
order to avoid physical interaction, we updated the protocol to allow for remote assessments and 
interventions in a partial 2 group randomization period during which participants were randomized only 
to MC or SSM, delivered using HIPAA-compliant videoconferencing technology. In order to accomplish 
this, several modifications were made including: transitioning to an electronic consent process; updating 
study protocols and training staff to assess eligibility criteria, deliver SSM and MC virtually, and 
objective measures via telehealth; addition of secondary outcome measures regarding COVID-19 impact 
and telehealth usability; modifications to randomization scheme for the partial 2-group randomization 
period; and implementation of active COVID-19 monitoring at participating sites. The partial 2-group 
randomization period began in December 2020.  
 
In November 2021, when conditions were met to safely return to in-person activities, we returned to full 4 
group treatment allocation. Clinic activities that were suspended at UM Epidemiology Clinical Research 
Center due to COVID-19 were moved to the Berman Center for Outcomes and Clinical Research. In 
order to account for potential period-effects, we updated our statistical analysis plan to include an 
adjustment for partial randomization time periods in all analyses. Since November 2021, all trial 
procedures have been compliant with Covid mitigation rules (masking, distancing, and sanitation of 
surfaces) established by the Universities of Minnesota and Pittsburgh. All modifications were planned by 
the principal investigative team, reviewed and approved by the DSMB and the funding agency, and 
reported within the trial registration at ClinicalTrials.gov.  
 
 
3.6.3.1 Covid-19 Monitoring 
The DCC will proactively monitor local COVID related trends from the clinical sites’ recruitment 
catchment areas, including number of infections, and hospitalization and death rates. This information is 
used to guide decisions on trial conduct.  
 
3.7 Enrollment period and follow-up 
Participant enrollment will take approximately 4 months for the UG3 planning and pilot phase and 
approximately 4-5 years for the main UH3 phase of the trial. Individual participants will be followed on a 
weekly basis for 52 weeks from randomization. 

 
 
PACBACK Protocol V8 page 30 
      
4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 
Inclusion Criteria 
Participants must meet all of the following inclusion criteria: 
● 18 years of age or older prior to participating in study procedures. 
● At the time of randomization, the participant’s current episode/aggravation of LBP must be 
between 2 and 12 weeks duration.  
● Participants with no LBP or less than severe LBP on average in the month prior to the current 
episode/aggravation are eligible.  
● Average LBP severity ≥3 on the 0-10 numerical rating scale (NRS) over 7 days 
● Medium or High Risk for persistent disabling back pain according to the STarT Back screening 
tool 
● Ability to read and write fluently in English 
4.2 
Exclusion Criteria 
Candidates meeting any of the following exclusion criteria at baseline will not be enrolled: 
 
● Average LBP characterized as severe in the month preceding the current episode/aggravation 
● Specific non-mechanical causes of LBP (e.g., infection, cancer)  
● Contraindications to SMT or SSM (e.g,. spinal fracture, progressive neurological deficits, 
inflammatory arthropathies of the lower back, surgical fusion of lumbar spine) 
● Active management of current episode of LBP by another healthcare provider.  Participants must 
stop management with their current provider to enroll in the study (e.g., SMT, PT, prescription 
medication, CBT, a structured program led by a healthcare provider that may include pain 
education, mind-body practices, coping strategies etc).  
o Participants taking prescription opioid medication for LBP are required to obtain a note 
from a prescribing/medical provider to confirm they have safely discontinued their opioid 
medication.  
● Serious comorbid health condition that either requires medical attention (e.g., severe 
hypertension, inadequately managed serious mental health conditions, substance abuse), or has a 
risk for general health decline over the next year (e.g., Parkinson's disease, Multiple Sclerosis, 
organ failure, Dementia, Alzheimer's disease). 
● Pregnancy, current or planned, and nursing mothers during the study period.  
● Inability or unwillingness to give written informed consent. 
 
4.3 
Study Enrollment Procedures  
4.3.1 Recruitment methods 
Trial participants will be recruited from the Twin Cities (Minneapolis and St. Paul, MN), Pittsburgh, PA, 
and surrounding metropolitan communities using methods described in the Study Accrual and Retention 
Plan. These include identifying LBP patients at risk for developing cLBP from existing electronic health 
records, cultivating relationships with local providers (e.g., MDs, DCs, PTs) to obtain participant 
referrals, and distributing recruitment materials to participating health systems’ clinics and providers via 
regular communication channels (e.g., electronic and print mailings, social media). Additionally, we will 
use print mailings to targeted demographic groups, mass media advertisements (e.g., minority-oriented 
community newspapers), and we will work with minority leaders and groups in respective cities (e.g., 
Urban League, Indian Health Board). Finally, we will utilize recruitment resources from the UMN and 
UPITT Clinical Research and Translational Science Institutes (CTSI): CTSI PITT+ME (UPITT) research 

 
 
PACBACK Protocol V8 page 31 
      
patient registry, i2b2 Cohort Discovery tool and StudyFinder (UMN), and ResearchMatch (National 
Registry). 
 
4.3.2 Documentation of reasons for ineligibility and for non-participation of eligible candidates 
A comprehensive list of all candidates who were screened, whether or not they were enrolled, and the 
reasons for ineligibility or non-participation (if applicable) will be maintained electronically. A summary 
of the number of candidates screened and enrolled with reasons for ineligibility or non-participation will 
be monitored by the CCC and DCC at routine operational meetings.  
 
4.3.3 Consent procedures 
A full description of the consent process is described in section 6, Study Procedures. All participants will 
provide written consent prior to enrollment.  
 
4.3.4 Baseline screening procedures 
Screening consists of a preliminary web-based survey, followed by a phone screen with study staff and an 
in-person visit to confirm eligibility.  
 
4.3.5 Randomization procedures 
We will use block randomization within site using variable blocks of size 12 or 16 participants (since 4 
study groups). Using block randomization ensures that equal numbers are randomized to the control and 
intervention arms, and that the intervention groups are balanced at periodic enrollment intervals. 
Randomization will be stratified on site and on baseline STarT Back screening tool risk status (medium 
risk, or high risk of cLBP).58 104 The study web portal will be available 24 hours a day, 365 days a year, 
for screening and randomization. In the event of planned or unplanned portal downtime, a telephone-
based backup protocol will be administered by the DCC. From January 2021 to October 2021, patients 
were randomized to remote-delivery of (1) SSM or (2) MC due to the COVID-19 pandemic.  
5. STUDY INTERVENTIONS  
Patients will be randomized to one of the following treatment groups within the 2x2 factorial design: (1) 
SMT, (2) SSM, (3) the combination of SMT+SSM, or (4) MC. The initial treatment period is 8 weeks. 
Decisions regarding visit frequency will be made collaboratively by the provider and patient, as is typical 
in real-world settings. Participants will be required to attend 75% of prescribed intervention visits to be 
considered compliant over the 8-week period. In addition, participants have the option to receive 
additional treatment in the group to which they were randomized if they experience a recurrence of an 
acute LBP episode during the 10 month follow-up period. This additional treatment will occur in the same 
study clinic, or virtually using HIPAA compliant Zoom, with the same provider when possible. 
Participants will not be offered the option to receive treatment delivered in any of the other 3 study 
groups.  
 
The primary goal of SMT is to address the biological and physical aspects of LBP (e.g., spinal 
dysfunction) with the intention of restoring maximum movement and functional ability of the spine. The 
goals of SSM are to primarily address the psychosocial aspects of acute and sub-acute LBP, by providing 
patients’ the opportunities to develop their capacity and motivation to self-manage their LBP in an 
adaptive manner.45 108 The goals of the MC group will be to provide care for acute and subacute LBP as it 
would typically be delivered in primary care settings. 
5.1 
Interventions, Administration, and Duration  
5.1.1 Spinal manipulation therapy (SMT) 

 
 
PACBACK Protocol V8 page 32 
      
The SMT techniques are based on those used in the UK BEAM Trial122 and agreed upon by PT, DC, and 
osteopathic professional groups. SMT will be provided by licensed physical therapists (PT-MPT's and 
DPTs) and licensed doctors of chiropractic (DCs) at the UMN and UPitt who have a minimum of 3 years 
clinical experience. Decisions regarding visit frequency will be made collaboratively by the provider and 
patient, as is typical in real-world settings. SMT will be provided within research and outpatient clinics 
affiliated with the UPITT and UMN. Dedicated clinics in Pittsburgh (Physical Therapy Clinical and 
Translational Research Center (PT-CTRC) and Homewood Community Engagement Center Wellness 
Pavilion and Minnesota (The Berman Center for Outcomes and Clinical Research and Hennepin County 
Medical Center Integrative Care Clinic) will function as the main clinics for the trial. In case of a 
recurrence of an acute LBP episode during the 10 month follow-up period participants have the option to 
continue to receive spinal manipulation therapy; this treatment will occur in the study clinics with the 
same provider if possible. They will not be offered the option to receive treatment delivered in any of the 
other 3 study groups. 
 
SMT is considered safe for the treatment of LBP, but side effects associated with SMT are common and 
benign. Approximately 50% of patients report one reaction, most commonly local discomfort which 
resolves within a day.7 99-102 Serious adverse events (SAEs) following lumbar SMT are rare7 and are 
estimated to occur once per million to several million visits and include cauda equina syndrome, disc 
herniation, fracture, hematomas or hemorrhagic cysts.123 
 
5.1.2 Supported self-management (SSM) 
The goals of SSM are to primarily address the psychosocial aspects of acute and sub-acute LBP, by 
providing patients’ the opportunities to develop their capacity and motivation to self-manage their LBP in 
an adaptive manner.108 124 The program is theory informed and evidence based. It is adapted from previous 
SSM programs delivered by PTs, DCs, and other professionals for musculoskeletal and LBP conditions.11 
106-108 124 SSM will be provided by licensed physical therapists (PT-MPT's and DPTs) and licensed doctors 
of chiropractic (DCs) at the UMN and UPitt who have a minimum of 3 years clinical experience. PTs and 
DCs will be trained to deliver the SSM program; it includes the following components:  
● Psychological/behavioral strategies (e.g., pleasant activity planning, pacing, cognitive 
restructuring, problem solving). 
● Mind-body approaches (e.g., muscle relaxation, breath awareness, focused attention, guided 
imagery, simple symptom management, postural awareness and strengthening LBP exercises). 
● Lifestyle advice (e.g., sleep, daily activities, prevention of social isolation). 
● Pain education (e.g., pain theories, prognosis, and evidence based pain management tips).105 
 
One-on-one sessions, will be provided by licensed PTs and DCs via HIPAA compliant video conference 
(e.g., Zoom) or at dedicated clinics in Pittsburgh (Physical Therapy Clinical and Translational Research 
Center (PT-CTRC) and Homewood Community Engagement Center Wellness Pavilion and Minnesota 
(The Berman Center for Outcomes and Clinical Research and Hennepin County Medical Center 
Integrative Care Clinic). Session frequency will be decided collaboratively by the provider and patient 
depending on the patient’s needs and abilities. 107 Informational and instructional materials including, 
audio recordings and  a workbook (intended for use by patients on their own at their preferred pace) will 
be provided.108 
 
At the first visit, the PT/DC will provide an overview of the SSM program, and together the clinician and 
patient will assess which psychological, lifestyle and behavioral strategies would benefit the patient. This 
will be done using a quick, interactive assessment that serves to educate, motivate and develop the 
patient-practitioner bond. The assessment will address common impacts of pain including mood, social 
connections, relationships, thoughts about LBP and their current situation, activities, sleep and stress. The 
PT/DC will also perform a simple and repeated movement assessment (flexion/extension, side gliding) to 
determine if directional preferences exercises (as a form of symptom self-management) would be helpful. 

 
 
PACBACK Protocol V8 page 33 
      
If needed, postural awareness exercises (neutral spine, abdominal curl ups, side planks, and quadruped) 
will be prescribed to support neutral spine posture, and will include breath awareness to facilitate the 
mind-body connection. Strengthening exercises to support daily living (bridging, squats and lunges, all 
done with ‘spine sparing’ postures) will also be prescribed if necessary. 
 
In case of a recurrence of an acute LBP episode during the 10 month follow-up period, participants have 
the option to continue to receive the supported self-management treatment; this treatment will occur in the 
study clinics with the same provider if possible. They will not be offered the option to receive treatment 
delivered in any of the other 3 study groups. 
 
Side-Effects: Risks associated with the supported self-management group are considered extremely rare. 
No SAEs were reported in trials including physical and biopsychosocial treatment components.7 
Participants may experience emotional discomfort as a result of discussing the impacts of their pain (e.g., 
mood, social connections, etc.). Participants may also experience physical discomfort as a result of the 
directional preference, postural awareness, and strengthening exercises. All of these side effects are 
expected to be temporary and short-lasting.  
 
5.1.3 Combined SMT and SSM 
The goals of the combined SMT+SSM group are to address the biological/physical and psychosocial 
components of LBP in an accessible and integrated manner. Delivery of SMT and SSM will be by the 
same provider (licensed PTs or DCs) over an 8-week period using the protocols described above. In case 
of a recurrence of an acute LBP episode during the 10 month follow-up period participants have the 
option to continue to receive this combined treatment; this treatment will occur in the study clinics 
(Physical Therapy Clinical and Translational Research Center (PT-CTRC) and Homewood Community 
Engagement Center Wellness Pavilion and Minnesota (The Berman Center for Outcomes and Clinical 
Research and Hennepin County Medical Center Integrative Care Clinic), or virtually using HIPAA 
compliant Zoom, with the same provider if possible. Trial participants will not be offered the option to 
receive treatment delivered in any of the other 3 study groups. Descriptions of these interventions are 
described above.  
 
5.1.4 Medical care 
Medical care is informed by the American College of Physicians guidelines on noninvasive treatment for 
LBP46 and reflect what is delivered in primary care clinics. Medical care will be provided by licensed 
medical providers (e.g., MD, APN, PA) with a minimum of 3 years managing musculoskeletal pain 
patients. Decisions regarding medical care (e.g., pharmacological management) and visit frequency 
during the initial 8-week intervention period will be made collaboratively by the provider and patient, as 
normally occurs in clinical practice. Care will be provided via HIPAA compliant video conference (e.g., 
Zoom), within outpatient clinics affiliated with UPITT and UMN, and/or over the phone: the Physical 
Therapy Clinical and Translational Research Center, Homewood Community Engagement Center 
Wellness Pavilion and the Berman Center for Outcomes and Clinical Research , respectively. In case of a 
recurrence of an acute LBP episode during the 10 month follow-up period participants have the option to 
continue to receive medical care; this treatment will occur in the study clinics with the same provider if 
possible. They will not be offered the option to receive treatment delivered in any of the other 3 study 
groups during this follow-up period. 
 
Medication Delivery: Medication will be prescribed topically and/or orally, in tablet form. Participants 
can purchase over-the-counter (OTC) medications (e.g., Ibuprofen, 4% lidocaine patches); however, these 
will be paid for by the study. Prescription medications (see Required and Allowed Interventions) will be 
sent to the patient’s preferred pharmacy by the provider or research staff. 
 

 
 
PACBACK Protocol V8 page 34 
      
● The first visit will occur in the clinic or via virtual HIPAA compliant videoconference (Zoom). 
Clinicians will review information collected during the screening phase, and conduct their own 
medical history and exam as needed. A treatment plan will be established, and the provider will 
follow-up with the participant (in-person, via videoconference or by phone) within 7 business 
days of the initial visit.  
 
● The second and subsequent encounters between the provider and participant may occur in the 
clinic, virtually using HIPAA compliant Zoom, or over the phone. During this encounter the 
provider will get a sense of how the patient is responding to the treatment. Medication 
adjustments, including class, dose, and frequency can be made based on the participant's current 
presentation and response. As described above, the need for subsequent in-person, 
videoconference visits, and/or phone calls will be made collaboratively between the provider and 
participant.  
 
