SMART Stepped Care Management for Low Back Pain in the Military Health System
Phase: NA
Conditions: Low Back Pain, Chronic Pain, Military Personnel, Veterans
Sponsor: Brooke Army Medical Center

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Clinical Intervention Study 
Protocol 
 

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TABLE OF CONTENTS 
Page 
Clinical Intervention Study Protocol ........................................................................................... 1 
TABLE OF CONTENTS .............................................................................................................. 2 
SMART Stepped Care Management for Low Back Pain in Military Health System .................. 5 
Tool Revision History: ................................................................................................................ 6 
STUDY TEAM ROSTER ......................................................................................................... 10 
PRÉCIS .................................................................................................................................... 12 
1. STUDY OBJECTIVES ........................................................................................................... 13 
1.1 Primary Objectives ............................................................................................................ 13 
1.2 Secondary Objectives ........................................................................................................ 14 
2. BACKGROUND AND RATIONALE ................................................................................... 14 
2.1 Background on Condition, Disease, or Other Primary Study Focus ................................. 14 
2.2 Study Rationale .................................................................................................................. 15 
3.  STUDY DESIGN .................................................................................................................... 16 
4.  SELECTION AND ENROLLMENT OF PARTICIPANTS .............................................. 16 
4.1 Inclusion Criteria ............................................................................................................... 16 
4.2 Exclusion Criteria .............................................................................................................. 16 
4.3 Study Enrollment Procedures ............................................................................................ 17 
5.1 Interventions, Administration, and Duration ..................................................................... 18 
5.1.1  Physical Therapy ........................................................................................................... 18 
5.1.2 Move to Health (M2H) ................................................................................................. 19 
5.1.3  PT+M2H ........................................................................................................................ 19 
5.1.4  Mindfulness ................................................................................................................... 19 
5.2   Handling of Study Interventions ........................................................................................ 20 
5.3   Concomitant Interventions ................................................................................................ 20 
5.3.1   Allowed Interventions .................................................................................................. 20 
5.3.2   Prohibited Interventions ............................................................................................... 20 
5.4 Adherence Assessment ...................................................................................................... 21 
5.5    Considerations for Future Implementation ....................................................................... 21 
6. STUDY PROCEDURES ......................................................................................................... 22 
6.1 Schedule of Evaluations .................................................................................................... 22 

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6.2 Description of Evaluations ................................................................................................ 22 
6.2.1   Screening Evaluation .................................................................................................... 22 
6.2.2   Enrollment, Baseline, and/or Randomization ............................................................... 23 
6.2.3   Blinding ........................................................................................................................ 25 
6.2.4   Follow-up Visits ........................................................................................................... 26 
6.2.5   Completion/Final Evaluation ........................................................................................ 26 
7. SAFETY ASSESSMENTS ...................................................................................................... 27 
7.1 Specification of Safety Parameters .................................................................................... 27 
7.2 Methods and Timing for Assessing, Recording and Analyzing Safety Parameters .......... 27 
7.3 Adverse Events and Serious Adverse Events .................................................................... 27 
Definitions ................................................................................................................................. 27 
Adverse Event (AE) ................................................................................................................. 27 
Unanticipated Problems (UP) .................................................................................................. 27 
Serious Adverse Event (SAE) ................................................................................................. 28 
7.4 Reporting Procedures ........................................................................................................ 28 
Characteristics of an Adverse Event .......................................................................................... 28 
Relationship to Study Intervention .......................................................................................... 28 
Expectedness of SAEs ............................................................................................................. 28 
Severity of Event ..................................................................................................................... 28 
7.5 Follow-up for Adverse Events ........................................................................................... 29 
7.6 Safety Monitoring .............................................................................................................. 29 
8.   INTERVENTION DISCONTINUATION .......................................................................... 29 
9.  STATISTICAL CONSIDERATIONS .................................................................................. 29 
9.1 General Design Issues ....................................................................................................... 29 
9.2 Sample Size and Randomization ....................................................................................... 30 
9.3  Definition of Populations ................................................................................................... 34 
9.4 Interim Analyses and Stopping Rules ............................................................................... 34 
9.5 Outcomes ........................................................................................................................... 35 
9.5.1   Primary and Secondary Outcomes ............................................................................... 35 
Additional Exploratory Outcomes and Assessments ................................................................. 35 
9.6 Data Analyses .................................................................................................................... 36 
10. DATA COLLECTION AND QUALITY ASSURANCE ................................................... 39 
10.1 Data Collection Forms ....................................................................................................... 39 
10.2 Data Management .............................................................................................................. 40 

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10.3 Quality Assurance .............................................................................................................. 40 
10.3.1   Training ...................................................................................................................... 40 
10.3.2   Quality Control Committee ........................................................................................ 41 
10.3.3   Metrics ........................................................................................................................ 41 
10.3.4   Protocol Deviations .................................................................................................... 41 
10.3.5   Monitoring .................................................................................................................. 41 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY .................................................... 42 
11.1 Institutional Review Board (IRB) Review ........................................................................ 42 
11.2 Informed Consent Forms ................................................................................................... 42 
11.3 Participant Confidentiality ................................................................................................. 42 
11.4 Study Discontinuation ....................................................................................................... 42 
12. COMMITTEES ..................................................................................................................... 42 
13.  COVID-19 STUDY IMPACT .............................................................................................. 44 
13.1  Timeline of COVID-19 Impact and Activities ................................................................. 44 
13.2  Data Management Considerations in Response to COVID-19 Disruptions ..................... 44 
APPENDICES 
I. 
Literature Cited 
II. Manual of Operations 
III. Informed Consent Forms 
IV. Case Report Forms (adverse events, serious adverse events, informed consent checklist, 
study completion form, randomization and enrollment, eligibility screening checklist) 
 V.  Responses to NCCIH OCRA and PMC Study Design Work Group regarding study 
design and biostatistics 

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SMART Stepped Care Management for Low Back 
Pain in Military Health System 
 
Study Chair or Principal Investigator:   
Julie M. Fritz, PhD, PT, FAPTA, Distinguished Professor, Department of Physical 
Therapy & Athletic Training, University of Utah 
Dan Rhon, DSc, PT,PhD, Department of Rehabilitation Medicine, Brooke Army 
Medical Center 
 
 
 
Supported By: 
 
The National Center for Complementary and Integrative Health, NIH-DoD-VA 
Pain Management Collaboratory - Pragmatic Clinical Trials 
Demonstration Projects 
Grant Number:  1UH3AT009763-01 
 

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Tool Revision History: 
Version Number: 1.0 
Version Date: May 18, 2018 
Summary of Revisions Made: Original Version 
 
Version Number 1.1 
Version Date: December 18, 2018 
Summary of Revision Made:   
i) Appendix V added. Appendix V contains the document outlining responses to NCCIH OCRA and 
PMC Collaboratory Study Design Work Group comments and responses 
 
Version Number 2.0 
Version Date: February 20, 2019 
Summary of Revisions Made: 
i) 
Grant number changed from UG3 to UH3  
ii) 
List of participating sites was updated to include site PIs and Research Coordinators at each 
Military Treatment Facility at which the study will be conducted. 
iii) Added “chronic” to description of the LBP patient population in Objective section of the PRECIS 
and elsewhere in the Study Rationale and Safety Assessment Sections of the Protocol.  
iv) Corrected timeframes for assessments listed in sections 5.1 and 9.6 for consistency with the 
schedule of events which clarifies that follow-up assessments occur 8 and 18 weeks after 
enrollment. 
v) 
Section 4.1, eligibility criterion #5 clarified to reflect ability to attend 16 weeks of treatment 
without a planned absence of 2 weeks or more. 
vi) Sections 4.3, 9.2.2 - additional details of randomization procedures in RedCap are provided. 
vii) Section 5.2 – clarified that intervention dose will be based on the number of sessions attended. 
viii) Section 6.2.1.1, word “soldier” replaced with “participant” because active duty status is not 
required for participation. 
ix) Section 6.2.1.1 – typo corrected. Statement now reads “Individuals will be provided two copies...” 
x) 
Section 6.2.2.3, additional details for Phase I and Phase II randomization procedures are provided. 
Stratification variables at each randomization are clarified. 
xi) Section 6.2.3, clarified the blinding status of study statisticians 
xii) Section 7.2 – procedures for collecting AEs and SAEs were clarified. 
xiii) Section 7.4  - clarified reporting procedures for AEs and SAEs.  
xiv) Section 7.6 – clarifications of the DSMB procedures. Specified the specialty areas for DSMB 
members, persons who will attend closed meeting and the establishment of a charter document at 
the first DSMB meeting. 
xv) Section 9.2.1 – specified procedures for sensitivity analysis should missing data prove to be 
missing not at random 

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xvi) Sections 9.3 and 9.6 – clarification was added to state that intention-to-treat will guide analyses 
throughout the study. 
xvii) Section 9.6 – added clarification to data analysis for Aim II that Phase I treatment will be included 
as a covariate. 
xviii) Section 10.3.3 – added monthly reports of quality metrics to be generated by the Quality Control 
Committee for review by research team and site research staff. 
xix) Section 12 – added description of Project Steering Committee including membership, roles and 
responsibilities. 
Version Number 2.1 
Version Date: March 22, 2019 
Summary of Revision Made:   
i) Study Team Roster – updated contact information for COL Deydre Teyhen 
ii) Clarification made in PRECIS on stratification variables to be used in Phase I and Phase II 
randomizations. 
iii) Sections 4.3 and 9.2.2 – clarified that an independent statistician will develop random allocation 
tables for Phases I and II. 
iv) Section 6.1 – Schedule of Events: added the Start Back Screening Tool to the Baseline Evaluation 
v) Section 6.1 – Modified the time windows for completion of follow-up assessments 
vi) Section 6.2.3 – added the following statement: “An unblinded study statistician will prepare aspects 
of the Data Safety Monitoring Reports that provide unblinded information for closed session 
consideration until such time that the study database is closed and locked.” 
vii) Section 6.2.4 – updated the time windows for completion of follow-up assessments and clarified the 
mode for conducting each follow-up assessment as in-person or remotely via RedCap link. 
 
Version Number 2.2 
Version Date: May 21, 2019 
Summary of Revisions Made: 
i) Study Aim V modified to remove PTSD and post-concussive symptoms as sub-grouping variables. 
Baseline opioid use added to Specific Aim V as sub-grouping variable. Change made to PRECIS and 
sections 1.1 and 9.6. 
ii) Section 9.6 – clarified the operational definitions for sub-grouping variables 
iii) Section 5.4 – clarified the definitions of adherence by treatment group that may be used for a “per-
protocol” analysis. 
iv) Section 5.5 – this section was added to describe opportunities for future implementation of study 
findings as appropriate based on the results. 
 
Version Number 2.3 
Version Date: October 1, 2019 
Summary of Revisions Made: 
i) Section 4.2 – exclusion criteria: clarified that exclusion  criterion 5 excludes individuals with any 
spinal surgery, not exclusively lumbar spine surgery, in the past year. 

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ii) Section 4.2 – exclusion criteria: clarified exclusion criterion 6 by removing “retiring from active 
duty”. Exclusion criterion 6 now reads “Pending a medical evaluation board, discharge from the 
military for medical reasons, or pending or undergoing any litigation for an injury.   
iii) Section 6.1 we will also collect limited duty days as an exploratory outcome for the subset of 
participants who are active duty.  This data will be administratively collected at the conclusion of 
the participant’s study participation from the Military Operational Data System (MODS). This 
additional also noted in section 3 (Study Design); section 6.2.5 Completion/Final Evaluation; 9.1 
General Design and 9.5 Additional Exploratory Outcomes and Assessments . 
iv) Section 6.1 added collection of Perceived Readiness for Duty questions at baseline for active duty 
personnel only.  
v) Section 6.1 and 6.2.2.2 – added the Pain Body Diagram to the data collection instruments with 
explanation of the form in section 6.2.2.2. 
vi) Section 6.2.2.2 – the wording of the PASS questionnaire was updated for consistency with 
previously-published studies. 
 
Version 2.4 
Version Date: June 17, 2020 
  Summary of Revisions Made: 
i) Study Team Roster and Participating Sites: updated to reflect study personnel changes. 
ii) Section 6.1 – added two surveys recommended by the Pain Management Collaboratory for data 
harmonization. The COVID-19 impact survey was added to the baseline assessment. The 
Use of nonpharmacological and self-care approaches (NSCAP) was added to the 1-year 
assessment. 
iii) Section 13 – this section was added to document the impacts of COVID-19 on the study. Section 
13.1 provides a timeline of COVID-related disruptions. Section 13.2 provides a summary of 
COVID-related impacts of data management. 
 
Version 2.5 
Version Date: December 14, 2020 
  Summary of Revisions Made: 
i) Study Team Roster and Participating Sites: updated to reflect study personnel changes. Tripler 
Army Medical Center was added as a recruitment site. Fort Hood (Darnall Army Medical Center) 
was added as an inactive recruitment site. 
ii) Section 6.2.2.3 – the description of stratification of randomization by site was updated to reflect the 
addition of Tripler and inactive status of Darnall Army Medical Center 
iii) Section 9.2.2 -  the description of stratification of randomization by site was updated to reflect the 
addition of Tripler and inactive status of Darnall Army Medical Center 
 
 

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Version 3.0 
Version Date:    June 7, 2023 
Summary of Revision Made: 
i) Study Team Roster and Participating Sites: updated to reflect study personnel changes 
ii) PRECIS, sample size and population section – updated total sample size to 850 from original 
sample size of 1,200. 
iii) Section 1.1,- added clarification for sub-aims 2a and 2b for study Aim 2 with the 
following statement:  “As an exploratory analysis, we will compare the effectiveness of 
Phase II treatments separately for patients non-responsive to PT and patients non-
responsive to M2H”  
iv) Section 7.6 – Safety Monitoring, Composition of DSMB section – updated to reflect that 
the NCCIH appointed the Board members 
v) Section 7.6 – Frequency and Character of DSMB Meeting – updated to clarify that the 
NCCIH biostatistician attends the closed session, consistent with the DSM plan. 
vi) 
Section 9.1 – clarified that the sub-aims for Aim 2 will be considered exploratory 
analyses 
vii) 
Section 9.2 – updated total sample size to 850 from original sample size of 1,200. Also 
corrected minimum detectable effects based on revised sample size 
viii) Section 9.2 – Power table updated to reflect revised sample size of 850. 
ix) 
Section 9.6 - Data Analyses - clarified that Aim IIa and IIb will be considered 
exploratory

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STUDY TEAM ROSTER  
The University of Utah 
Julie Fritz, PhD, PT 
Distinguished Professor, Dept. Physical 
Therapy & Athletic Training 
Email: julie.fritz@utah.edu 
Role: PI 
 
Tom Greene, PhD 
Professor, Dept. Population Health Sciences  
Email: tom.greene@has.utah.edu 
Role: Co-Investigator, Bio-Statistician 
 
Jacob Kean, PhD 
Associate Professor, Dept. Population Health Sciences  
Email: Jacob.Kean@hsc.utah.edu 
Role: Co-Investigator 
 
Megan Vanneman, PhD 
Assistant Professor, Dept. Population Health Sciences  
Email: Megan. Vanneman@hsc.utah.edu 
Role: Co-Investigator 
 
Jaewhan Kim, PhD 
Associate Professor, Dept. Health, Kinesiology & 
Recreation 
Email: Jaewhan.Kim@utah.edu 
Role: Co-Investigator, Health Economist 
 
Eric Garland, PhD, LCSW 
Professor, College of Social Work 
Email: eric.garland@socwk.utah.edu 
Role: Co-Investigator 
 
Jincheng Shen, PhD 
Assistant Professor, Division of Epidemiology 
Email: Jincheng.shen@hsc.utah.edu 
Role: Co-Investigator 
 
Nora Fino, MS 
Division of Epidemiology 
Email: Nora.Fino@hsc.utah.edu 
Role: Statistician 
 
Department of Defense 
 
Dan Rhon, DSc, DPT, PhD 
Clinical Scientist, Center for the Intrepid  
BAMC, 3551 Roger Brooke Drive 
Email: daniel.rhon2.ctr@health.mil 
Role: PI 
 
Deydre Teyhen, PhD, DPT 
Chief, Army Medical Specialist Corps 
Office of the Army Surgeon General 
Falls Church, VA 
Email: deydre.s.teyhen.mil@health.mil 
Role: Co-Investigator 
 
Ian Lee, DSc, MPT, MHA 
Allied Health Staff Officer, Office of Surgeon General 
7700 Arlington Blvd, Falls Church, VA 22041 
Email: ian.e.lee.mil@health.mil 
Role: Co-Investigator 
 
Richard Thorp, MBA 
Deputy Chief and Lead Decision Scientist  
US Army Medical Command, Fort Sam Houston 
Email: richard.e.thorp.civ@health.mil 
Role: Co-Investigator 
 
Benjamin Keizer, PhD 
Rehabilitation Psychologist, Center for the Intrepid  
BAMC, 3551 Roger Brooke Drive 
Email: benjamin.m.keizer.mil@army.mil 
Role: Co-Investigator 
 
Rachel Mayhew, PT, DPT 
Research Physical Therapist, Center for the Intrepid 
BAMC, 3551 Roger Brooke Drive 
Email: rachel.j.mayhew.ctr@health.mil 
Role: Project Coordinator 
 
Kaitlyn S. Foster, PT, DPT 
Research Physical Therapist, Center for the Intrepid, 
Department of Rehab Medicine 
BAMC/WHASC, 3551 Roger Brooke Drive 
Email: kaitlyn.s.foster.ctr@health.mil 
Role: Project Coordinator 
 
Tina Greenlee, PhD 
Research Scientist, Center for the Intrepid,  
Department of Rehab Medicine, BAMC 
BAMC, 3551 Roger Brooke Drive 
Ph: 210-808-2575 
Email: tina.a.greenlee.ctr@health.mil 
Role: Research Assistant

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PARTICIPATING STUDY SITES 
1. Brooke Army Medical Center 
Fort Sam Houston, Texas 
Site PI – LTC Bryan Pickens 
bryan.b.pickens.mil@health.mil 
Research Coordinator – Tina Greenlee, PhD 
tina.a.greenlee.ctr@health.mil 
 
2. Wilford Hall Ambulatory Surgical Center 
Lackland Air Force Base, Texas 
Site PI – Lt Col Alden Taylor 
alden.L.taylor.mil@health.mil 
Research Coordinator – Kaitlyn Foster, PT, DPT 
kaitlyn.s.foster.ctr@health.mil 
 
3. Madigan Army Medical Center 
Joint Base Lewis-McCord, Washington 
Site PI – COL Lisa Konitzer 
lisa.n.konitzer.mil@health.mil 
Research Coordinator – Rachel Mayhew, PT, DPT 
rachel.j    rachel.j.mayhew.ctr@health.mil 
 
4. Desmond Doss Health Clinic, Schofield Barracks 
Tripler Army Medical Center, HI 
    Site PI – MAJ Garry Dredge 
    garry.f.dredge.mil@health.mil 
Research Coordinator - Paola Olvera    
Maria.p.olvera.ctr@health.mil 
 
5. CLOSED: Carl R. Darnall Army Medical Center, 
Fort Hood, Texas 
   Site PI – N/A 
   Research Coordinator – N/A

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PRÉCIS  
Study Title: SMART Stepped Care Management for Low Back Pain in Military Health System  
Objectives  
Our objective is to conduct a SMART trial comparing effectiveness and cost-effectiveness of Phase 1 
and 2 treatments in a Stepped Care approach for patients with chronic LBP in the MHS with patient-
centered and healthcare cost outcomes. Sub-aims will compare main effects of Phase 1 and 2 treatment 
options and the sequencing effects of different treatment combinations. 
Specific Aims 
Our primary Aims are to compare the effectiveness of the Phase I treatments in the full patient 
population and of the Phase II treatments among non-responders to the Phase I treatments: 
I.   Compare the effectiveness of Physical Therapy (PT) vs. Move to Health (M2H) as Phase I options 
for chronic LBP on patient outcomes at 8 weeks. 
II.  Among patients non-responsive to Phase I treatment with PT or M2H, compare the effectiveness 
and evaluate cost-effectiveness of treatment with combined M2H+PT vs. Mindfulness as a Phase II 
interventions on patient outcomes at 26 weeks. 
Secondary Aims will compare the effectiveness of the Phase I treatments when followed by Mindfulness 
or by combined PT+M2H for Phase I non-responders (Aims IIIa and IIIb). We will also compare the 
four embedded 2-stage treatment strategies (Aim IV). Finally, we will examine the comparisons of Aims 
I-IV within pre-specified patient sub-groups (Aim V).   
III.  Compare the effectiveness of the Phase I treatments when followed by Mindfulness or by 
combined PT+M2H for Phase I non-responders. 
IV.  Determine which of the four embedded 2-stage treatment strategies provides the optimal average 
outcomes at weeks 18, 26 and 52 for the patient population with chronic LBP in the MHS. The 2-
stage treatment strategies are; a) PT followed by Mindfulness in non-responders, b) PT followed 
by PT+M2H in non-responders, c) M2H followed by Mindfulness in non-responders, and d) M2H 
followed by PT+M2H in non-responders)  
V.    Evaluate objectives I-IV within sub-groups of patients defined by key baseline characteristics (sex, 
age, sleep disturbance, and baseline opioid use).  
Design and Outcomes   
This study will recruit active duty military members or members of Reserves or National Guard on 
active duty, family members of active duty personnel, or Tricare beneficiaries receiving care in a 
participating MHS facility, age 18-65, seeing a primary care provider with chronic LBP based on the 
NIH Task Force definition.145 Subjects meeting eligibility criteria and providing informed consent will 
be enrolled in a Sequential Multiple Randomization Trial (SMART) comparing the effectiveness and 
cost-effectiveness of Stepped Care pain management options, examining sequencing, and heterogeneity 
of effects in pre-specified subgroups. All participants will first receive 6 weeks of Phase I care with 
either physical therapy (PT) or Move to Health (M2H) interventions. Randomization to Phase I 
treatment will be stratified by site, gender and active duty status. After Phase I we will assess response 
to initial treatment strategy. Phase I responders will receive up to 2 additional sessions of treatment to 
facilitate a transition to self-management. Phase I non-responders will be randomly assigned to a more 
intensive Phase II treatment of either mindfulness or a combined PT+M2H intervention. Phase II 
randomization will be stratified by site, gender, active duty status and Phase I treatment assignment. 
Phase II will last for 8 weeks with follow-up assessments at 18 weeks (conclusion of Phase II), 6 months 

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and 12 months after enrollment. Outcomes include patient-reported measures and health care costs. The 
overall study design is outlined below.    
Interventions and Duration  
All participants will receive 6 weeks of Phase I treatment of either M2H or PT based on random 
allocation. After 6 weeks of treatment participants will be evaluated and determined to be a treatment 
responder or non-responder based on self-reported change from baseline on the primary outcome 
measure. Responders will continue with Phase I treatment receiving up to 2 additional treatment 
sessions during Phase II. Non-responders will be re-randomized to a more intensive Phase II treatment 
of either combined PT+M2H or mindfulness. Phase II treatment lasts for 8 weeks. The final follow-up is 
conducted 12 months after enrollment. Therefore the total time “on study” for a participant is 12 months. 
Sample Size and Population  
We will recruit a total of 850 participants age 18-65 with non-specific, chronic LBP. Participants will be 
randomized to a Phase I treatment (PT or M2H). Initial randomization will be stratified by site, gender 
and active duty status. Individuals determined to be non-responders to Phase I treatment will be re-
randomized to a Phase II treatment (PT+M2H or Mindfulness). Re-randomization will be stratified by 
site. Phase I responders will receive up to 2 additional sessions of the same treatment during phase II.     
1. STUDY OBJECTIVES 
1.1 Primary Objectives 
Our primary study objectives are to compare the effectiveness and cost-effectiveness of Phase I 
treatments and of Phase II treatments among non-responders. These objectives correspond to specific 
aims I and II (a and b) respectively: 
I. Examine the comparative effectiveness of PT vs. Move to Health as Phase 1 options for chronic 
LBP after 8 weeks.  
II. Among patients non-responsive to Phase I treatment with PT or M2H, compare the effectiveness 
and evaluate cost-effectiveness of treatment with combined M2H+PT vs. Mindfulness as a Phase II 
interventions on patient outcomes at 26 weeks. 

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As an exploratory analysis, we will compare the effectiveness of Phase II treatments separately for 
patients non-responsive to PT and patients non-responsive to M2H:  
IIa.  Among patients non-responsive to Phase 1 treatment with PT, examine the comparative 
effectiveness and cost-effectiveness of treatment with combined M2H+PT vs. Mindfulness as a 
Phase 2 interventions after 26 weeks. 
IIb.  Among patients non-responsive to Phase 1 treatment with M2H, examine the comparative 
effectiveness and cost-effectiveness of treatment with combined M2H+PT vs. Mindfulness as a 
Phase 2 interventions after 26 weeks. 
1.2 Secondary Objectives 
Our main secondary objectives are to compare the effectiveness of the Phase I treatments when 
followed by Mindfulness or by combining PT+M2H (specific aims III a and b). As an exploratory aim 
we will compare the 4 embedded 2-stage treatment strategies (specific aim IV). Finally, we will 
examine specific aims I-IV considering pre-specified patient sub-groups (specific aim V).   
III.  Compare the effectiveness of the Phase I treatments when followed by Mindfulness or by 
combined PT+M2H for Phase I non-responders. 
IIIa.  Compare the effectiveness of Phase 1 treatments (PT vs. M2H) with Mindfulness as Phase 2 
treatment. (Addresses if the effectiveness of Mindfulness is impacted by Phase 1 treatment). 
IIIb.  Compare the effectiveness of Phase 1 treatments (PT vs. M2H) with PT+M2H as Phase 2 
treatment. (Addresses if the effectiveness of M2H+PT is impacted by Phase I treatment – i.e., 
evaluates if temporal ordering of PT and M2H impacts effectiveness of combined treatment). 
IV.   Determine which of the 4 embedded 2-stage treatment strategies provides the optimal average 
outcomes for the patient population with chronic LBP in the MHS. The 2-stage treatment 
strategies are; a) PT followed by Mindfulness in non-responders, b) PT followed by PT+M2H in 
non-responders, c) M2H followed by Mindfulness in non-responders, and d) M2H followed by 
PT+M2H in non-responders)  
V.    Evaluate specific aims I-IV considering sub-groups of patients defined by key baseline 
characteristics (sex, age, sleep disturbance, and baseline opioid use).  
2. BACKGROUND AND RATIONALE 
2.1 Background on Condition, Disease, or Other Primary Study Focus 
Chronic pain is a ubiquitous and growing concern in both civilian and military populations. Incident 
rates of chronic pain diagnoses for active duty military members have increased over 3-fold, from 30.4 
to 107.8 per 10,000 person-years, from 2007 - 2014.4 More than half of veterans who served in 
Operation Enduring Freedom, Operation Iraqi Freedom and Operation New Dawn report chronic pain 
to their primary care provider.17 One report of active duty members returning from deployment found 
40% reported chronic pain lasting at least 3 months and more than half reported experiencing pain 
almost daily or constantly.5 Improving pain management is a priority for the VA and DoD as it has for 
civilian healthcare systems.6,18,3  
The most common chronic pain condition in the MHS and civilian healthcare is low back pain 
(LBP).17,19 About 70% of incident medical encounters for a primary diagnosis of chronic pain in active 
duty military members have LBP as the secondary diagnosis,4 highlighting the frequency with which an 
episode of LBP can transition to chronic pain. LBP is as prevalent among military personnel as with 
civilian populations.20 For active duty military, LBP has been the most common reason for a medical 
encounter every year since 2011, accounting for over 1 million encounters in 2015 involving 223,094 
individuals.10 Spinal pain is the 3rd costliest medical condition in the U.S. overall, behind only diabetes 
and heart disease, and LBP costs have been increasing at second fastest rate, trailing only diabetes.8 The 

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substantial economic burden imposed by LBP is evident in the MHS. Our research team examined direct 
medical costs for 753,450 episodes of care in the MHS following a new primary care consultation for 
uncomplicated LBP and found nearly $1 billion in 1-year LBP-related medical costs in these patients.14 
This figure excluded costs for patients with complicated, chronic LBP conditions, which would add 
considerably to the total medical costs for LBP in the MHS. An additional cost related to LBP for 
military personnel comes from the adverse impact on readiness. LBP is the leading cause of medical 
discharge across all military services9 and is one of the leading causes of seeking healthcare or being 
evacuated from a combat theater.10  
The prevalence and burden of chronic pain in the MHS makes the condition a priority for improvement. 
The 2010 report from the U.S. Army Pain Management Task Force (APMTF) provided 109 
recommendations to improve pain management.6 Based on the APMTF’s report, DoD developed a 
comprehensive pain management policy to address the quality and effectiveness of care within the 
MHS.15 The policy recognizes the importance of pain management at both the primary care and 
specialist levels, supporting implementation of Veterans’ Health Administration’s Stepped Care Model 
of Pain Management.1,18 Stepped care is a strategy to provide a continuum of evidence-based treatment 
across stages of pain management, emphasizing an individualized, stepwise approach as patients 
increase in complexity or fail to respond with less intensive interventions.12   
Stepped care models are attractive because they begin with lower cost, less intensive, more accessible 
interventions. More costly, intensive treatments are used for those who are not receiving sufficient 
benefit. This strategy has been beneficial for other conditions such as depression that are highly 
prevalent and characterized by many patients who are responsive to evidence-based, lower intensity 
interventions.34 Providing intensive services to all individuals with a prevalent condition such as LBP 
overwhelms the delivery system and needlessly escalates costs.  
Efforts to improve chronic LBP management align with DoD Pain Management policy recommendations 
for a Stepped Care approach. The VA//DoD LBP practice guideline also endorses stepped care beginning 
in primary care and advancing based on patient’s responsiveness.22,35-38 A key challenge in implementing 
stepped care for LBP comes from the large number of interventions encompassed by each Step and a 
lack of information on comparative effectiveness, treatment tailoring and sequencing within Steps. Lack 
of guidance on what treatments to choose for a particular patient is a primary motivation for this project.  
2.2 
Study Rationale 
Improving non-pharmacologic management of chronic pain is a priority for the MHS. Low back pain is 
the most common diagnosis precipitating a chronic pain condition. Improved LBP management could 
therefore exert a substantial impact on chronic pain in the MHS. The Army Pain Management Task 
Force recommends implementation of the VA Stepped Care Model of Pain Management. Stepped Care 
emphasizes a continuum of evidence-based treatments beginning with less intensive options; proceeding 
to higher-intensity care for patients who do not respond.12 Various options exist at each step with little 
information on tailoring or sequencing treatments to optimize outcomes and manage costs.13 Step 1 is 
primary care-based. Physical therapy (PT) is often integrated at this step.14 Step 1 is also the stage where 
integration of a holistic approach to health may be beneficial. The Office of the Army Surgeon General 
has promoted the Move to Health (M2H) program as a strategy to bring a holistic perspective into 
healthcare to empower and engage patients in self-care with the support of an integrated team. For 
patients non-responsive to Step 1, Step 2 advocates more intensive or specialized care.15 Mindfulness-
based treatments show promise13 for patients with chronic LBP requiring specialized care due to post-
traumatic stress or post-concussive symptoms; a common post-deployment triad.16 A combination of PT 
and M2H may also benefit initially non-responsive individuals.  
The MHS has existing resources (e.g., PT) and strategic initiatives (e.g., M2H, integrative care including 
mindfulness) that can be leveraged to realize the goal of Stepped Care. Key questions exist however 