Side-Effects 125: Pharmacological therapies are associated with increased AEs compared to placebo.7 
Several protections are in place to minimize risks, including reminding participants to take their 
medication as prescribed and to contact the study clinician if there are changes to their medication 
regimens to avoid drug-drug adverse interactions. Also, clinicians will assess the potential for risk factors 
based on the patient’s medical history prior to prescribing/recommending (prescription and OTC) 
medications and will suggest the lowest effective dose(s) for the shortest time necessary.  
 
● Allergic reaction 
● Cardiovascular symptoms: hypotension, edema, flushing,  
● Central nervous system: dizziness, weakness, ataxia, fatigue, drowsiness, headache, stimulation, 
insomnia, sedation, tremor, syncope 
● Chemical dependence 
● Dermatologic: itchy skin, rash, sweating 
● Endocrine & Metabolic: weight gain 
● Gastrointestinal symptoms: nausea, vomiting, dry mouth, abdominal pain, dyspepsia, diarrhea, 
GERD, constipation, bleeding 
● Kidney failure (excessive NSAIDs use) 
● Liver failure (excessive Acetaminophen use) 
● Ophthalmic: visual field loss, blurred vision  
● Respiratory: depression, arrest, apnea 
 
5.2 
Handling of Study Interventions  
5.2.1 Spinal manipulation therapy  
Required Interventions 
Overall, the SMT protocol is largely pragmatic as it includes core manipulative practices with sufficient 
flexibility to be representative of the professions most commonly delivering SMT.122  
● SMT will be applied to the spine (below the fifth thoracic vertebrae), and sacroiliac joints. 
● SMT will consist of mobilization (low velocity, low-high amplitude passive movements) and/or 
manipulation (high velocity, low amplitude thrust) at the clinician’s discretion.  
● SMT may be applied unilaterally or bilaterally at one or more locations. 
 
Allowed Interventions 
● Soft tissue techniques which include cross-fiber stretch, longitudinal stretch, direct pressure, and 
deep friction applied to soft tissue from the lower ribs to the gluteal folds.  
● Lumbar neural mobilization 

 
 
PACBACK Protocol V8 page 35 
      
● Clinicians may use heating pads for up to 10 minutes to facilitate the delivery of SMT.  
 
Prohibited Interventions 
Clinicians applying SMT are prohibited from providing the following: 
● SMT to the neck or upper thoracic spine (above the sixth thoracic vertebrae) 
● SMT directed at extremity joints (e.g., hip joint) 
● Instrument assisted SMT (e.g., activator)  
● Applying passive modalities other than heat (e.g., TENS & ice) 
● Lumbar belts, strapping, taping etc. 
● Recommending bed rest 
● Exercise recommendations beyond those described in section 5.3 
● Educational materials or recommendations for self-care/self-management beyond those described 
in section 5.3 
● Recommendations to use Mind-body practices (e.g., yoga, Tai Chi, meditation) or  intervention 
elements described in the SSM protocol 
● Assessment of need for symptom management exercises (flexion/extension, side gliding, postural 
awareness exercises, and strengthening exercises)  
 
 
Training 
Clinicians providing SMT will be required to attend at least 2, 2-hour training sessions prior to delivering 
study interventions. Refresher training sessions during the treatment phase will be conducted annually 
thereafter. Training sessions will be led by study investigators and will cover the goals of the SMT 
intervention, including hands-on demonstration and practice, and required, allowed, prohibited 
interventions as outlined in the protocol, and the importance of maintaining equipoise to avoid 
contamination between the SMT and SSM groups. It will include a combination of in-person (e.g., 
videoconference) and interactive workshops, webinars and online training formats. Monthly video and/or 
audio conferences will be held to build a community of practice to problem-solve and facilitate a degree 
of consistency between providers and across sites.  
 
5.2.2 Supported self-management 
Required Interventions 
The following are considered standard elements of the SSM intervention:  
● Presenting rationale for biopsychosocial approach to pain management and performing 
assessment of need for other psychological/social/behavioral strategies (see options below) 
● Pain theories 
● Favorable prognosis 
● Evidence- based pain management tips 
● Relaxed breathing, progressive muscle relaxation, mental imagery  
● Encourage activities of daily living 
● Encourage regular physical activity 
● Postural awareness (neutral spine) 
● Acknowledging/problem- solving challenges of integrating SSM strategies into life 
● Encouragement/reassurance 
 
Allowed Interventions 
The following summarizes optional SSM elements (based on patient needs): 
● Cognitive restructuring (shifting thoughts and attitudes to reduce balance out catastrophizing) 
● Problem- solving as needed (around pain impacts to maximize well being) 
● Pleasant activity planning (helpful for those who have depressive symptoms) 

 
 
PACBACK Protocol V8 page 36 
      
● Pacing (having an awareness of up/down time needed, plan activities to manage with pain) 
● Symptom management exercises (flexion/extension, side-gliding) 
● Postural stabilization exercises (abdominal curl-ups, side planks, and quadruped) 
● Strengthening exercises to support activities of daily living (bridging, squats and lunges, all done 
with ‘spine sparing’ postures) 
 
Prohibited Intervention 
SMT providers delivering the SSM intervention are prohibited from delivering: 
● SMT as described in section 5.2.1 
● Applying passive modalities (e.g., TENS, heat, ice) 
● Exercise recommendations, including rehabilitative exercises that fall outside of what is described 
in the SSM allowable interventions 
● Educational materials and recommendations for self-care beyond those described in section 5.3 
and what is described in the SSM allowable interventions 
● Recommendations to use mind-body practices not described in required or allowable SSM 
interventions 
● Lumbar belts, strapping, taping, etc. 
● Recommending bed rest 
 
Training 
The goal of SSM training is to facilitate providers’ confidence and ability to act as an effective coach for 
patients’ in their self-management. Clinicians providing SSM will be required to complete online training 
materials covering information in the key SSM content areas. In addition, they will be required to attend 
face-to-face training sessions (e.g., via Zoom) led by Drs. Greco, Evans, and other investigators. Face-to-
face training sessions will be highly interactive, and focus on the application of assessment and 
intervention elements of SSM, including delivering SSM in the remote environment. Prohibited 
interventions and other study specific related procedures (e.g., intervention documentation) will also be 
addressed. Monthly video and/or audio conferences will be held to build a community of practice and to 
problem-solve and facilitate a degree of consistency between providers and across sites. Refresher 
training sessions during the treatment phase will be conducted annually thereafter.  
 
5.2.3 Medical care 
Required Interventions 
Participants are required to meet with their medical provider to discuss treatment options. 
 
Allowed Interventions 
The evidence-informed medical care intervention is largely pragmatic as it includes different OTC and 
prescription drug classes and doses, reflective of what is available in clinical practice.  
● The clinician and patient should select OTC or prescription nonsteroidal anti-inflammatory drugs 
(NSAIDs) or skeletal muscle relaxants (SMRs)46 as first-line treatment in this study.  
● The choice between NSAIDs and SMRs should be individualized on the basis of patient 
preferences and likely individual medication risk profiles.  
● In addition, providers may recommend the use of heat, massage, or acupuncture; however, no 
formal referrals will be made. 
 
Additional recommendations for commonly used OTC and prescription drug options that are not 
supported by good data are permissible for participants who are unresponsive to or unable to tolerate first-
line medications:  
● Acetaminophen 
● Lidocaine patches 

 
 
PACBACK Protocol V8 page 37 
      
● NSAID creams 
● Opioids 
● Benzodiazepines  
● Antiseizure medications 
● Tricyclic antidepressants 
● Selective Serotonin Reuptake Inhibitors and/or Serotonin Norepinephrine reuptake inhibitors  
 
Prohibited Interventions/Recommendations 
Medical providers are prohibited from recommending the following interventions: 
● Medication(s) different from what is described in allowed interventions above.  
● Referral for physical therapy, manual treatment, cognitive behavioral therapy, or any treatments 
provided by a PT, DC, or psychologist.  
● Referral for interventional procedures (e.g., epidural steroid injections, intramuscular and facet 
joint injections) 
● Exercise recommendations beyond those described in section 5.3 
● Educational materials or recommendations for self-care beyond those described in section 5.3 
● Recommendations to use Mind-body practices (e.g., yoga, Tai Chi, meditation) or intervention 
elements described in the SSM protocol 
● Lumbar belts, strapping, taping etc. 
● Recommending bed rest 
 
Training 
Clinicians providing medical care are required to attend at least 2, 2-hour training sessions prior to 
delivering study interventions. Training will focus on the medical care protocol (e.g., what is required, 
allowed, prohibited, safety assessments, and AEs), the operating procedures at each respective clinic, and 
delivering MC via videoconference when applicable. Refresher training sessions during the treatment 
phase will be conducted annually thereafter. Training sessions will be led by study investigators and cover 
required, allowed, and prohibited interventions as outlined in the protocol. Monthly video and/or audio 
conferences will be held to build a community of practice to problem-solve and facilitate a degree of 
consistency between providers and across sites.  
 
5.3 
Concomitant Interventions 
Required Interventions 
All participants will receive basic standardized information regarding the generally favorable prognosis of 
acute and sub-acute LBP. We will provide patients with an updated version of the Back in Action book 11 
44 in print and/or electronic formats. The Back in Action book: 
● Encourages patients to engage in their normal activities as soon as possible, even if it causes 
some pain.  
● Encourages general aerobic exercise like walking, swimming, bicycling. 
● Provides a very brief summary of the general causes of LBP, reassurance that it is rarely due to a 
serious problem, and that the majority of cases do not require specialty care or imaging.  
● Emphasizes the patient’s role in facilitating their own recovery by providing some general 
recommendations for symptom management (e.g., use of heat, changing positions frequently).  
 
Allowed Interventions 
Participants will be allowed to use OTC medications as needed during the course of the study. In addition, 
participants will be allowed to continue self-care practices (e.g., heat, stretching) for LBP they used prior 
to the study. Participants not assigned to MC who experience a significant worsening of LBP symptoms 
that cannot be managed by the assigned and concomitant interventions will be referred to the study’s 

 
 
PACBACK Protocol V8 page 38 
      
medical care provider for a short-course of ‘rescue medications’, using a protocol successfully 
implemented, but rarely required, in previous studies by the investigators.10 11 See section 5.5. 
 
Treating clinicians, in consultation with the PIs, may refer in the case of AEs or if LBP complications 
develop that cannot be adequately managed with the assigned intervention (e.g., disc herniation with 
progressive neurological deficits). Participants will be informed to seek any required care for all 
conditions unrelated to the study. 
 
Prohibited Interventions 
Participants will be asked to limit treatment to their assigned intervention for the length of the initial 8-
week intervention period; similarly providers will be taught to refrain from delivering interventions that 
fall outside the scope of the study protocols (see above). However, participants retain the right to 
discontinue care at any time. 
5.4 
Adherence Assessment  
The total number of treatments will be decided by the treating clinician based on each individual 
participant’s clinical presentation and response to care, as is done in clinical practice. We anticipate 4-6 
visits being prescribed for most participants receiving SMT, 4-8 visits for most participants receiving 
SSM, and 2-4 visits for most participants receiving medical care. Participant adherence to assigned 
interventions will be documented at each visit in the clinical notes. 
 
Treatment adherence has been defined in the Threshold Criteria for Transition as attending ≥75% of 
prescribed intervention visits. We have expanded on this definition by including a minimum number of 
visits for each intervention and requiring participants not drop out of active care to be considered 
adherent. A minimum of 2 sessions will be required for participants in SMT and MC, and minimum of 4 
for the two groups receiving SSM, but additional sessions may be needed.  
  
Intervention fidelity will be assessed by review of treatment visit activities that address required, allowed 
and prohibited interventions. In addition, fidelity will be assessed by video/audio recordings or in person 
observations of randomly determined intervention visits.  Fidelity assessments will occur monthly, for six 
months, on each provider currently treating patients, then quarterly thereafter. If concerns arise during 
quarterly reviews, the provider may resort back to monthly fidelity checks as needed. The DCC will 
monitor the treatment administered forms for activities defined as ‘out of scope’ for the defined 
intervention (e.g., spinal manipulation delivered to a participant assigned to structured self-management). 
Out of scope activities indicating potential crossover will be flagged through automated real-time alerts 
created by the DCC which will immediately be sent to the relevant site’s PI and study coordinators. The 
site study coordinators are best suited for contacting providers, as they will be familiar to them and will 
have developed collaborative working relationships that ensure successful project implementation. 
Additional actions would include remedial training for the providers and potential removal from 
providing study care. 
 
 
5.5 Rescue Medication 
Participants not assigned to MC who experience a significant worsening of LBP symptoms that cannot be 
managed by the assigned and concomitant interventions will be referred to a study medical care provider 
for a short-course of rescue medications. Skeletal muscle relaxants and non-steroidal anti-inflammatories 
are the first line rescue medications that will be offered based on the participant's individual medication 
risk profile. Additional medication may be used when first line rescue medications are contraindicated or 
do not sufficiently manage the participant’s pain (e.g., opioids, benzodiazepines, antiseizure 
medications).46 Use of rescue medication will be monitored and differences across intervention arms will 

 
 
PACBACK Protocol V8 page 39 
      
be compared.  Further, medical providers should make reference to the Back in Action booklet and 
reinforce its content (e.g., the favorable prognosis for acute/subacute back pain and the importance of 
staying active). 
6. STUDY PROCEDURES 
6.1  
Schedule of Evaluations  
 
See Table on next page

 
 
PACBACK Protocol V8 page 40 
      
 
Assessment 
 
Initial 
Screen 
 
Baseline/ 
Enrollment 
(Day 0) 
 
Intervention 
Visits 
(Months 0-2) 
 
Weekly 
Follow-Up 
(Weeks 1-52) 
 
Follow-Up 
(Week 2) 
 
Monthly 
Follow-Up 
(Months 1-
12) 
 
Follow-Up 
 
(Month 1) 
 
Follow-Up 
 
(Month 2) 
 
Follow-Up 
 
(Month 6) 
 
Follow-Up 
 
(Month 12) 
Informed Consent 
x 
x 
 
 
 
 
 
 
 
 
Demographics 
x 
x 
 
 
 
 
 
 
 
 
Medical History & Current Medications 
 
x 
 
 
 
 
 
 
 
 
Physical Exam including objective 
outcomes 
 
x 
 
 
 
 
 
x 
 
 
Inclusion/Exclusion 
x 
x 
 
 
 
 
 
 
 
 
Technology Assessment** 
 
 
x 
 
 
 
 
 
 
 
 
COVID -19 Impact  
 
x 
 
 
 
 
 
x 
x 
x 
TUQ** 
 
x 
 
 
 
 
x 
x 
 
 
STarT Back Screening Tool Status 
x 
 
 
 
 
 
 
x 
x 
x 
Chronic LBP status (NIH RTF definition) 
x 
x 
 
 
 
 
 
 
x 
x 
Chronic interference with daily activities  
x 
x 
 
 
 
 
 
 
x 
x 
LBP intensity  
x 
x 
 
x 
 
 
 
 
 
 
LBP frequency 
 
x 
 
x 
 
 
 
 
 
 
Pain Trajectory 
 
x 
 
 
 
 
 
 
 
x 
Implementation Measures 
x 
x 
 
 
 
 
 
x 
x 
x 
Randomization/Enrollment 
 
x 
 
 
 
 
 
 
 
 
Treatment Administered (booster sessions 
allowable in months 3-12) 
 
 
x 
 
 
 
 
 
 
 

 
 
PACBACK Protocol V8 page 41 
      
Intervention Uptake  
 
 
 
 
 
 
x 
x 
x 
x 
Disability, PROMIS, healthcare and 
medication use, and productivity loss  
 
x 
 
 
 
x 
 
 
 
 
Adverse events* 
 
x 
x 
 
 
x 
 
 
 
 
Satisfaction and global improvement 
 
 
 
 
 
 
 
x 
x 
x 
Non-specific factors (HEAL) 
 
x 
 
 
x 
 
x 
x 
x 
 x 
Psychosocial Mediators  
(self-efficacy, coping, kinesiophobia, and 
pain catastrophizing) 
 
x 
 
 
 
 
 
x 
x 
x 
Participant Close Out 
 
 
 
 
 
 
 
 
 
x 
*Participants can also report adverse events to the PI’s or study staff at any point during the trial 
** Technology Assessment and the Telehealth Usability Questionnaire (TUQ) will be administered to participants who are enrolled in the 2-arm study only. Technology Assessment and the 
Telehealth Usability Questionnaire (TUQ) may be administered to participants in the 4-arm study if applicable (e.g., if screening and/or treatments are done virtually). 