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about the relative effectiveness of various strategies at different Steps, how to sequence treatments and 
individualize care based on specific patient characteristics and the resource implications. These key 
questions have informed the development of our Project. Addressing these questions can improve 
chronic LBP management throughout the MHS and provide lessons to inform strategies for other pain 
conditions. 
3.  STUDY DESIGN 
We will use a sequential multiple randomization (SMART) design (figure 1). We will compare the 
effectiveness of Phase I treatments for chronic LBP: PT or M2H. Phase I treatment will be 6 weeks in 
duration with re-evaluation at 8-weeks post-enrollment to allow time to initiate and complete treatment. 
At the 8-week re-assessment we will examine if the patient has responded to initial treatment using a 
patient-centered definition of successful response based on change in the primary outcome measure. 
Patients who are responders to Phase I treatment will receive up to 2 additional sessions of the same 
treatment to assist transition to self-management. Non-responders will be re-randomized to a second, 
Phase II strategy of either combining the initial treatments (PT+M2H), or mindfulness. The second 
treatment phase is 8 weeks in duration. Patient-centered outcomes will be collected at re-evaluations 
occurring 18 weeks (post-Phase II treatment), 6 and 12 months after enrollment using a web-based 
platform to collect outcome variables. Direct medical costs related to LBP treatments over the 1-year 
follow-up period will be extracted from the Military Data Repository (MDR) and Military Operational 
Data Systems (MODS) databases at the conclusion of the participant’s time in the study. 
4.  SELECTION AND ENROLLMENT OF PARTICIPANTS  
4.1 Inclusion Criteria 
Subjects in this study must satisfy all of the following eligibility criteria: 
1. Active duty military member (Army, Navy, Air Force, Marines) or member of Reserves or National 
Guard on active duty, family member of active duty personnel, or Tricare beneficiary receiving care 
in a participating MHS facility. 
2. Age 18 – 65 years at the time of enrollment. 
3. Receiving Step 1 chronic LBP care based on VA Stepped Care Pain Management model defined as: 
a. Seen by a health care provider for chief complaint of LBP with or without symptoms into the 
buttocks or legs within past the 30 days.  
- Chief complaint of LBP which may be self-reported or identified by primary ICD-10 code of 
LBP (M54.5, M54.9, S33.012), lumbar degenerative change (M51.36, M51.37, M48.06, 
M47.817), lumbar disc herniation/radiculitis (M54.16, M54.17, M51.26, M51.27, M54.3).  
- Health care provider includes physicians, physician assistant, chiropractor or advanced practice 
nurse.   
b. May have received interventions for LBP including medication management or primary care-based 
education/counseling. 
4. Meets NIH Task Force145 definition of chronic LBP based on two questions: 1) How long has LBP 
has been an ongoing problem for you? and 2) How often has LBP been an ongoing problem for you 
over the past 6 months? A response of greater than 3 months to question 1, and “at least half the days 
in the past 6 months” to question 2 is required to satisfy the NIH definition of chronic LBP. 
5. Anticipates ability to attend treatment sessions over a 16 week period following enrollment with no 
planned absence of 2 weeks or more for training, vacation or any purpose. 
4.2 
Exclusion Criteria 
Any subject meeting any of the following exclusion criteria at baseline will be excluded from the study. 

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1. Signs of serious or systemic pathology as a cause of LBP including spine fracture, neoplasm, 
inflammatory disease (e.g., ankylosing spondylitis), vertebral osteomyelitis, etc. 
2. Knowingly pregnant  
3. Has received interventions for LBP that involves providers other than primary care in the past 6 
months. This includes physical therapy or behavioral pain management or counseling as well as 
specialist physician consultations, chiropractic, etc. 
4. Has received any interventional pain procedures (e.g., spinal injections), inter-disciplinary pain 
management, integrated chronic pain and substance use treatment programs, etc. in the past 6 months 
5. Has received any spinal surgery in the past year. 
6. Pending a medical evaluation board, discharge from the military for medical reasons, or pending or 
undergoing any litigation for an injury.   
7. At elevated acute risk for suicide (i.e., risk is below the level requiring either consultation or urgent 
action based on VA/DoD Clinical Practice Guideline for Assessment and Management of Patients at 
Risk for Suicide)173 
4.3 
Study Enrollment Procedures  
Participant recruitment will occur using complimentary strategies to ensure participation is offered to a 
representative cohort. Providers and staff from primary care or other health care provider clinics at 
participating sites may alert research staff when they see patients with a diagnosis of chronic LBP. The 
majority of patients schedule an appointment within 72 hours of the appointment time, therefore 
clinicians and research staff will be able to see a roster of patients with a reason of “back pain” listed 
before the appointment. The list of scheduled patients appears in AHLTA, the electronic medical record 
system used by the DoD. A HIPAA waiver allows approved research staff to review the appointment list 
in AHLTA. Scheduled patients with LBP may be called and notified of the study and their potential 
eligibility. If interested in further information, the patient is asked to arrive 15 minutes prior to the 
scheduled provider appointment. Patients interested in more information will be taken to a private room 
and an approved member of the research team will explain the nature and purpose of the study 
including: follow-up times, requirements, and the nature and type of data collected. A researcher will 
meet with patients interested in participation either before or after their provider appointment to continue 
with the informed consent process and eligibility screening.  
Recruitment may also occur via the MOTION platform. As part of standard care, patients attending 
participating MHS facilities are asked by clinic staff to enter their DoD Identification Number into the 
tool (on a computer, tablet or phone), which creates a case based on the patient’s primary complaint. A 
clinician is assigned to the case and sent an e-mail link that allows input of evaluation and intervention 
data related to the case. For patients with a chief complaint of LBP consenting to be part of the outcomes 
registry at a primary care visit, approved research staff will review and notify individuals of their 
potential eligibility unless participation was previously offered. Patients interested in more information 
will meet with a researcher to continue with the informed consent process and eligibility screening.  
We will track the status of all individuals with whom participation is discussed in a study screening log. 
For each individual who discusses participation but does not enroll in the study we will record the 
reason for ineligibility, or if eligible the reason for declining participation. The screening log will be 
maintained in RedCap. A separate log will be maintained at each study site. Randomization will occur 
through the RedCap randomization module. A study statistician will create randomization allocation 
tables for the initial random assignment to Phase I treatment group and a separate allocation table for re-
randomization of non-responders to a Phase II treatment group. Allocation tables are prepared by a study 
statistician using SAS software and will upload these tables into the RedCap project site. The initial 

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randomization will occur after completion of all consent and baseline evaluation procedures. After 
baseline data are input RedCap will display a "Randomize" button in the data entry screen. This button 
allows the researcher to generate a random intervention group assignment based on the randomization 
allocation table. 
5. STUDY INTERVENTIONS  
5.1 
Interventions, Administration, and Duration  
The study interventions are provided across two treatment phases. Phase 1 treatment will begin after 
enrollment and completion of all baseline assessment procedures. In Phase I participants will be 
randomly assigned to receive either the Physical Therapy or Move 2 Health intervention. Phase I 
treatment period will last for 6 weeks. At the 8-week assessment participants will be judged to be 
treatment responders or non-responders based on responses to patient-reported outcomes. Participants 
determined to be responders to Phase I treatment will be permitted up to 2 additional sessions of their 
randomly assigned Phase I treatment during Phase II to facilitate transition to self-management. 
Participants determined to be non-responders will be re-randomized to a Phase II treatment of either 
mindfulness or a combined PT+M2H intervention. Phase II treatment will last for 8 weeks.  
This study is designed to be a pragmatic clinical trial. Therefore, we are permitting flexibility for 
providers in determining the precise dosage and administration of all interventions. Parameters are 
provided within which pragmatic intervention decisions can be made by providers based on individual 
participant’s needs. These parameters are described for each treatment in the following sections. 
Detailed instructions are provided in the Manual of Operations for each intervention (see Appendix II). 
5.1.1  Physical Therapy 
Participants randomized to receive Physical Therapy (PT) during Phase I will be referred to the physical 
therapy clinic at the participating MHS facility. Physical therapy interventions will be managed by a 
licensed physical therapist who may be an active duty or employed civilian physical therapist. The 
directing physical therapist must have received training in study-related procedures. The initial PT 
treatment session will occur within 7 days of enrollment in the study. Consistent with a pragmatic study, 
the precise dosage (i.e, number of PT sessions) will be at the discretion of the physical therapist 
directing the participant’s care, up to a maximum of 2 sessions per week over the 6-week Phase I 
treatment period. Subsequent care beyond the initial PT treatment may be provided by physical therapy 
support personnel working at the MHS facility (e.g., physical therapy assistants or aides).  
As part of study-related training, managing physical therapists will be trained to guide the dosage and 
type of activities using an evidence-based risk stratification tool.133 Evidence-based risk stratification 
involves identifying physical and psychological factors associated with prolonged disability and 
tailoring treatments to address the factors present in an individual patient.134 The 9-item STarT Back 
screening tool (SBST) is an evidence-based risk stratification tool that categorizes patients into 1 of 3 
risk groups for persistent disability (low, medium, high) with treatment and dosage tailored to each 
category.136 The low risk category receives care focused on education. Medium risk receives education 
along with exercise and spinal manipulative therapy to address physical factors. High risk receives 
education, exercise and spinal manipulative therapy supplemented by principles of cognitive-behavioral 
therapy to address psychological.137 The SBST will be administered as part of the baseline assessment 
by a member of the research staff. The following actions will be taken based on the SBST category for 
the patient: 
• Low Risk:  Researcher will provide education and contact patient by phone, text or e-mail after 2 
weeks. The need for follow-up PT sessions will be determined at that time. 
• Medium Risk:  Researcher will schedule patient for follow-up PT with referral noting medium risk 
status.  

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• High Risk:  Researcher will schedule patient for follow-up PT with referral noting high risk status.   
Follow-up PT care will be focused on providing evidence-based physical therapy interventions including 
patient education and physical treatments.13 Patient education in a biopsychosocial model of pain is 
advocated by LBP guidelines and the Stepped Care Model.22 The DoD/VA LBP guideline22 identify 
exercise and spinal manipulative therapy as evidence-based physical treatments provided by physical 
therapists, with provision and dosage matched to patients’ risk for persistent disability.35,130-132 
Consistent with a pragmatic study, the specific activities provided during PT sessions with an individual 
participant will be at the discretion of the managing physical therapist.  
5.1.2  Move to Health (M2H) 
Participants randomized to receive Move to Health (M2H) during Phase I will first receive education 
using video and written materials to introduce the key domains of holistic health in the M2H model and 
their relationship to chronic LBP. The domains include the following:  
• Sleep 
• Physical Activity (movement, strength, endurance and agility) 
• Nutrition 
• Intrinsic Well-Being (Personal Development, Spiritual Well-Being, Emotional Well-Being) 
• Extrinsic Well-Being (Family/Social Relationships, Surroundings) 
After reviewing education materials guided by a member of the research staff, the participant will 
complete a Personal Health Inventory. The Inventory will be reviewed by the researcher and patient in 
order to identify a specific domain of holistic health the patient would like to prioritize and focus on in 
follow-up treatment. Once the domain is identified, additional domain-specific screening will be 
completed. Follow-up care will be based on the level of need identified by domain-specific screening, 
and may range from guided self-management with the researcher to a specialist referral (e.g., sleep 
specialist, dietician, behavioral health provider, etc.). 
Consistent with a pragmatic study, the precise dosage (i.e, number of M2H sessions) will be at the 
discretion of the clinicians directing the participant’s care, up to a maximum of 2 sessions per week over 
the 6-week Phase I treatment period. Sessions may be delivered in-person or utilize technology 
including text messaging, telephone, e-mail, skype, app-based self-management etc.  
5.1.3  PT+M2H 
Participants randomized to receive a combination of PT and M2H as a Phase II intervention will 
continue their Phase I treatment (either M2H or PT). The participant will begin the treatment component 
that was not part of their Phase I intervention using the procedures outlined in the Phase I descriptions. 
The provider of the participant’s Phase I intervention will be informed that the other component is being 
added to treatment. 
5.1.4  Mindfulness  
Participants randomized to receive mindfulness as a Phase II intervention will discontinue their Phase I 
treatment. The mindfulness program that will be used in this study is Mindfulness-Oriented Recovery 
Enhancement (MORE). The MORE treatment was designed specifically to address symptoms and 
underlying mechanisms of chronic pain in the military context. MORE is designed to be provided in 8 
individual sessions with a behavioral health provider trained by the study investigators to provide the 
MORE treatment. Behavioral health providers may be psychologists, advanced practice nurses, social 
workers or other licensed providers with behavioral health training. Throughout the 8 MORE 
intervention sessions, three core areas are emphasized as outlined below. Activities include exercises 

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and at-home work for participants to reinforce these core areas. 
• Mindfulness. Participants will be guided in each within-session mindfulness practice to: a) become 
aware of when their attention is being engaged by pain, uncomfortable physical sensations, and 
aversive thoughts and feelings; b) acknowledge and accept that this attentional engagement has 
occurred (“It’s okay to have these thoughts and feelings, because I don’t have to react to them!”); 
and c) disengage attention from pain and aversive experience, and then shift and engage attention to 
neutral or health-promoting stimuli via the practice of mindful breathing. 
• Cognitive reappraisal. After cognitive restructuring is introduced in Session 3, week, patients will 
be queried about their use of mindfulness to become aware of and decenter from automatic 
thoughts, challenge automatic thoughts, and become open to new, more adaptive appraisals. 
• Savoring of positive experiences. After savoring of pleasant experiences is introduced in Session 4, 
patients will be queried about their use of mindfulness to become aware of, focus their attention on, 
and savor day-to-day positive experiences (e.g., the taste of an enjoyable meal, a beautiful sunset, 
nice weather, etc.). 
5.2   Handling of Study Interventions  
Consistent with a pragmatic trial, neither participants nor providers will be blinded to the interventions 
received. We will evaluate the dose of each study intervention as the number of sessions attended during 
the respective intervention periods. The number of study sessions will be recorded in RedCap based on 
the fidelity checklist completion as noted below. We will also evaluate provider fidelity to interventions. 
Direct observation is considered the gold standard of fidelity assessment, but is impractical for a large 
pragmatic study. Clinician self-reported fidelity can provide an efficient and acceptable alternative, 
particularly when focused on interventions’ core components with checklist formats.163 We will employ 
clinician-reported fidelity checklists to identify if core components and essential elements of each study 
intervention are provided to participants. Fidelity checklists will be completed through RedCap. Detailed 
instructions on the core components of each intervention and corresponding checklists are provided in 
the Manual of Operations for each intervention (see Appendix II).  
5.3   Concomitant Interventions  
Consistent with a pragmatic study, we will record all concomitant interventions. We will advise 
participants on the purpose of the study and the concomitant interventions considered allowed and 
prohibited based on the study’s goals. We will not remove any participant from the study for receiving a 
prohibited intervention. We will record the occurrence of any prohibited intervention during the study 
intervention period as a protocol deviation.  
5.3.1   Allowed Interventions 
Concomitant interventions permitted during the study intervention period include use of medication to 
control LBP symptoms (NSAIDs, muscle relaxants, opioids, etc.) The use of various medications will be 
recorded at the baseline examination and through the MDR records across the study period. Visits to 
health care providers for LBP are allowed during the study period (e.g., physician visits) as long as no 
interventional procedures (e.g., spinal injections, surgery, etc.) or mind-body interventions inconsistent 
with the participant’s assigned intervention group (e.g., chiropractic, acupuncture, etc.) are received. 
5.3.2   Prohibited Interventions 
Prohibited concomitant interventions during the study intervention period include any interventional 
procedures or mind-body interventions not consistent with the participant’s assigned intervention group 
including chiropractic care, massage therapy, acupuncture, spinal injections, surgical procedures, etc. If 
any prohibited events occur these will be recorded as protocol deviations. Subjects will continue to 
participate in study-related treatments and assessments unless the off-protocol intervention changes the 
risk-benefit profile for the participant. 