 
 
PACBACK Protocol V8 page 42 
      
 
6.2 
Description of Evaluations  
6.2.1 
Screening Evaluation 
The following evaluations will occur to determine if the candidate is eligible for the study.  
 
Consenting Procedure 
● 
Potential participants will consent at 3 different time points: the initial screen online, phone 
screen, and at an in-person or videoconference baseline screening appointment.  
Initial screening 
● Potential participants will read a brief online description of the study, including the purpose, 
study design and procedures to help them decide if they want to complete the initial screen. 
Consent is provided by checking a box that will allow them to proceed with the initial screening.  
● Phone Screening  
 
Baseline Screening Appointment 
● 
Potential participants will be given a copy of the consent form to review on their own that will 
describe the screening and study procedures. See Section 11.2 for a full description of the consent 
form. They will be given ample time to review the form on their own and ask questions. 
● 
The Principal Investigators, or designee (i.e., research staff) will review the consent form, section 
by section, one-on-one with each potential participant; participants will be invited to ask 
questions as they proceed through each section.  
● 
Informational materials (e.g., flow chart or PowerPoint) will be used to facilitate understanding.  
● 
All participants will be given information related to the COVID-19 pandemic and potential risks 
associated with research participation 
● 
A signed and dated consent form will be obtained from each study candidate and research staff 
conducting the consent process will sign as a witness. All participants will be given a copy of the 
signed consent form for their personal records. Participants will provide electronic consent (e-
Consent in REDCap) or written consent. 
● 
Original signed consent forms will be secured in the respective participants' research file at each 
of the respective clinical coordinating centers or in REDCap. Scanned consent forms will be sent 
electronically to the DCC for monitoring. 
● 
Only individuals who demonstrate comprehension will be considered eligible to participate. 
Persons who are not able to read and write in English or consent for themselves are ineligible.  
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. See Section 11.2 for 

 
 
PACBACK Protocol V8 page 43 
      
additional information about the consent form. In addition, staff will complete human subjects training in 
accordance with the IRB of record and/or the staff member’s institutional human subject training 
requirements.   
 
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 a potential 
participant. See the Participants and Confidentiality section for additional information.    
 
If potential 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 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 or mailed 
to the participant's home.  
 
Screening 
Screening will occur at 2 time points: an initial screen (online and phone) and a face to face (e.g., in-
person or videoconference) baseline screening appointment.  
 
Initial Screening (Online/Phone) 
● 
Following consent, potential participants will be asked a series of self-report questions to screen 
basic eligibility. Persons who meet basic inclusion criteria (e.g., age, medium or high risk on 
STarT Back Screening Tool, LBP intensity of 3 or higher, English literacy) and who otherwise 
have no obvious exclusions (e.g., pregnancy, history of surgical fusion of lumbar spine) will be 
contacted by study staff, who will ask specific health-related, questions pertaining to inclusion 
(e.g., LBP episode duration).  
● 
In-person or videoconference screening appointments will occur as soon as possible, but must 
occur within 30 days of completing the phone screen; otherwise, the initial phone screen will be 
redone. 
Baseline Screening (In Person/Videoconference) 
● 
Written or e-informed consent will be collected from participants prior to any screening 
procedures at this visit.  
● 
Participants will complete self-report questionnaires to determine eligibility that include: 
o 
Demographics 
o 
Current back pain intensity and duration       
o 
Diagnosis of serious mental health disorders and related treatment; if major depression is 
suspected or reported by the participant, the Patient Questionnaire-2 (PHQ-2)126 will be 
administered; a score of greater than or equal to 3 will lead to additional screening for 
suicidality. Suicidal ideation will be collected using question 12 from the Quick 

 
 
PACBACK Protocol V8 page 44 
      
Inventory of Depressive Symptomatology-Self Report (QIDS-SR)127 and a score of 
greater than or equal to 2 warrants exclusion and referral.    
o 
Substance abuse. All participants who indicate they drink alcohol will be asked if they 
drank more alcohol than intended in the previous 6 months. If affirmative, additional 
questions will be asked related to how often they have drunk 6 or more drinks on one 
occasion. Those who indicate having done so at least weekly will receive additional 
screening: the 10-item Alcohol Use Disorders Identification Test (AUDIT) for alcohol.128 
Scores of greater than or equal to 20 on the AUDIT is exclusionary and warrants 
referral. AUDIT will be available to administer at any time if the clinician suspects a 
problem. Participants reporting the use of illegal drugs or prescription medication for 
nonmedical reasons in the last year will complete the 10-item Drug Abuse Screening Test 
(DAST)129-131 for drugs. Scores of greater than or equal to 6 on the DAST is exclusionary 
and warrants referral. The DAST will be available to administer at any time if the 
clinician suspects a problem. 
o 
Comorbidities 
● 
A licensed healthcare provider (e.g., DC, PT, MD, advanced practice provider) will conduct a 
medical history and a focused low back physical exam that will include posture assessment, 
orthopaedic and neurological tests, palpation (in-person only) etc. Current medications and vitals 
(in-person only) will be collected. Participants undergoing screening assessment via 
videoconference will be asked additional screening questions regarding potential hypertension as 
remote assessment of blood pressure is not planned. Suspicion of declining cognitive function 
during clinical exam will lead to administration of the Mini-mental state examination. A score of 
23 or below is exclusionary.132 
● 
Women of childbearing age require a pregnancy test. Women who have had a hysterectomy or 
are postmenopausal will not require a pregnancy test. Persons who are in same sex relationships, 
transgender and/or transitioning, celibate, LBTGQ+, can refuse a pregnancy test and still be 
eligible to participate. For remote videoconference baseline appointments, participants will be 
mailed a pregnancy test and instructed to take the test during the baseline appointment and show 
research staff the result. 
● 
Potential participants who present with signs and symptoms suggestive of a specific cause of LBP 
(e.g., nephrolithiasis, infection, fracture), contraindication to SMT or SSM (e.g., inflammatory 
arthropathies of the lower back), or other condition that warrants medical attention will be 
referred to their medical provider for follow-up and management.  
 
6.2.2 
Enrollment, Baseline, and/or Randomization 
Enrollment 
Enrollment is defined as the date of randomization at which point all eligibility criteria are confirmed and 
the individual has agreed to participate; this is recorded on a case-report form. AEs will be collected after 
the participant is enrolled. Participants will be told to contact study staff and/or providers about any health 
related changes they experience. See Safety Assessments and the DSMP for additional details.  

 
 
PACBACK Protocol V8 page 45 
      
 
Baseline Assessments 
For participants who have successfully been screened for eligibility and are enrolled into the study, 
baseline assessments are performed against which to measure the study outcome. These will also ensure 
the groups are balanced with respect to baseline characteristics.  
 
Primary and secondary outcomes will be measured using web-based, self-report questionnaires 
administered free of provider and investigator influence. 
 
Baseline characteristics  
Important baseline characteristics (e.g., demographics, past healthcare use, COVID-19 impact190, LBP 
duration, prior episodes of LBP, visual trajectory questionnaire for pain186, Quebec Task Force 
classification of spinal disorders133) will be collected through web-based, self-report questionnaires and 
the screening provider’s medical history and physical exam. Baseline measures included in the NIH 
research task force’s minimum dataset will be collected.73 
 
Primary Outcome Measures 
The following primary outcome measures will be collected during the baseline assessment.  
 
● 
Low back pain impact is defined as a combination of pain intensity, pain interference with normal 
activities, and functional status, using 9 items of the 29-item PROMIS short form. These items 
have substantial research support to validate their discriminatory and prognostic importance. 
Scores on the 9 PROMIS-based items yielding Impact Stratification range from 8 (least impact) 
to 50 (greatest impact).191 
● 
LBP Intensity: participants will be asked to rate their average LBP over the last week on an 
ordinal 11-box NRS (0=no LBP, 10=the worst LBP possible). Several studies have shown that 
ordinal pain scale measures perform as well as the 10-cm Visual Analog Scale (VAS),134 a 
simple, frequently used valid assessment of variation in pain intensity119 135 and a reliable measure 
of treatment efficacy.136 The advantage of the 11-box scale over the VAS is that it is easier to 
administer and score.119 
● 
Low back disability will be measured with the modified Roland Morris Disability Questionnaire, 
a 24-item questionnaire that measures the degree to which the low back problem or leg pain 
restricts patients’ daily activities. It has a high level of internal consistency, construct validity, 
and responsiveness.120  
 
Secondary Outcome Measures  
● 
The PROMIS-29 Profile v2.0 Instrument (www.nihpromis.org) as recommended by the NIH RTF 
will be used with the exception of the question on pain intensity which is collected elsewhere on a 
weekly basis.73 This includes the following measures: pain interference with normal activities, 
physical function, anxiety, depression, fatigue, sleep disturbance and the ability to participate in 
social roles and activities.  

 
 
PACBACK Protocol V8 page 46 
      
● 
LBP frequency will be collected by asking participants to report the number of days LBP has 
been a problem in the past 7 days.73 
● 
OTC and prescription medication use for LBP, including class and frequency by class. 
● 
Health care utilization including provider visits, ER visits, MRIs, injections, hospitalizations, and 
surgeries. 
● 
Productivity loss related to LBP (e.g., missed work, reduced productivity while at work) will be 
assessed using questions from the Institute for Medical Technology Assessment’s productivity 
cost questionnaire.137 
● 
Physical exam objective outcome measures including QTF classification133, timed up and go test, 
5 times sit-to-stand test 185, 187, 188 , and the sock test.185  
● Chronic interference with daily activities assessed using “how often has low-back pain interfered 
with your ability to do regular activities over the past 6 months?” on a 3-item scale (less than half 
the days in the past 6 months, at least half the days in the past 6 months, every day or nearly 
every day in the past 6 months). 
 
● Prevention of cLBP at 6 and 12 months, as measured by the proportion of patients in each 
group meeting the definition by the NIH Task Force on Research Standards for Chronic LBP 
(i.e., ongoing low back problem on ≥50% of days over past 6 months). 
 
 
Psychosocial Mediator Measures 
● 
Self- efficacy will be assessed using the 22-item Chronic Pain Self-Efficacy Scale that will be 
adapted for acute/sub-acute pain.138 
● 
Coping will be assessed using an adapted version of the 28-item Brief COPE instrument.139  
● 
Kinesiophobia will be measured using the 11-item Tampa Scale for Kinesiophobia demonstrated 
to have internal consistency, responsiveness and validity similar to the original 17-item 
instrument.140 
● 
Catastrophizing (Pain Catastrophizing Scale141) is measured using the 13-item Pain 
Catastrophizing Scale; it uses a 5-item point scale (0=not at all, 4 all the time) and has internal 
consistency and validity. 
● 
Measurement of key non-specific factors that may influence outcomes will be measured using the 
short forms for positive outlook (6-item) from the Healing Encounters and Attitudes Lists 
(HEAL) 
Randomization 
Randomization will precede intervention administration. Randomization will occur within 7 business 
days of finalizing eligibility determination.  Persons who are not randomized within this time frame will 
repeat the in-person/videoconference screening. Interventions will be initiated within 7 business days of 
randomization/ enrollment.  

 
 
PACBACK Protocol V8 page 47 
      
 
6.2.3 
Blinding 
Blinded Personnel:  
Blinding of treatment providers and participants is not feasible. However, the following steps will be 
taken to minimize potential bias and enhance study rigor:  
 
a). all study personnel involved in screening and enrollment will be masked to upcoming randomization 
assignments;  
b). all study personnel involved in outcome assessment will be independent of intervention delivery, and 
trained in ensuring unbiased data collection and blinded to study assignment until database is locked;  
c). only a single member from the DCC will be unblinded and have access to treatment group assignment 
for the purpose of creating closed DSMB reports; and  
d). participants will be queried in self-report questionnaires as to whether or not anybody attempted to 
influence their responses. 
 
6.2.4 
Follow-up Visits 
Intervention Visits  
The following information will be collected at each intervention visit, which will occur as needed 
throughout the one year as there is no set schedule of treatments: 
o 
Treatment delivery format – in-person, videoconference or phone 
o 
Treatment administered – provider’s record treatment administered including required, 
allowed and prohibited treatments to assess treatment fidelity and adherence. (Clinical 
notes will be documented in the medical record as required for patient management and 
for compliance with provider licensing requirements).   
o 
Adverse events (AEs) - participants will be asked about the occurrence of AE/SAEs by 
their treatment provider at each visit. The AE protocol described in section 7, Safety and 
Assessments will be initiated and adhered to for all AEs identified.  
 
Weekly Follow-up  
Weekly outcomes will be collected electronically via direct patient self-report; participants who are 
unable to provide electronic data will be contacted directly by blinded study staff who will ascertain 
outcomes. Additional information related to data collection and quality assurance is described in section 
10.  
 
The following outcomes will be collected on a weekly basis for one year (± 2 days): 
o 
Primary outcomes 
▪ 
Pain intensity 
o 
Secondary outcomes 
▪ 
LBP frequency  
 
 

 
 
PACBACK Protocol V8 page 48 
      
Monthly Follow-up  
Monthly follow-up data (Months 1-12) will be collected electronically via direct patient self-report. 
Participants who are unable to provide electronic data will be contacted directly by blinded study staff 
who will ascertain outcomes, or they will be mailed a paper copy of the questionnaire to complete and 
return to the study team. Additional information related to data collection and quality assurance is 
described in section 10.  
 
The following outcomes will be collected on a monthly basis for one year (± 7 days): 
o 
Primary outcomes 
▪ 
Disability - Roland Morris Disability Questionnaire 
▪ 
Low Back Pain Impact - subset of PROMIS-29 
 
 
o 
Secondary outcomes 
▪ 
PROMIS measures, additional healthcare use, medication use, and productivity 
loss 
▪ 
AEs -participants will be queried about AEs associated with study interventions 
(e.g., increased pain, neurological symptoms, medication side effects etc.). 11 142 
143 The AE protocol described in section 7, Safety and Assessments will be 
initiated and adhered to for all AEs identified.  
Week 2 Follow-up 
In addition to outcomes collected weekly, the following outcomes will be collected at week 2 (± 7 days) 
o 
Psychosocial mediator measures 
▪ 
Measurement of key non-specific factors that may influence outcomes will be 
measured using the short forms for patient-provider connection (7-item), 
healthcare environment (6-item), and treatment expectancy (6-item) from the 
Healing Encounters and Attitudes Lists (HEAL) 
 
Month 1 Follow-up 
In addition to outcomes collected weekly and monthly, the following outcomes will be collected at month 
1 (between -7 and +14 days) 
o 
Psychosocial mediator measures 
▪ 
Measurement of key non-specific factors that may influence outcomes will be 
measured using the short forms for patient-provider connection (7-item), 
healthcare environment (6-item), treatment expectancy (6-item), and positive 
outlook (6-item) from the Healing Encounters and Attitudes Lists (HEAL) 
o 
Intervention uptake (SSM, SSM + SMT participants only) 
▪ 
To measure patient’s use of recommended activities we will document in patient 
self-report questionnaires the use of the main SSM components using the 
following question:  How many days in the past week did you use: the mind-
body skills (like relaxed breathing, progressive muscle relaxation) recommended 
by your provider; the exercises recommended by your provider; the postural 
awareness suggestions (like neutral spine) recommended by your provider; other 

 
 
PACBACK Protocol V8 page 49 
      
tips recommended by your provider (like suggestions for sleep, communicating 
with others, etc.); the workbook. 
o 
Telehealth Usability Questionnaire (TUQ) 
 
Month 2 Follow-up  
In addition to outcomes collected weekly and monthly, the following outcomes will be collected at month 
2 (between -7 and +14 days) 
o 
Low back physical exam objective outcome measures 
o 
Secondary outcomes 
▪ 
Patient satisfaction will be measured using a 7-point Likert scale (from 
completely satisfied to completely dissatisfied).144 
▪ 
Global improvement will be measured using a 9-point scale ranging from 
completely recovered to vastly worse.145 
▪ 
SBST status 
 
o 
Psychosocial mediator measures 
▪ 
Measurement of key non-specific factors that may influence outcomes will be 
measured using the short forms for positive outlook (6-item) from the Healing 
Encounters and Attitudes Lists (HEAL) . 
▪ 
Self-efficacy, Coping, Kinesiophobia, Pain Catastrophizing 
o 
Intervention uptake (SSM, SSM + SMT participants only) 
o 
COVID-19 impact & Telehealth Usability Questionnaire (TUQ) 
 
Month 6 Follow-up  
In addition to outcomes collected weekly and monthly, the following outcomes will be collected at month 
6 (between -7 and +14 days) 
o 
Secondary outcomes 
▪ 
Satisfaction, global improvement, chronic interference with daily activities and 
SBST status 
▪ 
Prevention of cLBP will be measured using the NIH RTF definition of 
cLBP “a back pain problem that has persisted at least 3 months and has 
resulted in pain on at least half of the days in the past 6 months.” 
Specifically, this will be assessed with NIH RTF minimum dataset items 1 
(LBP duration) and 2 (proportion of days that LBP has been a problem 
over the past 6 months).73 
 
o 
Intervention uptake (SSM, SSM+SMT participants only) 
o 
Psychosocial mediator measures 
▪ 
Self-efficacy, Coping, Kinesiophobia, Pain Catastrophizing, and HEAL positive 
outlook measure.  
o 
COVID-19 impact  
 

 
 
PACBACK Protocol V8 page 50 
      
6.2.5 
Completion/Final Evaluation 
Month 12 Follow-up  
In addition to outcomes collected weekly and monthly, the following outcomes will be collected at month 
12 (between -14 and +28 days) 
 
o 
Secondary outcomes 
▪ 
Satisfaction, global improvement, chronic interference with daily activities, 
visual trajectory questionnaire for pain 186 and SBST status 
▪ 
Chronic LBP status as determined by NIH RTF questions 
 
o 
Psychosocial mediator measures 
▪ 
Self-efficacy, Coping, Kinesiophobia, and Pain Catastrophizing measures 
▪ 
Measurement of key non-specific factors that may influence outcomes will be 
measured using the short form positive outlook (6-item) from the Healing 
Encounters and Attitudes Lists (HEAL) 
o 
Intervention uptake (SSM, SSM+SMT participants only) 
o 
COVID-19 impact  
o 
Participant Close-out 
▪ 
Final participation will be used to record participant status 
All efforts will be taken to facilitate participant’s completion of the study interventions. In the event a 
participant must discontinue the intervention early (see also Intervention Discontinuation), participants 
will be asked to complete follow-up electronic self-report questionnaires to the extent possible. Potential 
reasons for early termination include: 
 
● 
Participant develops a competing comorbid health condition that precludes adherence or makes it 
unsafe for them to proceed with their assigned treatment. 
● 
A change in the participant’s life (e.g., participant moves, dies, has other personal matters to 
attend).  
● 
Participant chooses to discontinue on their own for any reason (e.g., participant is not responding 
to care or getting worse). 
● 
Study closure by institute or oversight body. 
 
Additional information related to intervention discontinuation is described in Section 8. 
 
6.2.6  Additional Evaluation Related to Hybrid Effectiveness/Implementation Design, RE-AIM and 
PRECIS Frameworks 
 
Implementation Measures 
Mixed-methods data collection (qualitative and quantitative) will be used to collect contextual 
information addressing dimensions outlined by the RE-AIM framework. These data will inform future 
implementation and aid in the interpretation of effectiveness results.25 
 
Screening 

 
 
PACBACK Protocol V8 page 51 
      
● 
Qualitative survey questions (open-ended) will assess potential participants’ views regarding 
barriers and facilitators to participating in the study and study interventions.  
● 
Quantitative data regarding reasons for exclusion will also be collected 
 
Months 2, 6, and 12 Follow-Up  
● 
Qualitative surveys will address enrolled participants barriers and facilitators to engaging in the 
interventions as recommended, including barriers and facilitators for engaging in telehealth visits. 
● 
Satisfaction  
● 
HEAL Positive Outlook  
 
Additional contextual data will be collected from the participating practitioners to inform future 
implementation in other settings. Prior to training, prior to the start of the UG3 pilot phase, at the 
completion of the UG3 pilot phase, pre and post UH3 training, annually during the UH3, and at the 
completion of the UH3 randomized controlled trial, self-report questionnaires will be administered to all 
participating practitioners. Questionnaires will include qualitative survey questions that address 
practitioners’ views regarding the interventions, including perceived barriers and facilitators and their 
confidence in the interventions and in delivering care remotely189. The Pain Attitudes and Beliefs Scale 
(PABS)43 and additional questions regarding practitioner confidence (using a 0-10 NRS) will also be 
assessed quantitatively in the self-report questionnaires.  
 
Qualitative data will also be collected from purposeful samples of health providers’ and health system 
leaders using data collection methods that meet their needs and preferences (e.g., qualitative surveys, 
interviews and field notes). Additional details regarding assessment of implementation measure data 
collection is provided in the manual of operations.  
7. SAFETY ASSESSMENTS  
7.1 
Specification of Safety Parameters 
Following enrollment, participants will be asked about the occurrence of AE/SAEs by their treatment 
provider at every visit. In addition, participants will be informed to report AE/SAEs directly to study staff 
throughout the study period and will also be asked if they experienced any AE/SAEs associated with 
study interventions on monthly self-report surveys. Events will be followed for outcome information until 
resolution or stabilization. The PI or designee will record all reportable events with start dates occurring 
any time after enrollment until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study 
participation. 
7.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety 
Parameters 
Spinal manipulation therapy (SMT) is considered safe for the treatment of LBP, but side effects 
associated with SMT are common and benign. Approximately 50% of patients report one reaction, most 
commonly local discomfort that resolves within a day.7 99-102 SAEs following lumbar SMT are rare7 and 
are estimated to occur once per million to several million visits and include cauda equina syndrome, disc 
herniation, fracture, hematomas or hemorrhagic cysts.123  
 

 
 
PACBACK Protocol V8 page 52 
      
Risks associated with the supported self-management group are considered extremely rare. No SAEs were 
reported in trials including physical and biopsychosocial treatment components.7 Participants may 
experience emotional discomfort as a result of discussing the impacts of their pain (e.g., mood, social 
connections).  Participants may also experience physical discomfort as a result of the directional 
preference, postural awareness, and strengthening exercises. All of these side effects are expected to be 
temporary and short-lasting. 
 
Pharmacological therapies delivered as part of medical care are associated with increased AEs compared 
to placebo.7 Several protections are in place to minimize risks, including reminding participants to take 
their medication as prescribed and to contact the study clinician if there are changes to their medication 
regimens to avoid drug-drug adverse interactions. Also, clinicians will assess the potential for risk factors 
based on the patient’s medical history prior to prescribing/recommending (prescription and OTC) 
medications and will suggest the lowest effective dose(s) for the shortest time necessary. 
 
Below is an alphabetical list of expected AEs for each study intervention. 
 
Supported Self-Management 
● Emotional discomfort 
● Exacerbation of low back pain  
● New or increased leg pain 
● Numbness or tingling 
● Soreness or stiffness  
 
Medical Care 
● Allergic reaction 
● Cardiovascular symptoms: hypotension, edema, flushing,  
● Central nervous system: dizziness, weakness, ataxia, fatigue, drowsiness, headache, stimulation, 
insomnia, sedation, tremor, syncope 
● Chemical dependence 
● Dermatologic: itchy skin, rash, sweating 
● Endocrine & Metabolic: weight gain 
● Exacerbation of low back pain 
● Gastrointestinal symptoms: nausea, vomiting, dry mouth, abdominal pain, dyspepsia, diarrhea, 
GERD, constipation, bleeding 
● Kidney failure (excessive NSAIDs use) 
● Liver failure (excessive Acetaminophen use) 
● Ophthalmic: visual field loss, blurred vision  
● Respiratory: depression, arrest, apnea 
 
Spinal Manipulation Therapy 
● Cauda equina syndrome 
● Disc herniation 
● Exacerbation of low back pain 
● Fracture 
● Hematoma 
● Hemorrhagic cyst 
● New or increased leg pain 
● Numbness or tingling 
● Soreness or stiffness  
 

 
 
PACBACK Protocol V8 page 53 
      
7.3 
Adverse Events (AEs) and Serious Adverse Events (SAEs) 
AE is generally defined as any unfavorable and unintended diagnosis, symptom, sign (including an 
abnormal laboratory finding), syndrome or disease which either occurs during the study, having been 
absent at baseline, or if present at baseline, appears to worsen. AEs are to be recorded regardless of their 
relationship to the study intervention.   
 
The following scale will be used to grade AEs: 
1.  Mild: no intervention required; no impact on activities of daily living (ADL). 
2.  Moderate: minimal, local, or non-invasive intervention indicated; moderate impact on ADL. 
3.  Severe: significant symptoms requiring invasive intervention; subject seeks medical attention, needs 
major assistance with ADL. 
 
We will measure and compare rates of AEs across the four treatment arms. We will specifically look for 
common treatment-related AEs that include: LBP, soreness at the treatment site, gastrointestinal 
symptoms, emotional discomfort, and other events. We will capture AEs prospectively from study 
participants through monthly surveys and at in-person/videoconference/telephone visits. Each unique 
occurrence will receive a separate ID in order to avoid duplication in documentation. 
 
SAE is generally defined as any untoward medical occurrence that results in death, is life threatening, 
requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or 
significant disability/incapacity, or is a congenital anomaly or birth defect. 
 
We will collect SAEs both passively through ad hoc reporting and through systematic evaluation at study 
visits. Given the nature of the interventions we do not anticipate any specific treatment-related SAEs and 
therefore focus on standard and LBP-specific serious events: death; severe or permanent disabilities; life-
threatening conditions; hospitalizations; other important medical events; progressive neurological deficits, 
or cauda equina syndrome.  
 
     7.4 Reporting Procedures 
Procedures and responsibilities for reporting AEs and SAEs are outlined in the figure below. 
“Awareness” in the figure below is defined as the date at which the research team is able to contact the 
participant to gather additional information about the event.   

 
 
PACBACK Protocol V8 page 54 
      
 
 
If an AE occurs at a CCC where the PI is not available, the PI at the other CCC institution will be notified 
and the AE reporting protocol will be initiated. If both PIs are not available, a clinical Co-Investigator 

 
 
PACBACK Protocol V8 page 55 
      
will be notified, and the above protocol will be initiated. Once a PI is available, the PI will assume 
responsibility for reporting.   
7.5 
Follow-up for Adverse Events 
AEs/SAEs will be identified during the intervention phase at study visits and during the study follow-up 
phase using monthly self-report questionnaires (surveys) or through direct contact with study staff. Events 
will be followed until resolution or stabilization, whichever occurs first; resolution and stabilization will 
be determined by the PI with input from the study clinician when appropriate.  
 
If an AE/SAE occurs during the intervention phase, the study clinician will monitor the AE/SAE while 
the participant is under their care, this will include a medical evaluation and treatment, or modifications to 
treatment as necessary to protect the participant and minimize harm. If warranted, referral to an outside 
provider will be made.  
 
If an AE/SAE occurs during the follow-up phase, study staff will be in regular contact with the participant 
as the event permits.  
7.6 
Safety Monitoring  
A data safety monitoring board (DSMB) will be created to review the accruing data quarterly to:  
 
1) Ensure that the study is adequately enrolling 
2) Ensure data acquisition and protocol adherence rates are acceptable 
3) Ensure that there are no serious safety concerns.  
 
The DSMB will be assigned by NCCIH in coordination with the DCC. SAEs will be brought to the 
attention of the IRB and the DSMB in writing. As part of the Data Safety and Monitoring Plan (DSMP) 
we will perform continuous and interim analysis of accruing safety data. We have defined potentially 
treatment related SAEs (SAEs) that will be monitored throughout the course of the study.  
 
The following guidelines will be used when considering halting the trial for safety: 1) > 5% of 
participants experience an unexpected, related, moderate or greater adverse event; 2) ≥2% SAE overall 
that are unexpected and related to the intervention. The DSMB will consider this guidance when making 
recommendations regarding trial continuation.  
8. INTERVENTION DISCONTINUATION  
Criteria for Discontinuation 
Participants will be discontinued from their assigned intervention if the study interventions become 
contraindicated, for example: 
● A serious adverse event related to treatment occurs and thus makes it unsafe to continue 
with the assigned intervention. 
● The participant has a specific cause of back pain and was erroneously diagnosed during 
screening.  
● New evidence emerges and suggests it is unsafe for the participant to proceed with the 
intervention. 
 
Due to the pragmatic nature of this study, interventions can be modified to accommodate patients and 
their needs (e.g., mobilization can be used in lieu of manipulation, or medication changes can be made in 
the medical care group to mitigate drug-induced side effects).  

 
 
PACBACK Protocol V8 page 56 
      
 
Criteria for discontinuation are met when the event is classified as serious and it is determined by the 
provider and/or the PI that it is unsafe to continue with the study intervention, or when a diagnosis for a 
specific cause of LBP is made. 
 
Reasons for Discontinuation 
All efforts will be taken to facilitate participant’s completion of the study interventions. Potential reasons 
for early termination include: 
● Participant develops a competing comorbid health condition that precludes adherence or makes it 
unsafe for them to proceed with their assigned treatment. 
● A change in the participant’s life (e.g., participant moves, dies, has other personal matters to 
attend).  
● Participant chooses to discontinue on their own for any reason (e.g., participant is not responding 
to care or getting worse). 
● Study closure by institute or oversight body. 
 
With their permission, participants will continue to be followed if the study intervention is discontinued. 
Participants who have discontinued treatment will be asked to complete weekly and monthly self-report 
questionnaires (months 1-12), if possible. Efforts will be made to accommodate participant compliance 
(e.g., paper or electronic questionnaires, or data can be collected by phone).   
 
If participants are unwilling to complete the entire self-report questionnaires during the follow-up phase, 
they will be asked to complete the primary outcome measures (e.g., pain intensity and frequency, low 
back disability) on a monthly basis. This can be further modified to include, at a minimum, measures at 2, 
6 and 12 months.  
 