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5.4 
Adherence Assessment  
Treatment adherence will be evaluated based on attendance at scheduled treatment sessions and 
compliance with core components for each intervention group at attended sessions from provider self- 
report checklists. AHLTA and checklists will be used to determine the number of intervention sessions 
attended by each participant. For attended sessions, the provider will complete an intervention core 
component checklist and provide rationale for non-adherence or off-protocol interventions. All off-
protocol events will be recorded, such as use of techniques or procedures not outlined in the protocol.  
For purposes of per-
protocol analyses we 
will define adherence 
as occurring when a 
participant attends the 
initial session in their 
randomly assigned 
phase I or II 
intervention group. We 
will define adherence 
in the PT group based on attendance at PT sessions consistent with the SBST risk profile for the 
participant. In the M2H group we will define adherence based on completion of the PHI and attendance 
at follow-up referral/ session. In the MORE mindfulness group we will define adherence based on 
attending at least 6 of a possible 8 sessions. Specific definitions of adherence are outlined in the table. 
5.5    Considerations for Future Implementation 
The study interventions are designed to be pragmatic and potentially scalable across military treatment 
facilities depending on the results of this study. The interventions are designed to be scalable by 
capitalizing on existing resources including services and providers available at most military treatment 
facilities. We have detailed training manuals (see Appendix II) outlining provider training and 
intervention parameters. We are working with the current directors in primary care at our participating 
sites. We anticipate turnover in these positions throughout the study period and will continue to engage 
with incoming directors.  
With respect to implementation of study findings at the policy level within DoD, we have engaged key 
stakeholders both as members of the investigator team and through outreach at the participating sites. 
Col. Deydre Teyhen, member of the investigator team, leads the stakeholder engagement efforts. Col. 
Teyhen is currently Commander at the Walter Reed Army Institute of Research. She is also a licensed 
physical therapist and she has served as the Deputy Chief of Staff for Public Health for the Office of the 
Surgeon General. In this role she led the development and implementation of the Performance Triad, 
Move To Health, and other programs to assist Army Medicine in transitioning from a Healthcare System 
to a “System for Health”. LTC Ian Lee, also a member of the investigator team, serves as Allied Health 
Staff Officer within the Office of the Surgeon General at the Defense Health Agency (DHA). 
Specifically, LTC Lee works within the Rehabilitation & Reintegration Division at DHA, which 
provides policy guidance related to rehabilitation, reintegration, psychological resilience and pain. 
Continued communication with these policy bodies will facilitate dissemination of the study findings 
and create opportunities for implementation as appropriate based on the results.     
 
 
Treatment Group Definition of “Adherence” 
Physical Therapy 
Low Risk – attend 1-3 sessions 
Medium Risk – attend 4-8 sessions 
High Risk – attend 6-12 sessions 
M2H 
Attend initial Health Coaching session and complete the 
Personal Health Inventory. Complete the assigned 
follow-up session or referral following initial session 
MORE Mindfulness Attend at least 6 of 8 weekly sessions 

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6. STUDY PROCEDURES  
6.1 Schedule of Evaluations 
OUTCOME 
Screening 
Assessment 
Baseline 
Assessment 
(day 0) 
8 weeks 
(post Phase I) 
(day 50 – 66) 
18 weeks 
(post Phase II) 
(day 120– 140) 
26 weeks 
(day 180 – 200) 
52 weeks 
(day 360 – 380) 
Informed Consent Form   
X 
 
 
 
 
 
Eligibility Criteria 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
COVID-19 impact survey 
X 
 
 
 
 
 
Randomization 
 
X 
X 
(non-responders) 
 
 
 
Start Back Screening Tool (SBST) 
 
X 
X 
 
 
 
Patient Acceptable Symptom State  
 
X 
X 
X 
X 
X 
PROMIS Pain Interference CAT 
 
X 
X 
X 
X 
X 
PROMIS Physical Function CAT 
 
X 
X 
X 
X 
X 
PROMIS Sleep Disturbance CAT 
 
X 
X 
X 
X 
X 
PROMIS Depression CAT 
 
X 
X 
X 
X 
X 
PROMIS Anxiety CAT 
 
X 
X 
X 
X 
X 
PEG-3 
 
X 
X 
X 
X 
X 
EuroQol-5D 
 
X 
X 
X 
X 
X 
Perceived Readiness for Duty (active duty 
only) 
 
X 
X 
X 
X 
X 
Defense & Veterans Pain Rating Scale 
 
X 
X 
X 
X 
X 
Pain Body Diagram 
 
X 
X 
X 
X 
X 
Treatment Side Effects 
 
 
X 
X 
 
 
 Use of nonpharmacological and self-care 
approaches (NSCAP) 
 
 
 
 
 
X 
Limited Duty Days (active duty only) 
 
 
 
 
 
X 
Long-Term Opioid Use 
 
 
 
 
 
X 
Direct Medical Expenses 
 
 
 
 
 
X 
 
Collected within MOTION or REDCap 
 
Collected administratively through MDR or MODS 
6.2 Description of Evaluations  
6.2.1   Screening Evaluation 
Individuals who meet with a site Research Assistant will be provided information about the study. The 
Researcher will confirm that the individual meets the eligibility criteria for participation. If the 
individual meets these eligibility criteria and is interested in participation, he or she will undergo the 
consenting process outlined below. The individual may begin the consenting process either at that time 
or within 7 days of eligibility confirmation. 
  6.2.1.1   Consenting Procedure 
Individuals potentially eligible and interested in participation will be provided a written informed 
consent document using a form approved by the site IRB. The consenting process will be conducted by a 
Research Assistant who is trained by the Investigators and has completed Biomedical Research Training 
for Human Subjects research through the Collaborative Institutional Training Institute (CITI) which 
includes modules on human subjects research ethics and regulations related to informed consent. The 
Research Assistant will be available throughout the consenting process to explain the study and answer 
questions. The voluntary nature of the participation will be stressed, and participants will be reminded 

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that they may elect to withdraw from the study at any time. Participants will be assured that a decision 
not to participate will have no impact on their military status or ability to access health care.  
Individuals will be provided two copies of the informed consent document for signature. One copy of 
the signed informed consent document will be retained by the researchers and the other will be given to 
the participant. A single consent form will be used for the project. The Research Assistant consenting 
the participant will sign an Informed Consent Form checklist which will be retained by the researchers. 
 6.2.1.2  Screening 
Once informed consent is obtained the following screening procedures will be completed within 72 
hours to insure eligibility: 
• Confirm age on the date of consent is between 18 – 65 years old. 
• Confirm participant is not knowingly pregnant. 
• Confirm participant is not currently receiving, and has not receive in the prior 6 months, interventions 
for their LBP other than those provided in primary care. 
• Confirm participant has not received any interventional pain procedures, pain management or 
integrated pain management and substance use treatment programs in prior 6 months. 
• Confirm participant has not received any spine surgery procedures in the prior 1 year. 
• Confirm participant is experiencing LBP defined as pain between the 12th ribs and buttock with or 
without symptoms in the buttock(s) or leg(s) without “red flags” suggesting a possible non-
musculoskeletal cause (unexplained weight loss, night pain, systemic illness) 
• Confirm participant meets NIH definition of chronic LBP based on two questions: 1) How long has 
LBP has been an ongoing problem for you? and 2) How often has LBP been an ongoing problem for 
you over the past 6 months? Responses of “greater than 3 months” and “at least half the days in the 
past 6 months” to questions 1and 2 respectively are required to meet the definition of chronic LBP. 
• Confirm the participant is not at elevated acute risk for suicide based on VA/DoD Clinical Practice 
Guideline.173 The Guideline specifies that any individual with recent suicidal ideation or thoughts is 
at elevated risk. There is no evidence-based screening tool for elevated risk, and ongoing attention to 
expression of suicidal ideations or thoughts is recommended. We will ask if the participant has had 
any thoughts about harming him/herself. If the response is yes, or if these thoughts emerge at any 
point during participation in the study staff personnel will follow standard procedures to address 
safety issues and obtain appropriate care.  
Individuals meeting all eligibility criteria will proceed with study participation. Individuals who are 
ineligible after all screening procedures will be advised to return to primary care for continued pain 
management as necessary. Consistent with DoD Guidelines,175 study personnel will be trained to inform 
a participant’s primary care provider if concerns of an acute stress disorder are detected and access site-
specific emergency mental health care.  If risk factors for self-harm or danger to others are identified, 
acute management procedures (direct observation, limit access to lethal means and escort to 
urgent/emergency care) will be implemented. 
6.2.2   Enrollment, Baseline, and/or Randomization 
6.2.2.1  Enrollment 
This study uses a single informed consent document for both screening and treatment purposes. Thus the 
enrollment date is the date on which the consent document is signed and eligibility confirmed. We 
anticipate that screening will be completed on the same day for the majority of participants because of 
the relatively simple and quick screening procedures required. At the latest screening will be completed 
within 72 hours of providing informed consent. 

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6.2.2.2  Baseline Assessments 
Assessments involve collection of participant-reported and researcher-reported data. Patient-reported 
outcome (PRO) measures will be collected using an electronic platform (MOTION or REDCap) based 
on availability. The Military Orthopaedics Tracking Injuries and Outcomes Network (MOTION), an 
initiative of the Rehabilitation and Reintegration Division (R2D) of the Army Office of the Surgeon 
General, is a web-based application for collecting PROs that allows participants to input information 
from any internet-enabled device. MOTION is programmed to survey enrolled patients on a regular 
schedule that corresponds to the study Schedule of Evaluations outlined above for assessments through 
the 6-month assessment. Once enrolled, researchers may “push” a MOTION survey to participants. If 
surveys are not received the Wounded, Ill and Injured Registry (WIIR) is programmed to send a survey 
corresponding to the 8- and 18-week assessment time windows.  
REDCap (Research Electronic Data Capture) is an NIH-supported, browser-based, software solution 
that uses secure online forms for data capture, management and analysis. Participants and researchers 
can input data directly into REDCap and participants can also be sent surveys electronically for 
completion. We will also create functionality in REDCap to permit all study assessments to be collected 
through this platform. Research assistants at each site will track participants’ data collection completion 
to avoid duplication of surveys from different platforms. If a participant is unable to directly input data 
using a computer paper forms will be available with data input into the study database at a later time.  
The following assessments are collected at baseline: 
• Demographic/Medical History data will include age, gender, physical activity level, race/ethnicity 
and general medical and LBP history. Current medication use for LBP will be recorded. This 
information will be used for descriptive purposes and possible covariates in analyses. 
• Patient Acceptable Symptom State (PASS):  The PASS is a single-item self-assessment of the 
acceptability of the patient’s current symptom status.146 The PASS question is; “Taking into 
account all the activities you have during your daily life, your level of pain, and also your 
functional impairment, do you consider the current status of your low back satisfactory?”  The 
PASS permits patients to determine if their symptoms are acceptable in their own assessment.  
• PROMIS Pain Interference CAT (PI-CAT): Computer-adapted assessment using a 44-item bank 
measuring the self-reported consequences of pain on relevant aspects of life including impact on 
social, emotional, cognitive, physical and recreational activities. All PROMIS scores are reported 
on a T-score metric with a score of 50 points aligning with the general population mean and a 
standard deviation of 10. Higher scores indicate greater pain interference. 
• PROMIS Physical Function CAT (PF-CAT):  Computer-adapted assessment using a 121-item bank 
measuring current, self-reported capability related to physical activities. All PROMIS scores are 
reported on a T-score metric with a score of 50 points aligning with the general population mean 
and a standard deviation of 10. Higher scores indicate greater physical function. 
• PROMIS Sleep Disturbance CAT: Computer-adapted assessment using a 27-item bank measuring 
qualitative aspects of sleep and wake function.65 The score is reported on a T-score metric with a 
score of 50 points aligning with the general population mean and a standard deviation of 10. Higher 
scores indicate greater sleep disturbance. 
• PROMIS Depression CAT: Computer-adapted assessment using a 28-item bank measuring 
affective and cognitive manifestations of depression.64 The score is reported on a T-score metric 
with a score of 50 points aligning with the general population mean and a standard deviation of 10. 
Higher scores indicate greater levels of depression. 
• PROMIS Anxiety CAT: Computer-adapted assessment using a 29-item bank measuring fear (e.g., 
worry, feeling of panic), anxious misery (e.g., dread), hyperarousal (e.g., tension, nervousness, 

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restlessness) and somatic symptoms related to arousal (e.g., cardiovascular symptoms, dizziness).64 
The score is reported on a T-score metric with a score of 50 points aligning with the general 
population mean and a standard deviation of 10. Higher scores indicate greater levels of anxiety. 
• EuroQol (EQ-5D): A generic quality of life instrument covering 5 domains: mobility, self-care, 
usual activities, pain/discomfort, and anxiety/depression.155 Domain scores are combined to 
produce a health state ranging from 0 (death) to 1 (perfect health) which is commonly used in 
economic evaluation of clinical trials.156  
• Perceived Readiness for Duty: We have used 3 questions in prior studies to assess a service 
member’s self-perceived ability to perform military related tasks (pass a required semi-annual 
physical fitness test, operate under full combat load, and % mission capability).98 These questions 
will be used to assess participants who are active duty military members.  
• Defense and Veterans Pain Rating Scale (DVPRS):  Pain assessment tool utilizing a numeric pain 
rating for pain intensity and four supplemental questions reflecting pain interference with sleep, 
mood, usual activities and stress.159  The numeric rating scale uses a 0-10 rating scale with o 
representing “no pain” and 10 representing “pain as bad as it could be, nothing else matters”. 
Interference items are assessed on 0-10 Likert-scale rating anchored by 0 (pain does not interfere 
with or contribute) to 10 (pain completely interferes or contributes a great deal).157,158   
• Pain Body Diagram: A pain body diagram is used to quantify the extent and nature of painful 
symptoms throughout the body. The body diagram uses an outline of the body and permits the 
participant to indicate the location(s) perceived as painful and the type of symptoms present in each 
area.183  
• Pain, Enjoyment, and General Activity Scale (PEG-3): The PEG-3 measure includes 3 items 
evaluating 1) pain severity, and interference of pain with 2) enjoyment and 3) general activity. 
Response options for each item range from 0-10 and the PEG-3 score is expressed as the mean of 
all item scores.162 
6.2.2.3   Randomization 
Following baseline assessment all participants will be randomized to a Phase I treatment group (PT or 
M2H). A randomization allocation table will be developed prior to enrollment and integrated into 
REDCap by co-investigator Dr. Greene, Director of the Study Design and Biostatistics Center (SDBC) 
at the University of Utah. Blocked randomization with block sizes of 4 or 6 will be used. Randomization 
will be stratified based on site (MAMC, ,TAMC, BAMC, or WHASC), gender and active duty status 
(yes/no) to balance these variables.  
At the 8-week assessment the PI-CAT score will compared with the baseline score to determine if the 
participant is a “responder” to Phase I treatment or a “non-responder”.  An improvement from baseline 
of at least 7 T-score points will be required to be defined as a responder. All other participants will be 
considered a treatment non-responder. All non-responders will be randomized a second time following 
completion of all 8-week assessments. Randomization of non-responders to a Phase II treatment will be 
done through REDCap also based on an allocation table developed prior to enrollment using the same 
procedures outlined above. Phase II randomization will be stratified by sit, gender, active duty status and 
Phase I treatment group assignment.  
6.2.3   Blinding 
As is often the case in pragmatic clinical trials, participants and clinicians cannot be blinded to study 
treatments. Randomization assignment will not be revealed until baseline examination is complete to 
reduce potential bias by either the participant or researchers. The use of clinician-compliance audits 
during the study will allow for assessment of the impact of any differential treatment application.   

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Study statisticians cannot be blinded to participants’ study treatment assignments because they must 
complete Data Safety Monitoring Reports and analyze the study outcomes by treatment group. An 
unblinded study statistician will prepare aspects of the Data Safety Monitoring Reports that provide 
unblinded information for closed session consideration until such time that the study database is closed 
and locked. The randomization allocation tables will be developed before the study begins by 
statisticians who are not involved with managing the study databases. 
Follow-up assessments will be performed by a research assistant who will be blind to participants’ 
treatment group assignment. Participants will be reminded by the research assistant not to discuss 
aspects of their treatment during assessments. If a research assistant becomes unblinded during the 
course of a participant’s study participation, he or she will not be allowed to conduct additional follow-
up assessments. Instances of unblinding during an assessment will be recorded as an unexpected event.   
6.2.4   Follow-up Visits 
• Initial Phase 1 Treatment Visit (completed within the 7 days following day 0): 
o Treatment Session Form 
• Phase 1 follow-up Treatment Visits (completed between days 2-49): 
o Treatment Session Form 
• 8-Week Assessment (completed from Day 50 – Day 66): 
o Conducted in-person with an assessor blind to treatment group 
o Participant-reported questionnaires including PI-CAT to determine responder status 
o Participant-reported Treatment Side Effects Questionnaire 
• Phase II Treatment Visits - Responders (completed from Day 50 – Day 135, no more than 2 
additional visits of Phase I intervention): 
o Treatment Session Form 
• Phase II Treatment Visits – Non-Responders (completed from Day 50 – Day 135) 
o Treatment Session Form 
• 18-Week Assessment (completed from Day 120 – Day 140): 
o Conducted in-person with an assessor blind to treatment group 
o Participant-reported questionnaires 
o Participant-Reported Treatment Side Effects Questionnaire 
• 26-Week Assessment (completed from Day 180 – Day 200): 
o Conducted remotely through RedCap link sent by e-mail or text to participant 
o Participant-reported questionnaires 
6.2.5   Completion/Final Evaluation 
The final evaluation occurs 52 weeks after Baseline Assessment (from Day 360 – Day 380). The 
following assessments are performed at the final evaluation. If a participant wishes to terminate the 
study early, this is also the list of assessments we will attempt to complete at termination. Early 
termination will only be done at a participant’s request or if a participant’s risk-to-benefit ratio is 
substantially altered due to a change in status. 
o Conducted remotely through RedCap link sent by e-mail or text to participant 
o Participant-reported questionnaires 

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o Collection of Medical Expense and Opioid use from MDR 
o Collection of Limited Duty days for active duty participants from the MODS 
7. SAFETY ASSESSMENTS  
7.1 Specification of Safety Parameters 
Safety parameters intended to reduce risks for adverse events include having licensed clinicians 
specifically trained in the study procedures carry out all treatments. The potential risk of psychological 
distress from answering self-report questions about the impact of the individual’s chronic LBP on 
various aspects of his or her life will be minimized by allowing participants to leave some items blank if 
they are upsetting and conducting assessments in private rooms.  
7.2 Methods and Timing for Assessing, Recording and Analyzing Safety Parameters 
The risk profile of interventions used in this study is minimal. Treatments in the study are standard 
procedures used in everyday clinical practice and measurement procedures are entirely patient-self 
reported information.  
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of study 
personnel during study follow-up assessments through unsolicited (i.e., without any prompting) means. 
Each follow-up assessment includes a side effects questionnaire that includes the opportunity for 
participants to report adverse events in free-text format beyond the expected side effects of treatments 
provided on the form. Based on the risk status of this project we will not specifically solicit reporting of 
AEs or SAEs during follow-up sessions.  
The occurrence of an AE or SAE may also come to the attention of clinicians providing study treatments 
to participants through unsolicited means. These individuals will be trained in reporting procedures 
(outlined below) on reporting these occurrences to the research team in a timely manner. Based on the 
risk status of this project we will not specifically solicit reporting of AEs or SAEs during study 
treatment sessions.    
7.3 Adverse Events and Serious Adverse Events  
Definitions  
Adverse Event (AE) 
An adverse event (AE) is any untoward medical occurrence in a subject during participation in the 
clinical study or with use of the experimental agent being studied. An adverse finding can include a sign, 
symptom, abnormal assessment (laboratory test value, vital signs, electrocardiogram finding, etc.), or 
any combination of these regardless of relationship to participation in the study. 
Unanticipated Problems (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks 
to subjects or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
• Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the subject population being studied; 
• Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• Suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 

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Serious Adverse Event (SAE) 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• Results in death 
• Is life-threatening (places subject at immediate risk of death from the event as it occurred) 
• Results in inpatient hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant disability or incapacity 
• Results in a congenital anomaly or birth defect   
7.4 
Reporting Procedures 
The site investigator must immediately report to the University of Utah any serious adverse event, 
whether or not considered study related, and must include an assessment of whether there is a reasonable 
possibility that the study caused the event within 72 hours of awareness of the event. Site investigators 
must also report any unanticipated problems within 7 days. The site PI must also report any other 
adverse events, protocol deviations or violations within 7 days of PI awareness. Participating sites must 
submit all reports to their local IRB other entities using the following timeline:   
• Unanticipated problems that are serious adverse events will be reported to the University of Utah 
Data Coordinating Center and IRB, local IRBs, DSMB and NCCIH within 5 business days of the 
investigator becoming aware of the event.  
• Any other unanticipated problem will be reported to the University of Utah Data Coordinating 
Center and IRB, local IRBs, DSMB and NCCIH within 14 days of the investigator becoming aware 
of the problem.   
Should an unanticipated problem need to be reported to the IRB it will be reported to the military IRB 
and University of Utah. A record of all reportable unanticipated problems will be maintained at the 
coordinating site and reported during annual DSM reports. In addition, researchers will record at each 
study visit the occurrence of any other adverse events (e.g., visiting the emergency room or medical 
provider for pain exacerbation, etc.) A report of all adverse events will be maintained by each site and 
reported annually on the DSM report.  
Characteristics of an Adverse Event 
Relationship to Study Intervention 
To assess relationship of an event to study intervention, the following guidelines are used: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the study intervention. 
b. There is a temporal relationship between the intervention and event onset. 
c. The event abates when the intervention is discontinued. 
d. The event reappears upon a re-challenge with the intervention. 
2. Not Related (Unlikely, Not Related) 
a. There is no temporal relationship between the intervention and event onset. 
b. An alternate etiology has been established. 
Expectedness of SAEs 
The Study PI and investigators will be responsible for determining whether an SAE is expected or 
unexpected.  An adverse event will be considered unexpected if the nature, severity, or frequency of the 
event is not consistent with the risk information previously described for the intervention.   
Severity of Event 
The following scale will be used to grade adverse events: 

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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 
7.5 
Follow-up for Adverse Events 
All adverse events will be followed for outcome information until resolution or stabilization. 
7.6 
Safety Monitoring  
The scope and the purpose of this study qualifies as a Phase III clinical trial, therefore a data and safety 
monitoring board (DSMB) will be established based on the NIH guidelines and NCCIH input, and 
commensurate with the level of risk, size, and complexity of this study. At the first DSMB meeting a 
DSM charter document will be finalized.   
 
Composition of the DSMB: The DSMB will consist of at least 5 members appointed by the NCCIH 
and will include at least one member with human subject research monitoring expertise, at least one 
member with relevant disease expertise, at least one member with expertise in the intervention or 
observation technique under study and a biostatistician. DSMB Members must have no financial, 
scientific, or other conflict of interest with the study. 
 
Frequency and Character of DSMB Meetings: Because the study involves procedures with minimal risk, 
we propose to conduct DSMB meetings via conference call on an annual basis. Each DSMB meeting 
will begin with an open session that will be attended by all trial Investigators, Study Coordinators and 
representatives from the NCCIH Program Office. Open session will review study procedures, plans for 
data and safety monitoring, recruitment and retention, gender and minority inclusion, protocol 
adherence, data management, the occurrence of any adverse events. The open session will be followed 
by a closed session that will be attended by only the DSMB members and the NCCIH biostatistician as 
deemed appropriate by the DSMB Chair. The closed session will be used to discuss data to which the 
other Investigators must remain blinded.  
 
Content of DSMB Meeting Reports: DSMB reports from each meeting will review the topics discussed 
at the meeting with respect to study procedures, accrual and retention, data management, etc. The DSM 
report will include a recommendation concerning continuation of the study. Each DSM report will 
provide a tally of all adverse events in each of the categories listed above in all treatment groups.  
Blinding of adverse event results will be maintained and will be broken only if the DSMB indicates a 
need to un-blind groups for serious safety reasons. DSMB reports will be submitted to the Principal 
Investigator, NCCIH Program Office and University of Utah and Military Institutional Review Boards. 
8.   INTERVENTION DISCONTINUATION  
Investigators will only discontinue a participant’s intervention if the risk-benefit ratio for that participant 
changes substantially such that he or she would no longer meet the project’s eligibility criteria. Examples 
include development of signs of neurologic deficit or presentation of “red flag” symptoms suggestive of 
a serious underlying condition. These circumstances will be identified by research personnel during 
study visits for treatment or assessment. If a participant is discontinued we will continue to collect self-
report outcomes only. 
9.  STATISTICAL CONSIDERATIONS  
9.1 General Design Issues  
We will use a SMART study design (fig. 1). The first phase of the design will compare the effectiveness 
of  PT and M2H for treating chronic LBP. Phase I treatment will be 6 weeks in duration with re-

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evaluation at 8-weeks post-enrollment to allow time to initiate and complete treatment. At the 8-week 
assessment we will evaluate if the participant has responded to initial treatment using pragmatic, patient-
centered, definition of a treatment responder. Patients who are responders to Phase I treatment will 
receive up to 2 additional sessions of the same treatment to assist with transition to self-management. 
Non-responders will be re-randomized to a second, Phase II treatment: Either combining the initial 
treatments (PT+M2H) or switching to Mindfulness. Phase II treatment is 8 weeks in duration. Patient-
reported outcomes will be collected again at 18 weeks (post-Phase II treatment), 6 and 12 months after 
enrollment. Direct medical costs and opioid use for LBP care over the 1-year follow-up period will be 
extracted from the MDR database and for active duty participants, limited duty days will be extracted 
from the MODS database at the conclusion of the participant’s time in the study. 
We have incorporated the feedback provided on the study design and biostatistics from the NCCIH 
OCRA and the Study Design Work Group of the PMC Collaboratory. A complete listing of these 
comments and the corresponding responses are provided in Appendix V. 
Our co-primary aims are to compare the effectiveness and cost-effectiveness of Phase I treatments; and 
of Phase II treatments in Phase I non-responders. Our main secondary aim will compare the effective-
ness of each Phase I treatment when followed by Mindfulness or by combined PT+M2H. Exploratory 
aims will compare Phase II treatments separately for each Phase I treatment group, as well as seek to 
identify the 2-stage imbedded treatment regime which provides the optimum average outcome across the 
four 2-stage treatment strategies and evaluate primary and secondary treatment comparisons in pre-
specified sub-groups. Further exploratory analyses will seek to identify the optimum 2-stage treatment 
strategy after accounting for designated characteristics of each patient.  
9.2 Sample Size and Randomization 
Power calculations are based on a conservative estimate of 80% project retention, which we have 
applied across the full follow-up period, and are expressed both as minimum detectable effect sizes for 
80% and 90% power and as statistical power to detect minimum clinically important differences 
(MCIDs) with the planned 850 randomized patients.  All power calculations are based on the guidelines 
for approximating statistical power for SMART trials by Crivello, Levy, and Murphy.176  
The PROMIS-PI and PROMIS-PF result in T-scores with general population means of 50 and SDs of 
10. However, the SDs of the PROMIS-PI and PROMIS-PF have been observed to be somewhat smaller 
in LBP populations similar to the patient population in this study, and we have assumed SDs of 8 points 
for both the PROMIS-PI and -PF. The MCID for the PI- and PF-CAT has been estimated between 2.0 - 
3.5 T-score points for patients with chronic LBP.23,24 We assume the response rate to Phase I treatment 
will fall between 0.30 and 0.45. Also based on data from previous studies, we assume serial correlations 
of R = 0.40 for PROMIS outcomes. We have also considered intra-class correlations (ICCs) ranging 
from 0 to 0.05 to account for clustering of each of the outcomes within the therapists who will carry out 
the mindfulness interventions. We assume the mindfulness intervention will be implemented by 20 
therapists distributed across the 4 sites over the study period. Some level of clustering by therapist is 
also possible for the PT and M2H interventions, but is not incorporated in the power calculations 
because of the likelihood of patients moving between therapists at different treatments and because the 
same therapists will often administer both the PT and M2H interventions. We stipulated a 2-sided α of 
0.05 for the primary PROMIS-PI outcome.  
 
Under these assumptions the minimum detectable effect sizes with 90% power for Aim I comparison of 
PT and M2H groups at 8 weeks are 1.83for the PROMIS-PI and -PF. If ICCs for mindfulness providers 
are assumed to be 0, the minimum detectable effect sizes with 90% power for the Objective II 
comparisons of PT+M2H vs. Mindfulness range from 2.18to 2.46 for the PROMIS-PI and -PF, if Phase 
I response rate ranges from 30% to 45%. If ICCs for the mindfulness therapists are assumed to be 0.05, 
the minimum detectable effect sizes with 90% power for the Objective II comparisons of PT+M2H vs. 

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Mindfulness range from 2.46-2.71, if Phase I response rate ranges from 30% to 45%. All of these 
minimum detectable effect sizes are smaller than the minimum clinically important differences, which 
we have taken to be 2.8 points for the two PROMIS outcomes, which represents 35% of the estimated 
SD of 8 T-score units in our LBP population, and 28% of the SD for the general population. An effect 
size of 35% of 1 SD is considered small to moderate,169 and is highly plausible for the interventions 
being compared. The rationale for selecting a sample size larger than required to detect the MCIDs for 
the two primary objectives is to support subgroup analyses and the analyses of the secondary objectives. 
The supplemental table provides additional power calculations relevant to these secondary analyses.   