Temporary Discontinuation of the Intervention 
Potential reasons for temporary intervention discontinuation include: 
● An acute health problem arises and prohibits their ability to attend the intervention (e.g., 
hospitalization). The length of discontinuation will be addressed on a case-by-case basis. All 
attempts will be made to minimize this discontinuation.  
● Participant has a scheduled vacation. Participants will be asked to limit their vacation time to 1 
week.  
9. STATISTICAL CONSIDERATIONS  
 
Modifications to Statistical Analysis Plan Regarding the Sample Size and Power 
(edited February 2023) 
 
In consultation with NCCIH program staff and the DSMB in December 2022 we have modified 
the target enrollment to n=1000 participants (reduced from original n=1180). Our rationale for 
the modification is based on alignment with our updated primary outcome on chronicity. We 
have conducted extensive evaluation of power to detect meaningful effects using the LBP-Impact 
measure and our other primary outcomes.  We have determined that it is appropriate to reduce 
the target sample size. 
 
Modifications to Statistical Analysis Plan Regarding Primary Analysis and Treatment of 
Multiple Comparisons 

 
 
PACBACK Protocol V8 page 57 
      
(edited September 2022) 
 
The trial initially had three main effectiveness objectives: (1) prevention of chronic LBP at 
twelve months; (2) recovery from acute/sub-acute LBP at six months; (3) Average of pain and 
disability over twelve months. In 2021, the NIH statistician overseeing the trial raised the 
question of the adequacy of the planned adjustment for multiplicity given the trial’s three main 
effectiveness objectives and accompanying four primary outcome measures. In response to this 
concern, the lead investigators recommended the recovery objective be changed to a key 
secondary outcome. Early in the conduct of the trial it was decided and approved as a protocol 
change to include patients that had an acute aggravation of ongoing LBP, if the ongoing pain was 
not rated as severe in the month prior to the aggravation. This protocol change substantially 
lowers the proportion of patients that can be expected to recover according to our criteria (pain 
severity = 0 and RMD score ≤ 2). Given this change, the recovery outcome was less appropriate 
as a primary effectiveness objective and demoting it to a secondary outcome mitigates the 
concern of cross-objective control.  
 
In consultation with NCCIH program staff and the DSMB in 2022 we have outlined our planned 
publications for presenting our main results and have revised the primary statistical test that 
would be used to evaluate differences in mean outcomes across the treatment groups.  
Specifically, rather than conduct individual tests of SMT alone, SSM alone, and the combination 
against medical care with adoption of a multiple comparisons correction for three tests we will 
now use an overall test of equality across the four groups to conduct a single omnibus hypothesis 
test followed by the estimation of key group comparisons using Fishers least significant 
difference methods to construct individual nominal 95% confidence intervals with reporting of 
the induced simultaneous coverage.  These methods will be used for primary analysis of the 3 
primary effectiveness outcomes : LBP-Impact and pain and disability. 
 
We plan to present principal findings in two key publications.  The first publication would focus 
on average pain and disability over 1-year as the multiple primary outcomes and present 
recovery at 6-months (previously a primary outcome ) as one of the secondary outcomes.  A 
second paper will focus on LBP Impact averaged over months 10-12 as the primary outcome . 
 
Modifications to Statistical Analysis Plan Regarding Primary Outcome 
(edited July 2021) 
 
In consultation with the NCCIH program staff and DSMB in the Spring of 2021 we have 
changed our primary outcome for assessment of treatment impacts on chronicity prevention.  
Specifically, we have replaced our original NIH Task Force on Research Standards for Chronic 
LBP (referred to as RTF) dichotomous chronicity measure with the RTF quantitative impact 
measure.  The LBP-Impact outcome measure is a subset of the Promise 29 measures, which is 
already being collected at baseline and every month during the follow-up year from the 
start of the trial. As a secondary outcome measure, we will compare differences across 
treatment groups in the distribution of patients with mild, moderate, and severe impact.  
 
Modifications to Statistical Analysis Plan in Response to COVID-19 Impacts  
(edited August 2020) 

 
 
PACBACK Protocol V8 page 58 
      
 
In Spring 2020 we suspended new enrollment into our study due to the COVID-19 pandemic.  
We continue to follow our participants and to maintain high-quality data collection.  In order to 
resume trial enrollment, we are making adjustments to both care delivery and research data 
collection, and we have a modification to the enrollment and randomization that is responsive to 
risk mitigation.  The key design and analysis modifications include: 
• We will initially restart with restricted randomization to the MC and SSM groups. We 
will resume full factorial randomization once it is safe and appropriate. Specifically, in 
order to restrict physical interaction, we will conduct both remote assessment and 
intervention in a partial randomization period during which participants are randomized 
only to Medical Care (MC) or Supported Self-Management (SSM). Although we hope 
that partial randomization will only occur for the Fall of 2020, we recognize the need to 
be flexible by being able to consider reverting to restricted partial randomization during 
any future periods when physical contact is precluded.  Since all possible randomization 
groups contribute to the ultimate effect estimates, the partial randomization period data is 
informative and can be combined with the pre-COVID data and the full factorial 
randomization data.  In order to account for potential period-effects, we will modify all 
analyses to include adjustment for partial randomization time periods. 
• Our statistical analysis will now adjust for study period (PERIOD) which is appropriate 
to account for our initial trial phase (UG3 and UH3 before March 2020), our restricted 
randomization phase, and resumption of full factorial randomization. 
• Although we will ultimately have more subjects enrolled into the UMC and SSM groups 
due to restricted randomization we will not change our parameter of interest which is 
defined as the linear contrast capturing the equally weighted average of the SSM 
intervention effect combined from no-SMT and SMT strata, and similarly the equally 
weighted average of the SMT intervention effect combined from the no-SSM and SMM 
strata. (please see below for details) 
• We have evaluated the impact on the power of our study subject to the potential for up to 
240 subjects enrolled during restricted randomization.  In our original protocol we 
focused sample size on obtaining adequate power for the Aim 1 chronicity endpoint 
assuming treatment relative risks of 0.70 (a 30% relative reduction), no interaction 
between treatments, and a control rate of 0.20.  For this original scenario we used 
simulations to compute a power of 81% for either the overall SSM effect or the overall 
SMT effect.  With partial randomization and an upper bound of n=240 subjects allocated 
during this period we obtain 78% power to detect an overall SSM effect and 77% power 
to detect an overall SMT effect.  Therefore, the impact of altering the design to permit 
partial randomization is anticipated to have a minor reduction in power for our binary 
endpoints.  In addition, the planned design will result in a minimum of n=30 per protocol 
pre-COVID subjects in the SMT and SSM+SMT groups combined with a full factorial 
randomization allocation of n=188 will permit a total of n=30+188=218 subject per group 
to evaluate mean differences in pain and disability scales across the four treatment 
groups.  For MC and SSM groups we expect to have an upper bound of n=45 pre-
COVID, n=120 partial randomization, and n=188 full factorial randomization subjects or 
n=45+120+188=354 total subjects per group.  Our original balanced allocation would 
have produced n=1180/4= 295 subjects/group.   
 

 
 
PACBACK Protocol V8 page 59 
      
Statistical Analysis Plan 
 
Introduction: A factorial trial is ideal when the two treatments under study are thought to act 
independently via different mechanisms .146 Our interventions focus on a physical treatment 
approach (SMT) and a psychological intervention (SSM) for addressing acute LBP. A factorial 
design allows an efficient evaluation of each of these modalities using fewer subjects than would 
be required by separate trials. In addition, a crucial advantage of a factorial trial is the ability to 
evaluate whether the beneficial effects of each treatment modality combine in an additive, 
antagonistic, or synergistic fashion through evaluation of treatment interaction.147  
 
The trial was originally powered to detect meaningful differences in two dichotomous primary 
outcome measures, chronicity and recovery. These two outcomes are now secondary 
effectiveness measures.   
For the 3 quantitative primary outcomes collected 
longitudinally, RMDQ, Pain NRS and LBP-Impact 
we will conduct detailed analysis of the four groups 
formed by the factorial design since we have 
excellent power for such endpoints with our revised 
sample size of 1000 subjects. However, McAlister et 
al.146 comment that “the most powerful analysis of a 
factorial trial is performed at the margins” and we 
adopt such an approach for our secondary binary 
chronicity and recovery outcomes. We explicitly 
define the separate treatment effects for SMT and 
SSM as the overall or average treatment effect that is 
obtained from pooling comparisons over strata 
defined by the other treatment approach (i.e., the 
SMT treatment effect obtained by pooling over strata 
with and without SSM). In particular, we define the parameter of interest as a linear combination 
(contrast) of parameters from an appropriate regression model that acknowledges the potential 
for SMT and SSM interaction. Therefore, our proposed analyses for binary outcomes do not 
make any additive assumptions and is quite generally valid for creating meaningful overall effect 
summaries. Furthermore, by collecting detailed outcomes and health care utilization through one 
year we can conduct thorough mediation analyses and careful evaluation of concomitant 
treatment. 
 
Our statistical analysis plan focuses on the effectiveness evaluation detailed under the Primary 
Objective in the protocol, We also provide a plan for mixed methods analyses 
(qualitative/quantitative) associated with the Secondary Objective: implementation. 
 
Primary Effectiveness Outcome # 1: prevention of cLBP that is impactful at 10-12 months follow-
up (LBP Impact scale (min 8 - max 50) using mean from months 10-12). The LBP impact scale includes 
measures of pain intensity, pain interference, and physical function from the PROMIS-29 Profile v2.0) we 
will determine the effectiveness of SMT, SSM, and the combination of SMT+SSM relative to 
medical care (MC) 
 
Figure 9.1: The 2x2 factorial design 
(n=1000) 
 

 
 
PACBACK Protocol V8 page 60 
      
LBP Impact Effectiveness Hypothesis: SMT alone will decrease the impact of low back pain 
with at least a moderate effect size of 0.3 standard deviations (Cohen’s d). Similarly, SSM alone 
will decrease the impact of low back pain with at least a moderate effect size of 0.3 standard 
deviations. The combination SMT+SSM will lead to a stronger but not necessarily additive net 
reduction compared to the individual component interventions.  
 
Design: As shown in Figure 9.1, we plan to enroll a total of 1000 subjects randomized to one of 
four treatment groups using a factorial design:  medical care (MC); spinal manipulation therapy 
alone (SMT); supported self-management alone (SSM); and combined SMT+SSM. 
 
LBP Impact Primary Analysis: Our primary analysis will compare each of the treatment groups 
to MC using an adjusted regression analysis.  Specifically, Let Yij denote the primary outcome 
variable (average of LBP-Impact over months 10-12) for subject i in site j, and let Site(2) be an 
indicator variable used to code the two recruitment sites. All analyses will adjust for site and the 
baseline risk status represented by RiskGroup (0=medium risk; 1=high risk). In order to code the 
treatment groups we use the variables SMT-Only (0=no; 1=only spinal manipulation therapy), 
SSM-Only (0=no; 1=only supported self-management), and SMT-and-SSM (0=no, 1=both SMT 
and SSM). Given interruption by COVID-19 and an associated period of restricted 
randomization we will also adjust for this modified randomization using the variables Period(k) 
which will be an indicator for: 1=UG3 and UH3 through March 2020; 2=calendar period of 
restricted randomization; and 3=calendar period of resumed full factorial randomization. We will 
use an adjusted linear regression model with robust standard error to make inference regarding 
treatment groups using the following structure where Xij denotes the covariates for subject i:  
 
E( Yij  | Xij ) = 𝛽0 +   𝛽1 ⋅ Site(2)j +  𝛽2 ⋅ RiskGroupij + 
𝛽3⋅ SMT-Onlyij + 𝛽4 ⋅ SSM-Onlyij + 𝛽5 ⋅ SMT-and-SSMij +  
𝛽6 ⋅ Period(2)ij + 𝛽7 ⋅ Period(3)ij 
 
In the primary regression model the parameters of interest are: 
 
𝛽3 = adjusted mean difference comparing SMT Only to UMC; 
 
𝛽4 = adjusted mean difference comparing SSM Only to UMC; 
 
𝛽5 = adjusted mean difference comparing combined SMT and SSM to UMC. 
Our primary analysis will test the global hypothesis that these three treatment comparisons are all 
null using a multivariate Wald test with 3 degrees of freedom and alpha=0.05. We will then 
provide individual confidence intervals for each coefficient that compares an intervention group 
to medical care based on Fishers least significant difference methods which provide individual 
nominal 95% confidence intervals and also estimates the simultaneous coverage probability.  
 
Power and Sample Size for Primary Outcome of LBP Impact: To characterize the power of our 
primary analysis (an overall F-test) we provide a summary table that considers potential 
standardized mean differences comparing the individual intervention arms to medical care.  For a 
small effect size (Cohen’s d of 0.2) and an additive effect we have greater than 90% power to 
reject the null.  However, additivity may not hold so we also consider sub-additive scenarios, and 
the scenario where only one intervention is effective.  For small to moderate effect sizes (0.2 – 
0.3 standard deviations) we have >90% with our proposed design. We assume n=1000 enrolled 
with a realistic 90% follow-up that yields 900 evaluated subjects. We also account for the 

 
 
PACBACK Protocol V8 page 61 
      
imbalanced design due to restricted randomization that will yield approximately 300 subjects in 
the UMC and SSM alone groups and 200 subjects in each of the SMT and SMT+SSM groups. 
Power is calculated based on 5,000 simulation replications for each scenario and presented in 
Table 9.1. 
 
The current design is robust to the enrollment target and follow-up assumptions.  For example, 
with an enrollment of n=1000 subjects and 85% follow-up we would have 90% power for our 
expected alternative scenario with small treatment effects (0.30 standardized mean difference) 
that are not additive (sub-additive 1).  
 
A secondary evaluation will consider whether the separate effects of SMT and SSM are 
potentially additive and this will be done using a formal test for interaction:  
 
Interaction Model:  
E( Yij  | Xij ) = 𝛽0 +   𝛽1 ⋅ Site(2)j +  𝛽2 ⋅ RiskGroupij + 
𝛽3⋅ SMTij + 𝛽4 ⋅ SSMij + 𝛽5 ⋅ SMTij ⋅ SSMij +  
𝛽6 ⋅ Period(2)ij + 𝛽7 ⋅ Period(3)ij 
 
    
In this model a test of H0: β5=0 
allows us to determine if there is 
strong evidence for synergistic or 
antagonistic effects associated with 
combined treatment. 
 
Secondary Effectiveness Outcome 
of Chronicity: Chronic back pain: 
For a subject to be classified as a 
chronic back pain patient at the 1-year 
assessment they must endorse having 
“a back pain problem that has 
persisted at least 3 months and has 
resulted in pain on at least half of the 
days in the past 6 months”. This 
outcome is based on specific items 
from the NIH Research Task Force recommended minimal data set:73 Question 1 on LBP 
duration; and Question 2 on the proportion of days that LBP has been a problem in the past 6 
months. To evaluate chronic back pain we will consider the 1-year status as a key secondary 
outcome for chronicity prevention, and will use the 6-month status as another key secondary 
outcome. 
 
Chronicity  Hypothesis: SMT alone will decrease the rate of cLBP by 6-9% from a baseline 
MC level anticipated to be 20% or higher. Similarly, SSM alone will decrease the rate of cLBP 
by 6-9%, and the combination of SMT+SSM will lead to an additive net reduction.  
 