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AIM 
 DESCRIPTION  
Assumed SD and Effect Size 
Detectable Effect Size 
Under Varying Assumptions 
Power to detect MCID 
Effect size 
Outcome 
Variable 
Alpha 
Mindfulness 
therapist ICC 
SD 
Outcome  
MCID and 
Effect Size 
30% Phase I 
Response 
Rate 
45% Phase I 
Response 
Rate  
80% 
Power 
90% 
power 
80% 
Power 
90% 
power 
With 30% 
Responder 
Rate 
With 45% 
Responder 
Rate 
1. 
Mean differences in primary outcome between Phase 1 treatments at week 
8 (PT vs. M2H) (Co-Primary) 
PROMIS  PI 
0.05 
- 
8 T-score points 
2.8  
1.58 1.83 1.58 1.83 
0.999 
0.999 
1.i 
Mean differences in secondary outcomes between Phase 1 treatments at 
week 8 (PT vs. M2H)  
PROMIS PF 
0.025 
- 
8 T-score points 
2.8 
1.74 1.98 1.74 1.98 
0.997 
0.997 
Pain 
0.025 
- 
2.2 
2.0 
0.51 0.58 0.51 0.58 
1 
1 
2. 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to either PT or 
M2H (Co-Primary) 
PROMIS  PI 
0.05 
0 
8 T-score points 
2.8 
1.89 2.18 2.13 2.46 
0.986 
0.958 
2.i 
Mean difference in secondary outcomes between Phase II treatments at 6-
mo for non-responders to PT or M2H  
PROMIS PF 
0.025 
0 
8 T-Score points 
2.8  
2.08 2.37 2.34 2.68 
0.972 
0.926 
Pain 
0.025 
0 
2.2 
2.0 
0.61 0.69 0.68 0.78 
1 
1 
2 and 
2.i  
with 
varying 
clinician 
effect 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to either PT or 
M2H (Co-Primary) 
PROMIS  PI 
0.05 
0.025 
8 T-score points 
2.8 
2.01 2.33 2.24 2.59 
0.986 
0.958 
Mean difference in secondary outcomes between Phase II treatments at 6-
mo for non-responders to PT or M2H 
PROMIS PF 
0.025 
0.025 
8 T-Score points 
2.8  
2.21 2.53 2.46 2.81 
0.972 
0.926 
Pain 
0.025 
0.025 
2.2 
2.0 
0.65 0.74 0.72 0.82 
1 
1 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to either PT or 
M2H (Co-Primary) 
PROMIS  PI 
0.05 
0.05 
8 T-score points 
2.8 
2.13 2.46 2.34 2.71 
0.958 
0.918 
Mean difference in secondary outcomes between Phase II treatments at 6-
mo for non-responders to PT or M2H 
PROMIS PF 
0.025 
0.05 
8 T-Score points 
2.8  
2.34 2.68 2.57 2.94 
0.926 
0.867 
Pain 
0.025 
0.05 
2.2 
2.0 
0.68 0.78 0.75 0.86 
1 
1 
2.a 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to PT    
PROMIS  PI 
0.025 
0 
8 T-score points 
2.8 
2.94 3.36 3.32 3.79 
0.756 
0.641 
2.b 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to M2H  
PROMIS  PI 
0.025 
0 
8 T-score points 
2.8 
2.94 3.36 3.32 3.79 
0.756 
0.641 
2.a.i/ 
2.b.i 
Mean difference in secondary outcomes between Phase II treatments at 6-
mo for non-responders to PT (also applies to M2H) 
PROMIS PF 0.0125 
0 
8 T-Score points 
2.8  
3.19 3.61 
3.6 
4.07 
0.668 
0.54 
Pain 
0.0125 
0 
2.2 
2.0 
0.93 1.05 1.05 1.19 
1 
1 
2a/b 
and 
2.a.i/ 
2.b.i 
with 
varying 
clinician 
effect 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to PT    
PROMIS  PI 
0.025 
0.025 
8 T-score points 
2.8 
3.03 3.46 3.39 3.88 
0.728 
0.619 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to M2H  
PROMIS  PI 
0.025 
0.025 
8 T-score points 
2.8 
3.03 3.46 3.39 3.88 
0.728 
0.619 
Mean difference in secondary outcomes between Phase II treatments at 6-
mo for non-responders to PT (also applies to M2H) 
PROMIS PF 0.0125 
0.025 
8 T-Score points 
2.8 
3.29 3.72 3.68 4.16 
0.636 
0.517 
Pain 
0.0125 
0.025 
2.2 
2.0 
0.96 1.09 1.07 1.22 
1 
1 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to PT    
PROMIS  PI 
0.025 
0.05 
8 T-score points 
2.8 
3.12 3.56 3.47 3.96 
0.701 
0.598 

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Power calculations assume 80% retention for each follow-up assessment (this is conservative for the week 8 assessment). We assume serial correlations of R = 0.40 for the PROMIS 
outcomes and 0.23 for the PAIN score. *Calculations performed using statistical simulation are conservative, and apply for all possible response rates.
AIM 
 DESCRIPTION  
Assumed SD and Effect Size 
Detectable Effect Size 
Under Varying Assumptions 
Power to detect MCID 
Effect size 
Outcome 
Variable 
Alpha 
Mindfulness 
therapist ICC 
SD 
Outcome  
MCID and 
Effect Size 
30% Phase I 
Response 
Rate 
45% Phase I 
Response 
Rate  
80% 
Power 
90% 
power 
80% 
Power 
90% 
power 
With 30% 
Responder 
Rate 
With 45% 
Responder 
Rate 
Mean difference in primary outcome between Phase II treatments 
(PT+M2H vs. mindfulness) at 6-mo for non-responders to M2H  
PROMIS  PI 
0.025 
0.05 
8 T-score points 
2.8 
3.12 3.56 3.47 3.96 
0.701 
0.598 
Mean difference in secondary outcomes between Phase II treatments at 6-
mo for non-responders to PT (also applies to M2H) 
PROMIS PF 0.0125 
0.05 
8 T-Score points 
2.8 
3.38 3.82 3.76 4.25 
0.606 
0.496 
Pain 
0.0125 
0.05 
2.2 
2.0 
0.99 1.12 
1.1 
1.24 
1 
1 
3.a 
 Mean difference in primary outcome at 6-mo between Phase I treatments 
with Mindfulness in Phase II (Main Secondary) 
PROMIS  PI 
0.05 
- 
8 T-score points 
2.8 
2.06 2.38 1.96 2.27 
0.968 
0.979 
3.b 
Mean difference in primary outcome at 6-mo between Phase I treatments 
with PT+M2H in Phase II (Main Secondary) 
PROMIS  PI 
0.05 
- 
8 T-score points 
2.8 
2.06 2.38 1.96 2.27 
0.968 
0.979 
3.a.i/ 
3.b.i  
Mean difference in secondary outcomes between Phase I treatments at 6-
mo with Mindfulness in Phase II (also applies to M2H+PT) 
PROMIS PF 
0.025 
- 
8 T-Score points 
2.8 
2.26 2.59 2.16 2.47 
0.942 
0.96 
Pain 
0.025 
- 
2.2 
2.0 
0.66 0.76 0.63 0.72 
1 
1 
V. 
Evaluate aims I-IV in sub-groups of patients based on pre-specified baseline characteristics (age, gender, sleep disturbance, opioid use). Aim V is supported by following sub-aims: 
V.1.i  Mean difference in primary outcome between Phase I treatments at week 
8 in sub-group with 50% prevalence (AIM 1 subgroup analyses) 
PROMIS  PI 
0.05 
- 
8 T-score points 
2.8 
2.23 2.59 2.23 2.59 
0.94 
0.94 
V.1.ii  Mean difference in primary outcome between Phase I treatments at week 
8 in sub-group with 33% prevalence (AIM 1 subgroup analyses) 
PROMIS  PI 
0.05 
- 
8 T-score points 
2.8 
2.74 3.18 2.74 3.18 
0.815 
0.815 
V.2.i 
Mean difference in primary outcome between Phase II treatments at 6-mo 
for non-responders to PT or M2H in sub-group with 50% prevalence (AIM 
2 sub-group analyses) 
PROMIS  PI 
0.05 
0.025 
8 T-score 
points 
2.8 
2.75 3.18 3.08 3.57 
0.813 
0.721 
V.2.ii 
Mean difference in primary outcome between Phase I treatments at 6-mo 
with Mindfulness in phase II (also applies to M2H+PT) in sub-group with 
50% prevalence (AIM 2 subgroup analyses) 
PROMIS  PI 
0.05 
- 
8 T-score 
points 
2.8 
2.91 3.37 2.78 3.22 
0.768 
0.805 

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9.2.1  Handling of Missing Data 
We will record reasons for missing data and attempt to contact lost-to-follow-up patients to determine 
reasons. To assess risk of bias from missing data, patterns of missingness across follow-ups will be 
displayed for all outcomes. We will compare baseline levels of prognostic variables between patients 
with and without missing data. Our longitudinal analyses will either employ maximum likelihood 
estimation under mixed effects models or will be performed using generalized estimating equations 
under generalized linear models, and will be carried out with multiple imputation of missing data.177 
Application of multiple imputation will assure that statistical inference will remain valid in the presence 
of missing data if missingness follows a missing at random (MAR) mechanism94,95. Multiple imputation 
will be carried out using time‐ordered nested conditional imputation models to sequentially impute both 
missing response after phase 1, subsequent treatment assignment and latter outcome variables.178 
Imputation models will include all variables in the analysis and selected additional variables considered 
likely to predict outcome and likelihood of missingness. 
 
The sensitivity of the results to a possible missing not at random (MNAR) mechanism will be 
investigated within the multiple imputation approach by applying an offset term for the mean of the 
missing outcome variable among those patients for whom this outcome is missing, and evaluating the 
dependence of the primary outcome results to varying the size of this offset.181,182 
 
9.2.2   Treatment Assignment Procedures 
Randomization allocation tables will be developed prior to enrollment by the Study Design and 
Biostatistics Center at the University of Utah. Random permuted block randomization with random 
block sizes will be used. Randomization to Phase I treatment will be stratified based on site (TAMC, 
BAMC, MAMC, WHASC), gender and active duty status (yes/no). Randomization to Phase II treatment 
for non-responders will be based on site, gender, active duty status and Phase I treatment group 
assignment. Randomization will be done through the project’s RedCap site using the Randomization 
module. Randomization assignments will be programmed in RedCap by study statistician prior to any 
participant enrollment. 
Based on the pragmatic nature of this project, participants cannot be blinded to study treatments and we 
will not use placebos or attempt to balance clinician time. Randomization assignment will not be 
revealed until baseline assessment is complete to reduce potential bias by either the participant or 
researcher. Follow-up assessments will be performed by a Research Assistant who will be blind to 
participants’ treatment assignments. Clinicians providing treatment cannot be blinded. The use of 
standardized training and guidelines for all treatments and clinician-compliance audits throughout the 
project will permit the opportunity to assess differential treatment application and explore any influence 
on outcomes. The PIs of the project will be able to break the blinding if necessary for participant safety 
considerations. 
9.3  Definition of Populations 
Intention-to-treat principles will be used to guide the data analyses throughout the project with all 
participants analyzed in their randomized group regardless of compliance. We will compare compliance 
between groups and “per-protocol” secondary analyses may be considered if non-compliance is high or 
disproportionate between groups.  
9.4 Interim Analyses and Stopping Rules 
Because of the minimal risk of the procedures in this study, the study does not include formal interim 
analyses for efficacy or futility. The Data Safety and Monitoring Board (DSMB) will monitor the 
occurrence of adverse events throughout the study. If the number of serious adverse events warrants, the 
DSMB may recommend suspension of enrollment and a review the safety of the study procedures. 

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9.5 
Outcomes  
Outcome measure for the primary and secondary hypotheses of the study are outlined below. These 
outcomes will not require adjudication. 
9.5.1   Primary and Secondary Outcomes   
The outcomes used to address the primary and secondary hypotheses of this study are each collected at 
baseline, and at the 8 week, 18 week, 6- and 12-month assessments. We are using use CAT versions 
from the Patient-Reported Outcomes Measurement Information System (PROMIS®) as patient-centered 
assessments of health constructs most relevant to patients with chronic LBP. We are using PROMIS 
CAT measures because they have been developed and validated with rigorous methods123 and assess 
universally-relevant (e.g., physical function, pain interference) instead of disease-specific constructs 
permitting comparisons with different chronic conditions.154 The CAT approach uses item response 
theory to present questions to participants in an adaptive manner based on response to the prior question, 
limiting the number of questions required to reach a robust measure and reducing burden.124   
Primary Outcome: PROMIS Pain Interference CAT (PI-CAT): Computer-adapted assessment using a 
44-item bank measuring the self-reported consequences of pain on relevant aspects of life including 
impact on social, emotional, cognitive, physical and recreational activities. All PROMIS scores are 
reported on a T-score metric with a score of 50 points aligning with the general population mean and a 
standard deviation of 10. Higher scores indicate greater pain interference. 
Main Secondary Outcome: PROMIS Physical Function CAT (PF-CAT): Computer-adapted 
assessment using a 121-item bank measuring current, self-reported capability related to physical 
activities. All PROMIS scores are reported on a T-score metric with a score of 50 points aligning with 
the general population mean and a standard deviation of 10. Higher scores indicate greater physical 
function. 
Additional Exploratory Outcomes and Assessments 
Defense and Veterans Pain Rating Scale (DVPRS): Pain assessment tool utilizing a numeric pain rating 
for pain intensity and four supplemental questions reflecting pain interference with sleep, mood, usual 
activities and stress.159  The numeric rating scale uses a 0-10 rating scale with 0 representing “no pain” 
and 10 representing “pain as bad as it could be, nothing else matters”.  
PEG-3: evaluates pain intensity (P), interference with enjoyment of life (E), and interference with 
general activity (G) in the past week. Each item is assessed on a Likert-type scale 0-10, and individual 
item scores are averaged.162  
PROMIS Sleep Disturbance CAT: evaluates perceptions of sleep quality, depth and restoration 
associated with sleep over the prior 7-day period. 
PROMIS Depression CAT: evaluates negative mood and perceptions of self (e.g., worthlessness), 
diminished positive affect or engagement (e.g., loss of interest in activities) over the prior 7-day period. 
PROMIS Anxiety CAT: evaluates perceptions of fear, worry, dread, hyperarousal (e.g., feelings of 
tension or nervousness, somatic symptoms such as dizziness, palpitations) over the prior 7-day period. 
EuroQol (EQ-5D):155 is a generic quality of life instrument covering the domains of covers 5 domains: 
mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression. Domain scores are 
combined to produce a health state which is commonly used in economic evaluation of clinical trials.156  
Perceived Ability to Return to Duty: Readiness represents the service member’s ability to accomplish 
their mission. The inability to deploy for medical reasons is a significant concern for overall readiness. 
We have used 3 questions in prior studies to assess a service member’s self-perceived ability to perform 
military related tasks (pass a required semi-annual physical fitness test, operate under full combat load, 
and % mission capability).98   

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Treatment Side Effects: We will collect information about side effects participants may experience with 
study interventions. We will ask participants about possible physical (e.g., increased pain or stiffness, 
etc.) and psychological (e.g., increased stress or anxiety, etc.) side effects that they believe resulted from 
study interventions and extent to which they were impacted by the side effect (ranging from “not at all” 
to “extremely”). The questionnaire was developed from existing side effect questionnaires used in 
studies of physical and psychological interventions for individuals with chronic pain.138,139 
Limited Duty Days: (active duty only): We will extract information about limited duty days for participants on 
active duty across the entire 1-year surveillance follow-up period. This information is stored in eProfile, a 
software application within the Medical Operational Data System (MODS) that allows global tracking of type, 
reason, and length of limited duty days related to medical conditions. 
Long-Term Opioid Use: The pharmacy data transaction service (PDTS) file of the MDR captures all 
medication prescriptions that occur inside the MHS and outside when covered by Tricare. Unique 
number of prescriptions with therapeutic class codes that represent opioid-based pain medication 
(280808, 280812) and total days’ supply will be calculated for each patient over the course of the 1-year 
follow-up. We will also calculate daily opioid dose at each follow-up point based on dose of opioids at 
that time converted to a morphine milligram-equivalent (MME) dosages by multiplying daily dose of a 
given opioid by published conversion factors.161 We will define long-term opioid use at each follow-up 
based on the number of opioid fills recorded, the days’ supply for each fill and the morphine milligram 
equivalents (MME) for each fill. Long-term opioid use will be defined as > 90 days of continuous opioid 
use in the preceding 180-day period. As a sensitivity analysis we will also define long-term opioid use as 
≥ 120 days or > 90 days with 10 or more fills during the 1-year follow-up period. 
Direct Medical Expenses: We will use the MDR to identify total healthcare costs and LBP-related 
healthcare costs over the 1-year follow-up period. The MDR contains Tricare claims for all inpatient and 
outpatient medical encounters in any setting (military or civilian network). Each encounter is assigned a 
cost based on RVUs to represent the cost associated with delivering the care. RVU-based costs allow 
comparisons on the aggregate level and in specific categories (i.e., medication, inpatient costs, 
ambulatory care, etc.). We will apply adjustment procedures to account for medical inflation across 
different years of data collection as needed when evaluating costs and conducting cost-effectiveness 
analyses. MDR data also contains billing codes which allow for identification of specific utilization 
outcomes during the follow-up period including lumbar MRI, CT scan, fluoroscopically-guided 
injections and surgical procedures. 
9.6 
Data Analyses  
Analyses will be carried out by the Study Design and Biostatistics Center, the biostatistics core of the 
University of Utah CCTS. We will monitor data quality and completeness during the study so 
discrepancies can be resolved in real time. Intention-to-treat principles will be used to guide the data 
analyses throughout the project with patients evaluated based on randomized assignment regardless of 
compliance. Skewed outcomes may be transformed to approximate normality. Analyses for each aim of 
the project are outlined below. 
Aim I: This co-primary aim compares the effectiveness of Phase I treatments (M2H or PT) on the 
primary outcome (PI-CAT) at 8 weeks follow-up. Because the outcome is evaluated prior to the Phase II 
treatment, the primary analyses of Aim I conform to a standard 2-group comparison without the 
complications of a 2-phase design. The primary Aim I analysis will be carried out by fitting a 
longitudinal linear mixed model for the baseline and 8-week PI-CAT, using an unstructured covariance 
matrix to account for serial correlation between the two measures, and imposing the constraint that the 
baseline means for the PI-CAT are equal in the Phase I treatment groups. This model, sometimes 
referred to as a constrained longitudinal model leads to adjustment for baseline levels as in analysis of 
covariance (ANCOVA), which has been shown to remove conditional bias in treatment group 
comparisons due to chance imbalances and improve statistical power over unadjusted comparisons.179 

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By using an unstructured covariance matrix, the model will constitute a special case of a general linear 
mixed model which avoids imposing specific assumptions concerning distribution of random effects. 
Restricted maximum likelihood estimation will be used for estimation of the mean adjusted difference in 
the 8-week PI-CAT between the M2H and PT treatment groups and to provide confidence intervals and 
hypothesis tests. The same approach will be used to compare the PROMIS-PF between Phase I 
treatment groups. In this analysis as well in other longitudinal analyses described below, clinical center 
and the sex and active duty status randomization stratification factors will be included as covariates.  
Aim Ii: This sub-aim compares secondary outcomes (pain intensity, sleep, depression, anxiety) between 
PT and M2H using a similar longitudinal linear model to that described above. We will use generalized 
estimating equations86 to relate Phase I treatment to binary indicator variables for long-term opiod use 
during successive intervals across the 1-year follow-up under a generalized linear model for binary 
outcomes. GEE analyses will use robust standard errors for statistical inference. Hypothesis tests for the 
single primary outcome and for secondary outcomes will be performed on a comparison-wise basis 
without adjustment for multple comparisons.87 
Aim II: This co-primary aim compares the effectiveness of Phase II treatments (Mindfulness or 
M2H+PT) in Phase I non-responders, by fitting a longitudinal linear  mixed effects model to relate the 
randomized Phase II treatments to the PI-CAT primary outcome measures at 18 weeks, 6 and 12 
months, with the 8-week outcome level included as a covariate to account for the effects of Phase I 
treatment and serve as the baseline for comparing Phase II treatments. The model will include random 
effects for the therapists of the mindfulness intervention for those patients who are randomized to the 
mindfulness intervention. As stated above, clinical site, sex, and active duty status will be included as 
covariates as will Phase I treatment group. These analyses will be restricted to the subcohort of patients 
who fail to respond to the Phase I treatment and who remain in follow-up sufficiently long to be 
randomized to the Phase II treatment. The primary treatment contrast will compare the 12-month PI-
CAT between the two Phase II interventions among all Phase I non-responders, while averaging over the 
Phase I treatments.  
Aims IIa and IIb. In exploratory analyses, the longitudinal mixed model of Aim II will be fit separately 
to nonresponders of the PT intervention and to nonresponders to the M2H intervetention; these analyses 
will compare the effectiveness of the Phase II treatments separately for non-responders to each of the 
Phase I treatments. A Bonferroni correction will be applied to these latter analyses to account for 
separate comparisons in the non-responders to each of the Phase I interventions.  
Aim IIIa and IIIb: These aims compare the effectiveness of Phase I treatments contingent on the Phase II 
treatment. Aim IIIa analyses will be performed in randomized patients who respond to their Phase I 
treatment or who do not respond and are randomized to Mindfulness in Phase II, and will compare  two 
dynamic treatment regimens imbedded within the SMART design: Treatment with M2H followed by 
mindfulness in nonresponders to M2H vs. PT followed by mindfulness in nonresponders to PT. The 
principal analysis for Aim IIIa, which is also designated as the main secondary analysis for the study, 
will apply weighted estimating equations with robust standard errors designed for analysis of 
longitudinal outcomes in SMART trials180 to compare the PI-CAT at weeks 8 and 18 and months 6 and 
12 between the patients initially randomized to PT or M2H in Phase I, with covariate adjustment for the 
baseline level of the outcome. Site, sex, and active duty status will again be included as covariates. The 
12-month assessment will again serve as the primary comparison. Inverse probabilty of treatment 
weighting will account for nonresponders being re-randomized and thus split in two groups and 
underrepresented relative to responders. We note the Phase I treatment in an optimal 2-stage sequence 
may differ from the Phase I treatment optimzing outcome at the end of Phase I (Aim 1). For example, 
M2H may be superior to PT following Phase I, but a sequence of PT followed by Mindfulness may be 

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the preferred 2-stage sequence. The longitudinal analyses will be adapted analogously to those of Aim 1 
to estimate the effects of the Phase I treatments followed by Mindfulness on secondary outcomes. 
Analyses for aim IIIb will be performed in randomized patients who respond to their Phase I treatment 
or who do not respond and are then randomized to PT+M2H in Phase II. Analyses for aim IIIb will be 
analogous to those of aim IIIa, and will address if the order in which PT and M2H are administered 
matters when applying these interventions sequentially. 
Aim IV:  The analyses of Aim IV will compare four embedded 2-stage strategies: a) PT followed by 
M2H+PT in non-responders, b) PT followed by Mindfulness in non-responders, c) M2H followed by 
M2H+PT in non-responders, and d) M2H followed by Mindfulness in non-responders. The analyses will 
apply weighted estimating equations with robust standard errors appropriate for analysis of longitudinal 
outcomes in SMART designs while accounting for clusting by mindfulness therapists to estimate the 
mean PI-CAT for all four 2-stage strategies at weeks 8 and 18, and months 6 and 12.180 The dataset will 
be augmented by including each patient either once or twice depending on whether the patient’s 
treatment is consisent with one or two 2-stage strategies164,166  (e.g., the treatment sequence of a patient 
who responds to PT in Phase I is consistent with both regimens a and b above). As in Aims IIIa and IIIb, 
we will employ inverse probabilty weighting to account for nonresponders being re-randomized and 
thus split in two groups and underrepresented relative to responders.  
Aim V: The analyses of Aim V will evaluate specific aims I-IV within sub-groups of patients defined by 
key baseline characteristics (gender, age, sleep disturbance, and baseline opioid use). Specifically, we 
will examine sub-groups based on gender (male or female), age (using a threshold value of >50 years 
old at baseline), sleep disturbance (using a threshold value of >50 on PROMIS Sleep Disturbance CAT 
at baseline) and baseline opioid use (using a threshold of regular opioid use for at least 1 month). 
For aims I-III, sub-group analyses will be performed by repeating the longitudinal analyses within each 
pre-specified subgroup, and by extending the statistical models by adding interactions between treatment 
and the subgroup factors. We will display forest plots of estimated treatment effects within each 
subgroup with p-values for the treatment by subgroup factor interactions indicated on the plots. Results 
of subgroup analyses will be assessed primarily based on the treatment by subgroup interactions, using 
2-sided α = 0.05 for the primary outcome, PI-CAT, without adjustment for multiple sub-groups. 
Sub-group analyses for aim IV will use Q-learning methods to investigate the more complex treatment 
strategies  to estimate an optimal intervention in which Phase I and II treatments are tailored to patient 
sub-group characteristics. We have designated PI-CAT at 1-year as the primary outcome for the Q-
learning procedure. We will implement Q-learning39 by defining subject data as O1, A1, O2, A2. O1 
designates patient subgroup factors available prior to the Phase I (gender, age and pain-related co-
morbidities); A1 is Phase I treatment (PT, M2H); O2 is response to Phase I treatment (responder, non-
responder); and A2 is Phase II treatment for non-responders (PT+M2H, mindfulness). Q-learning uses 
two regression models corresponding to the two treatment Phases to determine the optimal sequence 
where the selection of Phase I treatment (A1) takes into account subgroup factors (O1), and Phase II 
treatment (A2) takes into account subgroup factors (O1), Phase I treatment (A2) and response to Phase I 
(O2). The Phase I regression model incorporates the interaction between O1 and A1, and the Phase II 
model includes interactions of O1 with A1, A1 with A2, and O2 with A2 to account for heterogeneity of 
Phase I and II treatment effects. The optimized 2-stage sequence depends on the regression coefficients 
for the models corresponding to the two Phases. Statistical inference will be performed using soft-
thresholding40 or the m-out-of-n bootstrap.41 The ultimate result of the analysis will be an estimate of the 
optimal 2-stage treatment sequence for each combination of values for the patient subgroup factors.  

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10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1 
Data Collection Forms  
Participant-reported measures will be collected via an electronic data capture system; either REDCap or 
MOTION. REDcap (Research Electronic Data Capture) is an NIH-supported, browser-based platform 
that allows researchers to create secure online forms for data capture, management and analysis. At each 
assessment participants can input data directly into REDCap. If a participant is unable to directly input 
data, paper forms will be available with data uploaded at a later time. MOTION (Military Orthopaedics 
Tracking Injuries and Outcomes Network) is an initiative of the Rehabilitation and Reintegration 
Division (R2D) of the Army Office of the Surgeon General. MOTION is a web-based application for 
collecting patient-reported outcomes that allows patients to input information from any internet-enabled 
device. MOTION may capture the same study-related measures. To avoid additional participant burden 
scores from MOTION will be entered into REDCap in these circumstances. 
A research assistant blinded to the participant’s randomly-assigned treatment group will conduct the 
assessments to avoid bias. The baseline, 8- and 18-week assessments will be done in-person with a 
research assistant blinded to the participant’s treatment group. The 26- and 52-week follow-ups will be 
conducted electronically without an in-person meeting with a member of the research team, who will be 
blinded to the participants’ treatment group. These follow-up assessments will collect outcomes data 
either through MOTION or REDCap, whichever is easier to access for the participant. 
Additional participant data will be administratively collected from the Military Health System Data 
Repository (MDR). The MDR is a comprehensive source of data containing records on every person-
level interaction for healthcare where Tricare is the payer regardless of setting, capturing direct care 
provided in military facilities and purchased care provided in civilian settings.122 The MDR incorporates 
historical and demographic beneficiary and coverage data as well as clinical and ancillary care data 
including pharmacy (prescription, medication type and dosage), radiology, etc. The MDR links claims 
and demographic data to provide detailed information on co-morbidities, health care utilization and 
financial data for all service members, retirees and dependents registered in the Defense Enrollment 
Eligibility Reporting System (DEERS) and eligible for Tricare benefits.  
This project will extract data from the MDR for each participant over a 24-month period – 12 months 
prior to and after enrollment. This will allow us to derive a co-morbidity profile for each participant. The 
MDR Pharmacy Data Transaction Service file captures all medication prescriptions that occur in either 
military or civilian settings. The unique number of prescriptions with therapeutic class codes as well as 
total days supply are available. Of particular interest for this project are opiate-based pain medication 
(AHSF codes 280808, 280812), which is a study outcome.  
Each enrolled subject will receive a site-specific unique Subject Identifier generated prior to enrollment 
that will be used to de-identify the final study dataset. As a preliminary step required to merge 
participant-reported and MDR data, an extraction that uses each subject’s DoD Identifier is required. 
This merge will be completed internally on a secured and encrypted government computer. A list 
containing the DoD Identifier numbers, de-identified Subject Identifier and enrollment date for each 
subject will be sent to the Program Analysis and Evaluation Division (PA&E) of US Army Medical 
Command after the Data Sharing Agreement has been approved and signed by the Data Privacy Board 
of the U.S. Defense Health Agency. The PA&E analyst will extract healthcare utilization for the 12 
months prior and 12 months after enrollment utilizing the DoD Identifier number. After data are merged 
the DoD Identifier number will be removed, leaving only the de-identified unique Subject Identifier on 
the record. The de-identified dataset will be provided to a member of the DoD research team. At this 
point, the dataset will be fully de-identified, with all 18 HIPAA identifiers removed.  

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De-identified datasets will be encrypted and password protected before transfer to the University of Utah 
SDBC. The preferred method for secure data transfer by the Department of Defense is through the 
AMRDEC SAFE (SAfe File Exchange) program developed by the U.S. Army Aviation and Missile 
Research Development and Engineering Center (https://safe.amrdec.army.mil/).  Data can be transferred 
electronically through the use of this encrypted online system, with maximum file sizes of 2GB. 
Linkages of the Subject Identifier and DoD Identifier will not be transferred to the SDBC but will be 
maintained by the DoD in an encrypted file, on a password-protected and encrypted military computer. 
Any participant information collected through REDCap will use the Subject Identifier and linkage with 
the DoD identifier is not necessary in order to merge these data. 
 