Secondary Chronicity outcome Analysis: The analysis of the secondary binary outcome will use 
parallel marginalized tests of the average SMT treatment effect and the average SSM treatment 
Table 9.1: Chronicity based on LBP-Impact averaged over months 10-
12 of follow-up.  Power for the overall F-test of equality of means under 
various alternative scenarios. (alpha = 0.05) 
Alternative 
SMT 
Alone 
SSM 
Alone 
SMT 
+ 
SSM 
Power 
Additive 
0.20 
0.20 
0.40 
93% 
Sub-Additive 1 
0.25 
0.25 
0.35 
91% 
Sub-Additive 2 
0.30 
0.30 
0.30 
94% 
Sub-Additive 3 
0.25 
0.25 
0.25 
81% 
Single effect 1a 
0 
0.30 
0.30 
98% 
Single effect 1b 
0.30 
0 
0.30 
94% 
Single effect 2a 
0 
0.25 
0.25 
91% 
Single effect 2b 
0.25 
0 
0.25 
80% 

 
 
PACBACK Protocol V8 page 62 
      
effect using linear contrasts from a logistic regression model. Specifically, we will use two 
separate Wald tests based on logistic regression, with stratification by recruitment site and 
baseline risk group (medium, high). Let Yij denote the primary outcome status (0=not chronic; 
1=chronic) for subject i in site j, and let Site(2) be an indicator variable used to code the two 
recruitment sites. All analyses will adjust for site and the baseline risk status represented by 
RiskGroup (0=medium risk; 1=high risk). In order to code the treatment groups we use the 
variables SMT (0=no; 1=spinal manipulation therapy), and SSM (0=no; 1=supported self-
management). Given interruption by COVID-19 and period of restricted randomization we will 
adjust for this using the variables Period(k) which will be an indicator for: 1=UG3 and UH3 
through March 2020; 2=calendar period of restricted randomization; and 3=calendar period of 
resumed full factorial randomization. Regression models for the outcome are used to structure 
the probability of chronic back pain as follows:  
 
  Additive Model 
 logit[ P(Yij =1 | Xij) ] =  𝛽0 + 𝛽1⋅ Site(2)j +𝛽2⋅ RiskGroupij + 
𝛽3⋅ SMTij + 𝛽4⋅ SSMij +  
𝛽5⋅ Period(2)ij +  𝛽6⋅ Period(3)ij 
 
  Full Model  
logit[ P(Yij =1) ] =  𝛽0 + 𝛽1⋅ Site(2)j +𝛽2⋅ RiskGroupij + 
𝛽3⋅ SMTij + 𝛽4⋅ SSMij + 𝛽5 ⋅ SSMij ⋅ SMTij +  
𝛽6⋅ Period(2)ij +  𝛽7⋅ Period(3)ij 
 
 
Our original application proposed using an additive model to generate a single summary 
parameter that describes the SMT effect (β3) and the independent SSM effect (β4). However, the 
additive model uses an assumption that the effect of one intervention is independent of whether 
the other intervention is delivered. Such an assumption is not necessary, and a full model can be 
used to make inference on a single linear contrast for each treatment that represents an average 
treatment effect. 
 
The “Full Model” can then be used to derive an overall or average effect of SMT, and an overall 
or average effect of SSM. Specifically, focusing on the effect of SMT the model yields: 
 
SMT effect when SSM=0:  
 
β3 
 
SMT effect when SSM=1:  
 
β3 + β5 
 
Average SMT effect:  
 
½ β3 + ½ (β3 + β5) = β3 + ½ β5 
 
Our original analysis plan used an additive regression model that did not include the interaction 
term in order to generate a model-based average effect of SMT. By using the full model, we are 
not making any assumption of constancy of SMT effect across the two strata defined by SSM, 
and are directly calculating the average of the two treatment effects as the linear contrast that will 
be used to summarize the overall effect of SMT. The model can similarly be used to derive a 
linear contrast the represents the average SSM effect: 
 
SSM effect when SMT=0:  
 
β4 
 
SSM effect when SMT=1:  
 
β4 + β5 
 
Average SSM effect:  
 
½ β4 + ½ (β4 + β5) = β4 + ½ β5 

 
 
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The overall SMT summary (β3 + ½ β5) estimates a common or average effect of SMT by 
pooling across sites, across risk groups, and across the two SSM arms (see figure 9.2). Similarly, 
β4 + ½ β5 estimates a common or average effect of SSM by pooling over the site, risk group, 
and SMT strata. Such analysis leverages the factorial design to permit separate estimates for each 
component of intervention. Notice that an additive model would use only 2 coefficient 
parameters to code the four treatment groups by assuming that the combined SMT+SSM group 
will have a treatment effect that is the sum of the effect for each individual component. Our 
analysis does not make any additive assumptions but rather directly defines a summary contrast 
for each treatment modality as the parameter of interest. Factorial designs are particularly 
efficient when evaluating two treatment modalities that work in complementary domains such as 
SMT (physical) and SSM (psychological) and permit separate assessment of each intervention. 
Formally, our primary analysis will separately test the null hypothesis H0: (β3 + ½ β5) = 0 
denoting no average effect of SMT, and H0:(β4 + ½ β5) = 0 denoting no average effect of SSM. 
Each primary test will use a significance level of 0.05 without correction since each test 
evaluates a separate intervention. Finally, evaluation of the interaction term using SMTij ⋅ SSMij 
permits a formal evaluation for non-additivity by testing the interaction coefficient H0: β5=0 
(interaction model described below).  
 
Power and Sample Size for Secondary Outcome of Chronicity: In order to determine the 
necessary sample size for effectiveness evaluation we need to formulate assumptions for the 
binary secondary outcome rate in the treated and untreated groups. Chou and Shekelle34 review 
six studies conducted in primary care that focused on pain, functional status, or mixed outcomes. 
Using results from this paper we conservatively assume a rate of cLBP of 20% at 1 year. In order 
to formulate appropriate effect estimates we consider detection of a relative risk of RR=0.70 for 
each of SMT and SSM individually implying a reduction of the rate from 20% to 14% for these 
intervention groups. Based on the Cochrane Back Review Group148 a relative risk of 0.70 is a 
clinically relevant and medium in size intervention effect, while the assumption of additive 
effects on the probability scale would lead to a cLBP rate of 8% among those randomized to 
SMT+SSM, which is considered a “large” treatment effect (RR=0.40). Therefore, we seek to 
design our study to detect and medium sized treatment effects, and consider power under a 
collection of plausible scenarios. A recent cohort study of acute LBP patients in primary care 
reported a similar proportion of patients with cLBP at 2 years, but noted the estimate varied 
based on the case definition149 and estimates based on the NIH RTF definition are not yet 
available. Relative to general LBP patients, we expect a rate of chronicity in the MC group to be 
larger since we are enrolling subjects at an increased risk of chronicity. Accordingly, we 
increased the estimated proportion with cLBP in the MC group to be 30 and 40% and determined 
the magnitude of treatment effects for which we have ≥ 80% power. At 1 year, we assume that 
we will have at least 88% follow-up based on prior studies conducted at the clinical research 
sites and studies11 150 with similar incentives151.  Thus, with n=1000 enrolled subjects we expect 
at least n=880 total subjects available for primary analysis.  
 
Our original sample size was chosen as n=1180 (since modified to n=1000) to ensure 80% power 
assuming an additive model with a chronic rate of 20% in UMC and a medium relative risk (RR) 
of 0.70. To evaluate power we conducted simulations using the R statistical package. We 
generated data under various additive assumptions. For analysis we first considered a single 

 
 
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likelihood ratio test of one treatment modality (either SMT or SSM). For simulations we 
considered crude analysis while our formal analysis will additionally adjust for site and baseline 
risk and therefore improve power since these are variables that only predict outcome and are not 
related to treatment group. For each scenario we simulated 5,000 data sets and empirically 
calculated power as the percentage of replicates in which the null hypothesis was rejected. 
 
Using simulations with n=1000 subjects, 90% follow-up, and accounting for our imbalanced 
allocation due to COVID interruption we compute power for analyses that consider individual 
marginal treatment effects for both SMT and SSM. If we assume a UMC chronicity rate of 20% 
and a relative risk of 0.65 (rate under treatment = 20% * 0.65 = 13%, or an absolute risk 
reduction of 7%) then we have >85% power to detect average SSM or SMT effects.  If we a 
smaller effect corresponding to a relative risk of 0.70 (rate under treatment = 20% * 0.70 = 13%, 
or an absolute risk reduction of 7%) then we have approximately 70% power to detect average 
SSM or SMT effects of this magnitude (specifically accounting for imbalance power is 72% for 
SSM and 70% for SMT).  Power is greater for any relative risk when the UMC rate is increased 
to 30% or 40%. These relative risk effect sizes equate to medium effect sizes and are considered 
clinically important by Cochrane’s Back Review Group.148 We have not powered the study to 
detect interaction for the binary chronicity endpoint, but rather have powered the study to detect 
interaction on the underlying function and disability scales (see below). 
 
Furthermore, we have excellent power to detect interaction effects where the effect of SMT and 
SSM may be synergistic or antagonistic, and using alpha=0.05 we have >80% to detect a X-point 
difference in LBP Impact treatment effects of one modality across the strata defined by the other 
treatment modality. 
 
Secondary Effectiveness Outcome of Recovery: Determine the effectiveness of SMT, SSM, 
and the combination of SMT+SSM relative to medical care (UMC) in promoting recovery from 
acute or subacute LBP at 6 months. 
 
In 2021, the NIH statistician overseeing the trial raised the question of the adequacy of the 
planned adjustment for multiplicity given the trial’s three main effectiveness objectives and 
accompanying four co-primary outcome measures. In response to this concern, the lead 
investigators recommended the recovery objective be changed to a key secondary outcome. 
Early in the conduct of the trial it was decided and approved as a protocol change to include 
patients that had an acute aggravation of ongoing LBP, if the ongoing pain was not rated as 
severe in the month prior to the aggravation. This protocol change substantially lowers the 
proportion of patients that can be expected to recover according to our criteria (pain severity = 0 
and RMD score ≤ 2). Given this change, the recovery outcome was less appropriate as a primary 
effectiveness objective and demoting it to a secondary outcome mitigates the concern of cross-
objective multiplicity control. 
 
In 2022 NCCIH and the DSMB approved that the recovery effectiveness objective, 
formally one of the 3 primary effectiveness objectives, will be designated as a key 
secondary outcome. 
 

 
 
PACBACK Protocol V8 page 65 
      
Recovery Effectiveness Hypothesis: SMT alone will increase the rate of recovery by 5.5-7.5% 
or more from a baseline MC rate of 5%-15%. Similarly, SSM alone will increase the rate of 
recovery from 5.5-7.5%, and the combination of SMT+SSM will lead to an additive net increase 
in the recovery rate. 
 
Recovery outcome definition: For a patient to be classified as recovered at the 6 month or 1 
year assessment they must endorse both an NRS of 0, and an RMDQ of <= 2.152 To evaluate 
recovery we will consider the 6-month status first and use the 1-year status second.  
 
Recovery Analysis: The primary analysis will be two parallel tests of the average effects of SMT 
and SSM in a full logistic regression model for the primary outcome (recovery at 6 months). The 
primary analysis for recovery will use pre-specified linear contrasts for hypothesis testing 
regarding overall or average effects. 
 
Power and Sample Size for the Recovery Outcome: In order to determine the necessary sample 
size for effectiveness evaluation we need to formulate assumptions for the primary outcome rate 
in the treatment and control groups. Bronfort et al.11 compared SMT plus Home Exercise with 
Advice (HEA) to HEA alone among subacute and chronic patients and find complete recovery 
from leg pain in 20% of SMT+HEA versus 5% of HEA at 12 weeks, and 23% versus 12.5% 
respectively at one year (RR=1.84) providing evidence that relative risks in the range of 1.5-2.0 
are plausible. The recovery rate at 6 months was estimated based on studies by Kamper et al.152 
and members of our investigative team,153 which used the same strict definition for recovery. 
Kamper et al.152 summarize recovery rates and criteria based on both NRS and RMDQ from four 
studies with acute and subacute subjects. Recovery rates range from 7% to 12%. A recent study 
by George et al.153 reported a 5% recovery rate within a mixed population of sub-acute and 
chronic patients with increased risk for 
cLBP. Given the potential uncertainty 
in the recovery rate for the MC group, 
we varied the expected recovery rate 
from 5-15% and determined the 
magnitude of treatment effects for 
which we have ≥80% power.  
 
For simulations we considered crude 
analysis while our formal analysis will 
additionally adjust for site and 
baseline risk yielding improved power 
since these are variables that only 
predict outcome and are not related to 
treatment group. For each scenario we 
simulated 5,000 data sets and 
empirically calculated power as the 
percentage of replicates in which the 
null hypothesis was rejected.  
 
 
Figure 9.2: Power of a single marginal treatment effect 
test as a function of relative risk (assumed equal for SMT 
and SSM), and recovery rate with UMC. 
 
1.4
1.6
1.8
2.0
50
60
70
80
90
100
Relative Risk
power
rate = 15 %
rate = 10 %
rate =  5 %
RD=8.3%
RD=7.5%
RD=5.5%

 
 
PACBACK Protocol V8 page 66 
      
Figure 9.2 shows the power to test each intervention marginally. We see that we have >80% 
power to detect a relative risk of 1.75 associated with either SMT or SSM if the UMC recovery 
rate is 10%. If the UMC recovery rate is 5% then we have power to detect a 5.5% risk difference 
(RR=2.1), while if the UMC recovery rate is 15% then we have power to detect an 8.3% risk 
difference (RR=1.55). These effects are also medium in size and considered clinically important 
by Cochrane’s Back Review Group.148   
 
Primary Effectiveness Outcome # 2 and 3: Determine the effectiveness of SMT, SSM, and the 
combination of SMT+SSM relative to medical care (MC) in achieving improvements in average 
pain intensity and back-specific functioning cumulative through 1 year based on monthly 
measures of RMDQ and weekly Pain NRS scores. 
 
Effectiveness Hypothesis: We will focus on parallel analyses for pain and function. We 
hypothesize that SMT alone will decrease average pain by at least 1 point, and average disability 
by 2 points. Similarly, SSM alone will decrease average pain by at least 1 point, and average 
disability by 2 points, and the combination of SMT+SSM will lead to an sub-additive net 
decrease of <2 points and <4 points respectively. 
 
Primary outcome variables: We will derive measure of disability and pain by calculating the 
time-averaged patient outcome using the monthly measurements taken over the year of follow-
up. 
 
Primary Analysis: For quantitative outcomes we will focus on analyses that generally do not 
assume that the effects of SMT and SSM are additive since we have adequate power to evaluate 
specific group contrasts. We will use linear regression methods with robust standard errors to test 
for the difference in mean scores comparing each intervention group to MC. Let Yij denote the 
outcome of interest (either average pain or average disability for parallel analyses). Similar to 
our primary analysis of LBP impact 1 we will use a linear regression model with robust standard 
errors using the structure: 
    
 
Four Groups Model:  E( Yij  | Xij ) = 𝛽0 +   𝛽1 ⋅ Site(2)j +  𝛽2 ⋅ RiskGroupij + 
𝛽3⋅ SMT-Onlyij + 𝛽4 ⋅ SSM-Onlyij + 𝛽5 ⋅ SMT-and-SSMij +  
𝛽6 ⋅ Period(2)ij + 𝛽7 ⋅ Period(3)ij 
 
In the primary regression model the parameters of interest are: 
 
𝛽3 = adjusted mean difference comparing SMT Only to UMC; 
 
𝛽4 = adjusted mean difference comparing SMT Only to UMC; 
 
𝛽5 = adjusted mean difference comparing combined SMT and SSM to UMC. 
  
This model considers each treatment group separately using an indicator of SMT only (SMT-
Only), an indicator of SSM only (SSM-Only), and an indicator of combined therapy with both 
SMT and SSM (SMT-and-SSM). We will also add the baseline outcome as a covariate to perform 
a variation of ANCOVA for repeated measures.  

 
 
PACBACK Protocol V8 page 67 
      
 
Our primary analysis will test the 
global hypothesis that these three 
treatment comparisons are all null 
using a multivariate Wald test with 3 
degrees of freedom and alpha=0.05/2 
to account for the pair of primary 
outcomes (pain and disability). We 
will then provide individual 
confidence intervals for each 
coefficient that compares an 
intervention group to medical care 
based on Fishers least significant 
difference methods which provide 
individual nominal 95% confidence 
intervals and also estimates the simultaneous coverage probability. 
 
A secondary evaluation will consider whether the separate effects of SMT and SSM are 
potentially additive, and this will be done using a formal test for interaction:  
 
Interaction Model:  
E( Yij  | Xij ) = 𝛽0 +   𝛽1 ⋅ Site(2)j +  𝛽2 ⋅ RiskGroupij + 
𝛽3⋅ SMTij + 𝛽4 ⋅ SSMij + 𝛽5 ⋅ SMTij ⋅ SSMij +  
𝛽6 ⋅ Period(2)ij + 𝛽7 ⋅ Period(3)ij 
    
In this model a test of H0: β5=0 allows us to determine if there is strong evidence for synergistic 
or antagonistic effects associated with combined treatment. Given that we evaluate interaction 
for both disability and pain we will use a Bonferroni corrected alpha of 0.05/2. 
 
Power and Sample Size for primary effectiveness outcomes # 2 and # 3: See Table 9.2. We will 
conduct longitudinal analysis of the underlying RMDQ and Pain NRS scores. Specifically, we 
will conduct analyses using the mean area under the curve for both disability and pain and use 
linear regression to evaluate treatment effects on the native underlying scales. With n=1000 
subjects evaluated through one year and using alpha=0.05/2 for the two outcomes and an overall 
F-test we have >80% power across a range of scenarios presented in the table below.  To orient 
standardized effects a marginal 2-point mean difference on RMDQ for any treatment modality 
compared to UMC assuming a standard deviation of 6.5 or less,149 153 corresponds to a Cohen’s 
D of 2.0/6.5 = 0.31, and >80% power to detect a marginal 1-point difference on Pain NRS 
assuming a standard deviation of 3.0 or less corresponds to a standardized effect of 0.33.149 153 
Note that our outcome is the area under the curve through 12 months, which is a patient-level 
weighted average, and the standard deviation (SD) for this outcome will be less than the SD for a 
single measurement. Our power calculations are conservative since we use the SD for a single 
measurement. Although we have <80% power if SMT and SSM have small marginal effects of 
0.25 SD and no additional benefit when combined (sub-additive 3 below) this scenario leads to 
no single treatment arm yielding an effect of 2 points on RMDQ (0.31 SD) or 1 point on Pain 
NRS (0.33 SD) and therefore suggests our design is appropriate for important and plausible 
effect sizes and not overpowered for effects that may not be meaningful. 
Table 9.2: Power for the overall F-test of equality of means under 
various alternative scenarios.  
Average pain intensity & disability over 12 months post-
randomization (alpha = 0.05/2) 
Alternative 
SMT 
Alone 
SSM 
Alone 
SMT 
+ 
SSM 
Power 
Additive 
0.20 
0.20 
0.40 
88% 
Sub-Additive 1 
0.25 
0.25 
0.35 
85% 
Sub-Additive 2 
0.30 
0.30 
0.30 
89% 
Sub-Additive 3 
0.25 
0.25 
0.25 
74% 
Single effect 1a 
0 
0.30 
0.30 
96% 
Single effect 1b 
0.30 
0 
0.30 
88% 
Single effect 2a 
0 
0.25 
0.25 
83% 
Single effect 2b 
0.25 
0 
0.25 
71% 

 
 
PACBACK Protocol V8 page 68 
      
 
Furthermore, we have excellent power to detect interaction effects where the effect of SMT and 
SSM may be synergistic or antagonistic, and using alpha=0.05/2 we have >80% to detect a 2.7-
point difference in disability or 1.3-point difference in pain treatment effects of one modality 
across the strata defined by the other treatment modality. 
 
Secondary Analyses of the 3 primary effectiveness outcomes and other secondary 
outcomes: We will conduct a number of pre-specified secondary analyses.  
 
Subgroup/Moderator Analyses: We will consider two pre-specified subgroup analyses to look at 
treatment effects within: subjects who are medium risk based on STarT Back, and subjects who 
are high risk; and subjects stratified based on their duration of LBP. Subgroup analyses will use 
logistic or linear regression among restricted subsets to quantify specific treatment effects, and 
formal evaluation of differences in treatment effects across subgroups will be conducted using 
treatment by subgroup interactions. In addition to the pre-specified subgroup analyses we will 
also conduct exploratory analyses to evaluate the heterogeneity of treatment effects according to 
Gender, Race, and Ethnicity. 
 
Responder Analysis: We will focus on evaluation of a >50% improvement in pain or function 
from baseline to six months, and from baseline to one year. We will also consider a >30% 
improvement, and a comprehensive responder analysis that looks at the cumulative percentage of 
subject achieving a range of improvement percentages as described in Farrar, Dworkin, and 
Max.76  
 
Secondary Outcomes: We will assess secondary outcomes including the PROMIS-29 measure, 
productivity loss, healthcare utilization (e.g., opioid use, injection, MRIs), and AEs for the 
combined group (SMT+SSM) and each intervention alone relative to MC. We will use linear or 
logistic regression and the Four Group model structure given above and will use linear mixed 
models or generalized estimating equations (GEE) for longitudinal analysis of secondary 
outcomes.154  
 
Time-until-recovery: An important class of secondary analyses will consider the time-until-
recovery based on measurements taken every 4 weeks during the year of follow-up. Specifically, 
we can define the time-until-recovery as the assessment month in which the subject is first 
observed to achieve an NRS=0 and RMDQ <= 2. We will use discrete time (monthly data) 
cumulative incidence curves to show the percent of subjects in each treatment group who have 
achieved a first recovery by each follow-up time period. We recognize that recovery may not be 
maintained, and subjects may subsequently relapse so we will also display plots showing the 
percent of subjects who are currently in the recovered state as a function of time. Formal 
comparison of cumulative incidence curves can be obtained using the log rank test since in this 
situation the cumulative incidence is simply 1-survival as would be computed using Kaplan-
Meier curves. In addition, we will use a model-based survival analysis.  
 
Cross-sectional outcomes at 2, 6, and 12 months: We will also conduct analysis of change in pain 
NRS, RMDQ, and STarT Back status from baseline. Satisfaction will also be analyzed at these 

 
 
PACBACK Protocol V8 page 69 
      
time points. This analysis will evaluate the magnitude of short, medium, and long-term effects of 
treatment, which are traditionally used in systematic reviews and meta-analyses. 
 
Mediation Analysis for Psychosocial Factors: Formal mediation analysis 155-157 will focus on 
characterizing the degree to which self-efficacy, coping, kinesiophobia, and pain catastrophizing 
measured at 8 weeks can explain treatment effects at 6 months, and whether these measures 
obtained at 6 months explain long-term treatment effects (1 year). We will quantify the percent 
of the treatment effect that is explained by changes in each scale individually, and in totality 
when included in a multivariate model for the outcome.158 We will analyze mediation for cLBP, 
recovery at six months and change in pain NRS and RMDQ measured at 6 months and 1 year.  
 
Longitudinal analyses of patient trajectories for pain and disability: We will use the monthly 
measures of disability and weekly measures of pain to conduct longitudinal analysis that 
characterizes the mean profile over time for each intervention group. Formal comparison of 
profiles will be based on linear mixed models or GEE. Furthermore, we will conduct exploratory 
analyses that assume latent classes with associated trajectories, and we can evaluate whether 
these groups differ across the intervention arms.159 We have recently used these methods for 
analysis of the BOLD back pain cohort.160  
 
Longitudinal Analysis Adjusting for Concomitant/Subsequent Therapy: Our first analysis will be 
a descriptive summary of the types and frequency of additional treatments received throughout 
the study. The initial study intervention occurs within the first two months and outcomes are 
collected through one year. Therefore, there is potential for variation in the treatment received 
according to randomized group or non-study interventions during months 3-12. Intermediate 
treatment received is a post-randomization variable and potential intermediate outcome that will 
be considered in mediation analysis. In addition, we can use structural nested mean models 
(SNMMs) or marginal structural models 161 162 to adjust for time-varying confounding (treatment 
contamination) associated with intermediate treatment received. For example, if we consider 
longitudinal concomitant treatment ak, measured at times k=1, 2, …, m, then using SNMM 
notation we can define the 1-year counterfactual outcome for subject i as Yi(Z, a1, a2, …, am) 
which represents the potential outcome associated with baseline treatment Z and time-varying 
concomitant treatments. We can use either SNMMs or MSMs to estimate population mean 
outcomes under controlled concomitant treatment paths such as the expected outcome with 
treatment Z and no additional longitudinal treatments: mean of Yi(Z, 0, 0, …, 0). For these 
longitudinal analyses we will use the monthly measured RMDQ and Pain NRS as the outcomes 
in parallel regression analyses. We have previously conducted critical evaluation of such 
methods for the analysis of surgical non-compliance.163 
 
Impact of cLBP & recovery definitions: The robustness of NIH RTF case definition of cLBP will 
be assessed using measures of pain frequency and LBP-related burden (pain, disability, 
productivity loss, healthcare utilization) by assessing differences between subjects meeting the 
case definition and those who do not. We will also explore the clinical and demographic 
characteristics of subjects with high LBP-related burden who fail to meet the case definition for 
cLBP in addition to the characteristics of subjects with low LBP-related burden who meet the 
case definition for cLBP. We will also assess the impact of an alternative definition of recovery 
(e.g., NRS <2 and RMDQ <3) on treatment effects at 6 and 12 months. 

 
 
PACBACK Protocol V8 page 70 
      
 
Sample Size for Seconday Objective of Implementation: Qualitative data collection associated 
with Aim 2 will require a minimum of 22-30 participants from each of the patient, facility, and 
organizational levels; this is the approximate number to reach ‘saturation’, or the point where no 
new themes emerge.164 165 
 
Analysis plan for Implementation: Qualitative and quantitative analyses will be performed for 
data collected regarding contextual information that will inform future implementation and 
results interpretation, as described in Section 6.2.6. Qualitative data will be analyzed using 
template style qualitative content analysis using NVivo qualitative software or similar. Data 
collection and analyses will be performed by clinical site investigators and designees 
experienced in analysis of qualitative data using methods applied previously.166-169 All qualitative 
analyses will begin with the creation of a working codebook, developed by reviewing samples of 
texts to gain a general understanding of the data and establish preliminary codes.164 165 168 
Representative quotations will be identified during the coding process; coded themes will be 
grouped into larger thematic categories. Themes will then be quantified by categorizing them as 
present or absent for each case, and presented as frequencies.164 The DCC will oversee the 
conduct of validity checks of 10% of the analyzed cases to ensure consistency with the 
codebook. Quantitative analyses will be performed by the DCC and will include descriptive 
statistics data collected as described in Section 6.2.6. Independent t-tests (for means) and z-tests 
(for proportions) will be used to assess group differences when appropriate. 
 
General Missing Data Considerations: 
Missing data may include missing covariate information, study dropout, or missed and/or 
mistimed participant visits. While the PACBACK protocol includes procedures to ensure the 
most “complete” follow-up data on every enrolled participant, it is likely that some participants 
will have incomplete data. We will determine reasons for missingness, classifying each 
missingness pattern as missing completely at random (MCAR), missing at random (MAR), or 
missing not at random (MNAR). The MCAR mechanism occurs when the probability of 
response is independent of both the observed data and the unobserved data170. All protocols will 
include recommended sensitivity analyses that will help determine the extent of potential biases 
that could affect the results. 
 
In longitudinal analyses, likelihood-based analyses of complete-case data for the linear mixed-
effects model, the generalized linear mixed-effects model, and the nonlinear mixed-effects model 
lead to valid inference under MCAR and MAR mechanisms, whereas the GEE analyses lead to 
valid inference only in the presence of MCAR mechanisms.170 171 Statistical tests to assess the 
validity of the MCAR assumption in certain circumstances are available, but they are model-
dependent and non-robust.172-174 In general, we will advocate the use of multiple imputation 
(MI)175 both to assess the sensitivity of results and to correct for bias from missing covariates. 
We will consider the missing data mechanism, analysis approach, and plausibility of the 
congeniality assumption.176 177 If MNAR data are suspected, there are three basic approaches to 
address this challenge, namely, (1) selection models178-180, (2) pattern-mixture models181 182 and 
(3) MI.175 183 We recommend MI because it appears to be more robust. We can apply MI using 
weights dependent on the probability of dropout to assess the dependence of results on dropout. 

 
 
PACBACK Protocol V8 page 71 
      
We will also consider selection models with varying dropout parameters in sensitivity 
analyses.183 184 
 
Potential Problems & Alternative Strategies: 
Factorial Model Assumptions: We have assumed both an additive data-generating model with 
small effects and alternative sub-additive scenarios with moderate effects for the three primary 
effectiveness outcomes.  However, for the secondary binary outcomes and we have assumed 
additivity to assess power for SMT and SSM treatment main effects.  For these binary outcomes 
it is possible that there is an interaction that is either synergistic or antagonistic (sub-additive). In 
this situation our proposed analysis will estimate an average treatment effect rather than a 
common treatment effect. A synergistic interaction however would suggest that SMT + SSM 
produce greater effects together, than when used alone. Conversely, an antagonistic interaction 
would suggest that their effects are less than additive. Both scenarios would provide new and 
important information and advance what is known about these therapies and how they should be 
applied for acute and sub-acute LBP. Importantly, even if an interaction is observed, we have 
>80% power to detect the following differences between the combined group or either of the 
single interventions alone compared to medical care: For prevention of chronicity, we will be 
powered to detect a reduction of 9% (RR=0.55) at an event rate of 20% in the MC group, a 
reduction of 11% (RR=0.63) if the event rate is 30%, and a reduction of 12% (RR=0.7) if the 
event rate is 40%. For recovery, we will be powered to detect an increase of 7% (RR=2.4) at an 
event rate of 5% in the MC group, 9% (RR=1.9) if the event rate is 10%, and 10% (RR=1.67) if 
the event rate is 15%.  
 
10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1 
Data Collection Forms  
Initial screening data will be directly entered by potential study participants via a web-based survey 
supplied by the DCC. Phone-based screening data and in-person/video-conference screening data 
obtained at the in-person/videoconference visit will be entered directly into the study portal by research 
staff at the sites to confirm study eligibility. For consented participants, protected health and contact 
information will be stored in a separate limited-access REDCap database and no research personnel will 
have data export rights in this database. Data collected as a part of the research study protocol database 
will be stored in a completely separate database, linked by study ID. A procedure/visit case report form 
will be filled out by research staff for every study-related visit and electronically entered directly into the 
web-based portal. Electronic web-based surveys will be sent to study participants on a monthly basis, 
with computer-assisted telephone interviewing or mailed surveys as a parsimoniously used back-up in 
cases where follow-up may be challenging. Printable CRFs will be made available for every study 
assessment. 
10.2 
Data Management  
Data management in the LBP project will be almost exclusively web-based. The UWA DCC will support 
an https-secured web page (www.PACBACK.ORG) that provides a centralized location for public 
information about the project for potential subjects, investigators, and institutional agencies. The web 
page will contain a link to the project portal. Study personnel will log on to the private portal on the study 
web page with individual Shibboleth-based user names and passwords to securely perform study data 
management activities. Shibboleth is a standards-based, open source software package for web single 

 
 
PACBACK Protocol V8 page 72 
      
sign-on across or within organizational boundaries. An overview of the DCC responsibilities and data 
management system is presented below. 
 
 
 
Study Integration: The UWA DCC team has extensive experience developing Application Programming 
Interfaces (APIs), which allow multiple software programs to seamlessly interact and communicate with 
one another in a simple and intuitive interface. The web portal API will serve as the wrapper for all data 
management tools and software utilized in the LBP project, including: study ID assignment, screening, 
centralized image storage (if needed), prospective data collection forms and surveys, and study operations 
reporting. Screening and eligibility will be determined centrally through the portal and all subjects 
screened under the LBP trial protocol will be assigned a sequentially generated study participant ID. The 
DCC will maintain an additional REDCap database to centrally and securely store identifiable patient 
information, separating patient contact information from research study data. For each REDCap database, 
the DCC will use distinct data access groups for clinical recruitment sites. 
 
Electronic Data Capture: The UWA DCC supports its own installation of REDCap, which is software 
specifically designed for electronic data capture that we have used successfully in several multi-site 
clinical trials. REDCap features include differentiated user roles and privileges, password and user 
authentication security, electronic signatures, SSL encryption, and comprehensive auditing to record and 
monitor access and data changes (http://www.project-redcap.org/software.php). REDCap will serve as the 
architectural backbone for all data captured prospectively in this study, with all data linked by study 
subject ID. The web-based data management portal allows for four participant contact methods: research 
coordinator data entry; electronic survey; computer-assisted telephone interviewing (CATI); or Short 
Message Service (SMS) text message. All survey modalities are customized to incorporate project logos 
and information to increase participant recognition and response rate. Furthermore, surveys may be 

 
 
PACBACK Protocol V8 page 73 
      
distributed on any time schedule (e.g., monthly for pain and disability), and in any designated survey 
format. 
 
Access and Security: The DCC will invite each research staff member at the clinical recruitment sites to 
obtain a University of Washington NetID, which will be required to gain access to the secured study for 
screening, randomization, and data entry. Research staff will be grouped into data access groups whereby 
study participant data will be separated by site, as appropriate. The clinical recruitment sites are 
responsible for scheduling patient follow-up visits. REDCap databases are stored on a secure electronic 
server with username and passwords login for individual users and will be backed up nightly The 
REDCap servers are virtual machines (VMs) located on UW DCC hardware in a secure server room. Our 
server room meets the technical requirements for HIPAA compliance and hosts servers that do contain 
PHI. Storage for all study data is backed by (2) dedicated Network Appliance FAS2050 storage 
appliances. The filer provides highly fault tolerant storage using large RAID volumes, on-line hot-spare 
drives, and built-in, proprietary 'snapshot' file system technology that automatically creates hourly, daily, 
and weekly on-line backups of modified files. 
10.3 
Quality Assurance  
10.3.1 Training 
Training: Before any clinical recruitment site may begin recruitment for this study, the DCC will provide 
two training sessions on the data management system for all research staff. The first training session will 
be a GoToMeeting virtual tour of the data system conducted by the DCC protocol operations specialist; 
the second training is a GoToMeeting virtual training session where research staff are observed 
interacting with the system by a UWA DCC staff member and are required to demonstrate proficiency in 
key data management steps (screening, randomization, data entry, documentation of AEs, data 
management protocol compliance, etc.). As with most studies, there will likely be turnover in recruitment 
site personnel necessitating a process for ongoing training. The DCC will create data management system 
training videos that covers the material of the first training session. All new research staff will be required 
to view the suite of training videos and then complete a second virtual training session with the DCC 
protocol operations specialist prior to being given a log-in and access to the study portal. 
Detailed communication about protocol and case report forms changes will come through the DCC 
through Basecamp (www.basecamp.com) notifications, a program used to facilitate project management 
and study-wide communication. The DCC will additionally develop a question-by-question (QxQ) 
document that outlines in detail the intent of each research staff-facing CRF question and response. 
 
10.3.2 Quality Control Committee  
Missing data reporting and other customized reports will be developed by the DCC in collaboration with 
the CCC and recruitment team in order to facilitate efficient work-flow and high-quality data capture. A 
subset of key personnel from the DCC and CCC will serve as an operations committee and review quality 
control reports on a weekly or biweekly basis, though quality control reports will be made available on a 
daily basis. CRF-specific follow-up rates will be tabulated on a nightly basis and reviewed during the 
weekly check-in meeting with each clinical recruitment site. Nightly, the DCC will generate graphs that 
monitor CRF-specific follow-up rates over time as well as data quality trigger rates over time to 
prospectively monitor potential issues that may develop gradually or acutely over time. A data query 
resolution dashboard will be available to each site on a continuous basis. In similar studies, we have 
found that establishing a fixed-day for a monthly review of all unresolved queries is an adequate balance 
of time to resolution and alert fatigue. 
 

 
 
PACBACK Protocol V8 page 74 
      
10.3.3 Metrics 
For each monthly follow-up survey, we aim to achieve an 85% or higher follow-up rate. We will utilize a 
combination of web-based survey, telephone and text-based outreach, and mailed surveys to achieve 
maximal survey response – especially at the 6 and 12-month follow-up time points. Survey completion 
rates will be primarily based upon the completion of pain and functional outcome measures, but the DCC 
will additionally tabulate follow-up by each instrument to monitor and evaluate survey burden. 
 
Loss to Follow-Up: Participants are considered loss to follow-up if a participant 
 
1. Dies, or they 
2. Missed 3 consecutive monthly surveys, and 
3. Missed 4 consecutive weekly surveys (~ 1 consecutive month), and  
4. 3 email/text auto or manual reminders and 3 phone calls result in no response from the participant 
 
When criteria 2-4 are met, the DCC will stop (turn off) the weekly and monthly surveys with the 
exception of the 6 and 12 month surveys (primary outcome). Study staff will contact participants prior to 
request they provide data at these time points.  
 
Participants’ status may be adjusted if the participant contacts the study and begins participating in data 
collection activities. 
 
 
10.3.4 Protocol Deviations 
Study deviations and violations will be tracked prospectively at the participant-level on an ongoing basis 
in the study portal, and will be reviewed during the annual in-person site monitoring visit. During in-
person monitoring visits, every study participant will be 100% monitored for the presence and absence of 
a priori defined protocol violations. 
 
10.3.5 Monitoring 
On the portal Reports page, missing data and data quality reports are provided by the DCC on a nightly 
basis and reviewed weekly by the DCC protocol operations specialist. Free text data collection from study 
participants will be minimized to the extent possible and field masking and automated out of range checks 
will be implemented where applicable. 
 
For ongoing data querying and cleaning, the DCC will implement and utilize a query resolution 
dashboard where the protocol operations specialist will visually review 100% of all data entered in the 
previous week and provide documentation that each participant-CRF has been reviewed. On a nightly 
basis, the DCC will also generate a comprehensive data quality report to flag unusual data and will be 
made broadly available to the study team. The protocol operations specialist will flag any data that trigger 
a review through logic-based checks, visual checks, or intermittent missing data. Research staff at the 
recruitment sites will be asked to review each outstanding query and respond with “confirmed” or 
“corrected” and may provide a comment beside each query to note relevant details. Each query will be 
closed by the DCC protocol operations specialist. 
 
During annual site monitoring visits to the clinical recruitment sites, the DCC will conduct 100% 
monitoring of in-person/videoconference screening data, informed consent documentation, and fidelity 
with the portal-assigned randomized treatment. In addition to the previously described study-wide data 
quality reports, the DCC will generate a compact report for each study participant enrolled in the study on 

 
 
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a nightly basis. This report will be made broadly available and will serve as the basis for in-person 
monitoring. 
 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 
Institutional Review Board (IRB) Review  
This protocol, the informed consent document, CRFs, and any subsequent modifications will be reviewed 
and approved by the IRB responsible for oversight of the study.  
11.2 
Informed Consent Forms 
PIs or designees (research staff) will conduct the informed consent process.  
 
Prior to the baseline appointment, participants will be given a copy of the consent form to review on their 
own, with ample time. The consent form will provide information regarding the study purpose and 
research design, procedures, potential risks and benefits, alternatives to participation, voluntary nature of 
participation, compensation, privacy and confidentiality, research-related injury, and disclosure of new 
information regarding participation. Contact information for the PIs and study coordinators will also be 
provided. Research staff will meet one-on-one with the participant in a private space (via HIPAA secure 
videoconference or in-person) and review each section of the form. Informational materials will be used 
to facilitate understanding. Participants will be invited to ask questions section by section. Only 
individuals who demonstrate comprehension will be considered eligible to participate. Persons who are 
not able to read and write in English or consent for themselves are ineligible.  
 
A signed consent form (e-Consent or written) will be obtained from each participant. All participants will 
receive a copy of the signed form for their personal records. Original written signed consent forms will be 
secured in the participant’s research file at each of the respective clinical coordinating centers. E-Consent 
forms will be secured in REDCap. Consent forms for all enrolled participants will also be sent to the DCC 
electronically via the HIPAA compliant study portal.  
 
Changes to the consent form may be initiated by research staff, investigators, or regulatory oversight 
boards as needed. Any changes will be approved by the Principal Investigators at each of the Clinical 
Coordinating Centers and submitted to the IRB of record for approval.  
 
11.3 
Participant Confidentiality  
Procedures are in place for maintaining the full confidentiality of all information collected. All staff 
receive HIPAA and data safety training. Participant confidentiality will be safeguarded by the use of 
password protected databases and locked file cabinets. Research records will be stripped of all identifying 
information, with keys identifying individual subjects available only to the PIs and selected designees. 
Further, access to identifiable private information from study participants will only be accessible to study 
related personnel who have met the training requirements for the responsible conduct of research, HIPAA 
and data security and have completed study specific training. The HIPAA compliant Zoom 
videoconferencing software will be used at both CCCs.   
 
Any data, forms, reports, and other records that leave the clinical sites will be identified only by a 
participant identification number to maintain confidentiality. Data are managed by study number and 
analyzed anonymously. All published reports will be of summary nature and no individual subjects will 

 
 
PACBACK Protocol V8 page 76 
      
be identified beyond the investigative staff involved. Responses to online surveys are encrypted during 
transmission to the study center and there is no outbound transmission of identifying information from 
study servers to study participants. 
 
Information will not be released without written permission of the participant, except as necessary for 
monitoring by the IRB, the NCCIH, the OHRP, or other regulatory oversight agencies.  
 
To further protect participant privacy, we have obtained a Certificate of Confidentiality from the National 
Institutes of Health. The researchers can use this Certificate to legally refuse to disclose information that 
may identify participants in any federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist 
any demands for information that would identify participants, except as explained below. 
 
The Certificate cannot be used to resist a demand for information from personnel of the United States 
Government that is used for auditing or evaluation of federally funded projects. 
 
A Certificate of Confidentiality does not prevent participants from voluntarily releasing information about 
themselves or their  involvement in this research. If an insurer, employer, or other person obtains written 
consent to receive research information, then the researchers may not use the Certificate to withhold that 
information. 
 
If the investigators learn that a participant or someone with whom they are involved is in serious danger 
or potential harm, they will need to inform, if required by state law, the appropriate agencies. 
 
11.4 
Study Discontinuation  
The study may be discontinued at any time by the IRB, the NCCIH, the OHRP, or other government 
agencies as part of their duties to ensure that research participants are protected.  
12. COMMITTEES 
Data Safety and Monitoring Board 
Appointed by NCCIH, the DSMB plays a crucial role in ensuring the safety and welfare of patients 
enrolled in this trial, and operates without undue influence from any interested party, including 
PACBACK study investigators or NCCIH staff. DSMB responsibilities include protocol approval, interim 
review of trial enrollment, protocol compliance, and safety data. The protocol review committee is a 
subset of the DSMB.  
 
PACBACK Steering Committee 
The Steering Committee will assume responsibility for the overall direction of this study which includes 
design and conduct of the study; preparation of essential study documents (e.g., study protocol, protocol 
amendments, and data collection forms); monitoring recruitment and retention of study participants; 
changes in study procedures as appropriate; review of study progress in achieving study goals/milestones; 
review and implementation of recommendations from the DSMB; review and respond to other general 
advice and/or recommendations (e.g., from the NCCIH program officer and the PIs). The committee will 
make recommendations via email correspondence. If requested by a majority of members, or by NCCIH 
or the CCC and DCC PIs,  the committee will meet in-person or remotely. This committee includes the 
following members, and 7 persons constitute a quorum. 
 
Dr. Wendy Weber, Project Scientist, NCCIH 

 
 
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Dr. Gert Bronfort, CCC PI, University of Minnesota 
Dr. Roger Chou, Co-Investigator, Oregon Health Sciences University 
Dr. Anthony Delitto, CCC Co-PI, University of Pittsburgh 
Dr. Roni Evans, CCC Co-Investigator, University of Minnesota 
Dr. Steven George, Co-Investigator, Duke University 
Dr. Carol Greco, Co-Investigator, University of Pittsburgh 
Dr. Patrick Heagerty, DCC PI, University of Washington 
Dr. Francis Keefe, PhD, Co-Investigator, Duke University  
Dr. John Licciardone, Co-Investigator, University of North Texas 
Dr. Michael Schneider, CCC Co-PI, University of Pittsburgh 
Dr. Dennis Turk, Co-Investigator, University of Washington 
Dr. Peter Murray, Program Officer, (NCCIH ex officio member)  
  
PACBACK Clinical Coordination Committee (Operations) 
The clinical coordination committee is responsible for the implementation of the protocol at each of the 
coordinating sites. This includes the CCC & DCC PIs, CCC Co-Investigators, project coordinators, and 
the NCCIH project scientist. 
 
PACBACK Coordination Team  
The PACBACK Coordination team includes the PIs, Co-Is, Research Coordinators, and other local 
research staff (e.g., site leads, recruitment coordinators) at each of the UMN and UPITT CCCs. This team 
is responsible for coordinating study activities between and within the CCCs, and with the DCC, to 
ensure consistency in protocol implementation; this will include staff training, patient enrollment, 
intervention delivery and fidelity monitoring, and data collection. 
 
PACBACK Study Monitoring Committee 
This committee performs regular onsite and virtual monitoring of individual eligibility determination, 
assesses adherence to the protocol, ensures the ongoing implementation of appropriate data entry and 
quality control procedures, and in general assesses adherence to good clinical practices.  
 
PACBACK Advisory Committee 
This committee includes patient, provider, health system leadership, and payer stakeholder representation 
and will provide guidance and advice to the Steering Committee regarding recruitment, communication 
and dissemination and implementation related efforts. 
 
Publications, Presentations and Ancillary Studies (PPAS) Committee 
This committee will facilitate timely dissemination of study findings, maintain high scientific standards 
for published material, prioritize the order of publication and presentations, and ensure equitable 
investigator participation and attribution of authorship. The committee will ensure publications are well-
aligned with the trial’s research agenda and are not redundant. The PPAS committee will review all 
proposals for data analysis, as well as research abstracts, presentations, and manuscripts before 
submission. The committee will also review proposals for ancillary studies. The committee will ensure 
that each publication that meets NIH Open Access criteria is deposited in PubMed Central.  See section 
13. Publication of Research Findings for additional information.   
  
13. PUBLICATION OF RESEARCH FINDINGS  
The DCC is responsible for setting up systems with the PPAS which is a subset of the Steering 
Committee to develop publication guidelines that include procedures for reviewing and tracking 

 
 
PACBACK Protocol V8 page 78 
      
publications and presentations. The study Publications Guidelines document details processes for defining 
study publications, for assigning authors in accordance with the guidelines of the International Committee 
of Medical Journal Editors, and for reviewing publications prior to submission. The study website will 
include a searchable list of all analysis proposals and will track their status toward publication. The DCC 
will conduct all multi-site analyses for the primary publications and presentations. 
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15. SUPPLEMENTS/APPENDICES 
Study Accrual and Retention Plan 
Data Safety Monitoring Plan