10.2 
Data Management  
Clinical sites participating in this project will be responsible for collecting electronic data from 
participants. Any source documents not stored electronically will be maintained in locked cabinets 
within the personal offices of the PI or study coordinator at each site. Any electronic documents outside 
of MDR, REDCap or MOTION, as well as any data output from MDR, REDCap or MOTION, will be 
kept in an encrypted file, on a password-protected and encrypted computers maintained by a member of 
the research team. Based on responsibility delegation by Military Institutional Review Boards, the local 
site PI will be responsible for security and confidentiality at each performance site. 
The University of Utah SDBC will be responsible for maintaining and analyzing the project database. 
The database will be kept on a server supplied by University of Utah Health (UUH). The UUH utilizes 
technology from Hitachi Data Systems called the Universal Storage Platform for providing a virtualized 
storage area network. This network is maintained on a server by University of Utah Health Information 
Technology Services. All programming for the analyses are also stored on the same server and 
coordinated through the University of Utah SDBC. 
Transfer of patient-identifiable information for research involving the DHA and University of Utah will 
be governed by a Data Sharing Agreement (DSA). All data exchanged under the DSA falls under the 
Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, implemented at 45 C.F.R., 
Parts 160 and 164, and the Privacy Act of 1974, as amended, 5 U.S.C. 522a. Data transmission and 
storage data exchanged between the DHA and the University of Utah will be in compliance with HIPAA 
security and privacy provisions. All data use will be governed by the DSA and IRB oversight at the 
University of Utah. All electronic communication between investigators and performance sites that 
contains data for analysis will be transmitted in compliance with the Office of the Surgeon General/ 
MEDCOM Memorandum “Security of Electronic Mail (email) Containing Protected Health Information 
(ePHI).” All datasets will be de-identified with no PHI/PII included.  
10.3 
Quality Assurance  
10.3.1   Training 
Project investigators will conduct training sessions for all research assistants and clinicians who will 
provide study interventions. Investigators from the University of Utah and Department of Defense will 
train providers at each participating site. Training will consist of in-person, didactic instructions, written 
instructions for the performance of study-related techniques and hands-on practice as appropriate. 
Clinicians will receive additional training in all study-related treatment procedures previously described. 
Training goals will be accomplished by providing theoretical and practical information related to this 
project and the procedures employed. Management strategies based on group assignment will be 
highlighted with case examples. All clinicians and research personnel must complete training before 
participating in any study-related procedures. A training log will record successful completion of 
training activities. Both Principal Investigators are experienced in training clinicians to successfully 
perform research-related treatment procedures, and researcher personnel in collection of human subjects 

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data. All personnel will be trained for their role in the project before enrollment begins. Detailed Study 
Protocols for each intervention will be compiled under the supervision of the PIs with input from all 
investigators as described in section 5 of this document. All study personnel will review and familiarize 
themselves with the Study Protocols in detail prior to participation. 
10.3.2   Quality Control Committee 
Quality control for study data will be monitored and overseen by the University of Utah SDBC, the Data 
Coordinating Center for the project. The SDBC is overseen by Dr. Tom Greene with support from Dr. 
Jincheng Shen and study statistician Molly McFadden. Quality control for data merged into the study 
database from the MDR is monitored through the Program Analysis and Evaluation Division at the US 
Army Medical Command overseen by Mr. Richard Thorp. 
10.3.3   Metrics 
Quality metrics for study-related participant data include counts and percentages of missing or 
incomplete responses and protocol deviations. These metrics will be reported at least annually on DSMB 
reports for open and closed sessions. Quality metrics for study-related treatment data will examine the 
number of intervention sessions completed by randomized group. Goals for compliance include 
initiating the study intervention and for each intervention session obtaining > 90% compliance with 
receiving the intervention’s core components. The SDBC Quality Control Committee will generate 
monthly reports of recruitment, retention, quality metrics for treatment compliance with core 
competencies, treatment attendance and protocol deviations across all sites. The format of monthly 
reports will be similar to open session reports prepared for the DSMB. Monthly reports will be reviewed 
by the investigator team and research staff at each site.     
10.3.4   Protocol Deviations 
All protocol deviations and adverse events will be recorded at each study site as outlined in Section 7. 
Deviations or adverse events will be reported in a timely manner to the site and project PIs and to the 
IRBs of the participating institutions as required. Annually, a report will be compiled for review by the 
DSMB and NCCIH representatives. The DSMB may request more frequent reviews if necessary. 
10.3.5   Monitoring 
Protocol deviations are monitored at each project site and are overseen by the site PI. Protocol 
deviations will be reported to the University of Utah as the Coordinating Center from each site PI. As 
specified in Section 7, any protocol deviation that is also an adverse event (e.g., incorrect randomization, 
failure to obtain informed consent, etc.) will be reported to the site and central IRB as well as the DSMB 
and NCCIH within 7 days of awareness. Protocol deviation that do not qualify as adverse events 
(assessments occurring outside the specified time window, participants receiving prohibited 
interventions, etc.) will be reported to the University of Utah from each site PI in quarterly monitoring 
reports. A report of all protocol deviations occurring across study sites will be maintained by the 
University of Utah and reported annually on the DSMB report.  
We have developed the study procedures to minimize data quality concerns. Study data is be collected 
using the REDCap or MOTION platforms. These platforms include functionality that limits data ranges 
and types, thus reducing the chance for input of out-of-range values or incomplete responses. 
Restrictions available within REDCap also provide identification verification through login and 
passwords, required field verification and prevent duplicate records to minimize the chance for data 
input errors. In addition to passing point-of-entry edits, all study data entered to the central study 
database will be subjected to extensive monitoring procedures on a routine basis by the SDBC. The 
SDBC will internally review distributions of baseline and follow-up variables to detect extreme values 
or inconsistent results and will notify the PI if problematic data are detected. 

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11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 
Institutional Review Board (IRB) Review  
This protocol and the informed consent documents from each study site and any subsequent 
modifications will be reviewed and approved by the IRB or ethics committee responsible for oversight 
of the study.  
11.2 
Informed Consent Forms 
A signed consent form will be obtained from each participant. For participants who cannot consent for 
themselves, such as those with a legal guardian (e.g., person with power of attorney), this individual 
must sign the consent form. The consent form describes the purpose of the study, the procedures to be 
followed, and the risks and benefits of participation. A copy will be given to each participant or legal 
guardian and this fact will be documented in the participant’s study record.  
11.3 
Participant Confidentiality  
Participant confidentiality will be protected in the data collection process. All personnel involved with 
the research at both sites responsible for collecting and handling the data will have completed the 
Collaborative Institutional Training Institute (CITI) modules for Human Subjects Research and 
Responsible Conduct of Research. Approval will be obtained by the respective Institutional Review 
Boards. Consent forms that identify the patient by name will be stored in a locked cabinet by the site 
Investigators. All data are assigned a unique identifier (not containing PHI) to identify each participant 
in the study database. Participants will be instructed not to identify themselves by name on any 
instrument. The data file linking names and code numbers will be accessible only to the site PI or 
Coordinator, and data will be entered into study databases by this unique identifier. If data are used in 
scholarly presentations or journal articles, the investigators will protect the anonymity of individual 
participants and will report only aggregate data where appropriate. No audio or video taping will be 
conducted as part of this study. Information will not be released without written permission of the 
participant, except as necessary for monitoring by IRBs, NCCIH, and the OHRP. 
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 
This project is guided by a governance plan designed to facilitate decision-making and assist with 
resolving any disputes that may arise. The governance plan encompasses a committee structure that is 
designed to align with the NIH-DoD-VA Collaboratory Committee structure. The project has two 
Principal Investigators; Drs. Fritz and Rhon. Dr. Rhon is the content expert for engagement of military 
treatment facilities, oversight of DoD regulatory compliance and treatment implementation within 
military facilities. Dr. Fritz serves as the content expert for data management processes and procedures 
including data analysis and quality assurance. Drs. Fritz and Rhon talk via phone at least bi-monthly to 
discuss project management. More frequent meetings occur as circumstances dictate. In addition, the PIs 
will meet at least quarterly with the investigator team by conference call or in-person. Both PIs are 
members of the NIH-DoD-VA Collaboratory Steering Committee.  
Drs. Fritz and Rhon guide overall execution of the project. They are responsible for assuring regulatory 
compliance, conducting the project using high ethical standards and completing all close-out and 
intellectual property requirements. Each PI is responsible for fiscal management of the project within 
their institution. Resource allocation will be based on the priorities of the project aims. The scientific 
direction of the proposal will be determined by both PIs in conjunction with the NIH-DoD-VA Pain 
Management Collaboratory. Members of the investigator team serve on Collaboratory Work Groups as 

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outlined below. Team members report on decisions from the Collaboratory Work Groups at investigator 
meeting. If new directions or opportunities present, these are discussed and prioritized by the 
investigator team. Every attempt to reach consensus among the team will be attempted. If consensus 
cannot be reached on decisions related to scientific direction and resource allocation, a vote of the 
investigator team will be taken. 
The Project Steering Committee will serve as the operational group responsible for coordination of the 
activities of the project team centers and interactions with the NIH-DoD-VA Pain Management 
Collaboratory. The Steering Committee will identify scientific and policy issues that need to be 
addressed throughout the Project, develop recommendations to the NIH Project Team for addressing 
such issues, coordinate the primary recommendations for assay distribution within the Network, and 
coordinate the dissemination of screening data, assay protocols, and other materials with the wider 
scientific community. The Steering Committee membership will include the two project PIs (Drs. Rhon 
and Fritz), Dr. Greene, Director of the SDBC, the NIH Scientific Program Manager (Dr. Mudd), Science 
Officer (Dr. Matocha) and Program Official (Dr. Clark). 
Tasks of the Steering Committee Include: 
1) Convene at least twice yearly by conference call. The purpose of these meetings will be to assess 
scientific progress, identify any difficulties or obstacles and discuss strategies. 
2) Consider and respond to recommendations and policies from the NIH-DoD-VA Pain Management 
Collaboratory. 
3) Identify additional research opportunities. 
4) Evaluate efforts towards dissemination of project findings, research tools and products. 
The Responsibilities of the Research Team Members of the Steering Committee include: 
• Establish agenda and schedule Steering Committee meetings 
• Submit data and progress reports related to recruitment, retention, quality metrics and analysis and 
interpretation of results 
• Present ongoing information on Project progress relative to milestones 
• Identify potential challenges or obstacles and work with NIH Project Team Members towards 
resolution. 
• Abide by policies and procedures related to data sharing, publications and presentations in 
consultation with NIH Project Team Members 
The Responsibilities of the NIH Team Members of the Steering Committee include: 
• 
Provide relevant scientific expertise and overall knowledge.  
• 
Assist in the integration of the Project into the broader objectives and goals of the Pain 
Management Collaboratory   
• 
Participate with the other Steering Committee members in the group process of setting research 
priorities and the adjustment of research protocols or approaches as warranted.  
• 
Work with the other Steering Committee members to ensure Project objectives and milestones 
are being met. 
 
 

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13.  COVID-19 STUDY IMPACT 
13.1  Timeline of COVID-19 Impact and Activities 
March 19, 2020:  the Regional Health Command - central IRB at Brooke Army Medical Center 
announced that all research activity with human participants that was non-essential and non-critical were 
suspended until further notice. All participant screening and enrollment was suspended beginning March 
19, 2020 in compliance with this policy. 
 
March 19, 2020:  The COVID-19 pandemic and resulting mitigation policies resulted in a partial 
suspension of the clinical trial. Partial suspension indicates that all new enrollment was suspended 
across all Military Treatment Facilities participating in the project. Additional details of the partial 
suspension included: 
a) Intervention Delivery: Disruptions in clinical services at participating Military Treatment Facilities 
disrupted the ability to provide care to individuals who were enrolled in the trial. The study team 
advised site research personnel to provide services as possible for participants who were randomized 
into a treatment group at the time of the disruption. No participants are being re-randomized to a 
Phase II treatment if they were in Phase I at the time of the disruption. 
b) Participant Follow-Up / Outcomes Assessment: Follow-up assessments are conducted remotely 
through Redcap for enrolled participants using the timeframes for assessment specified in our 
protocol. As noted previously, no participants are being re-randomized into a new Phase II treatment 
if they are determined to be a non-responder at the first follow-up. 
March 30, 2020:  The study team had a conference call with the Study Design Working Group of the 
PMC. There was agreement that providing treatments via telehealth is not the intent of the study. 
Although the exact procedures that will be used to handle the data from the 32 enrolled participants were 
not determined at this time; it was decided that the team would not seek protocol or informed consent 
amendments to permit telehealth to be substituted as an alternative to the in-person protocols in the 
study. The provision of telehealth to patients in the midst of receiving care at the time of disruption is 
considered consistent with the commitment to these individuals, and not a study intervention.  
May 11, 2020:  The study team met with the Data and Safety Monitoring Board. The report of the 
DSMB to the study team supported the suspension of enrollment, continued remote follow-up per the 
current protocol. The DSMB recommended inclusion of COVID-19 survey to collect data on the impact 
of the pandemic on trial participants.  
13.2  Data Management Considerations in Response to COVID-19 Disruptions 
The participants who were enrolled in the trial at the time of the partial suspension (March 17, 2020) 
will continue to receive follow-up assessments using the assessment timeframes identified in the study 
protocol. 
The study team will document the impact of COVID-19 disruptions on these participants including 
inability to access assigned treatments, completion of treatment visits using remote delivery instead of 
in-person, inability to transition to Phase II treatment per the study protocol, etc. These disruptions will 
be recorded as protocol deviations.  

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Protocol deviations will be provided in subsequent DSMB reports. Prior to finalizing the study database, 
the study team in consultation with the DSMB and NIH personnel will address any relevant statistical 
impacts due to protocol deviations and recommend any amendments to the statistical analysis plan. 
 
 
 
 
 

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MHS/DoD Research 
Team Members 
 
NIH-DoD-VA Collaboratory 
Work Group Members 
 
University of Utah 
Research Team Members 
 
Lt. Col Ben Hando, DSc, 
WHASC Site Lead, Air 
Force Representative  
Major Chris Kenney, DO, 
CRDAMC Site Lead 
Col Deydre Teyhen, PhD, 
Move to Health Lead  
Mr. Richard Thorp, MS 
MDR Analyst, Informatics 
Lead 
Lt Col Ian Lee, DSc, 
MOTION Lead 
Dr. Ben Keizer, PhD, Pain 
Psychology Consultant 
Tom Greene, PhD, Study 
Design and Biostatistics 
 
Jacob Kean, PhD, Data 
Management / Sharing  
Eric Garland, PhD, MORE 
Mindfulness Lead 
Jaewhan Kim, PhD, 
Health Economics 
Megan Vanneman, PhD, 
Informatics and Health 
System Innovation 
MHS Study Site Personnel 
Wilford Hall Ambulatory Surgery Center 
Site PI: MAJ Jeremiah Sampson 
Research Coordinator: Tina Greenlee 
Director, Primary Care: COL Karen Bowman 
Madigan Army Medical Center  
Site PI: MAJ Brian Hatler 
Research Coordinator: Rachel Mayhew 
Director, Department of Family Medicine: 
COL Robert Oh 
Brooke Army Medical Center 
Site PI: MAJ Chris Allen 
Research Coordinator: Mary Laugesen 
Director, Department of Family and 
Community Medicine: LTC Timothy Switaj 
 
Stakeholder 
Dr. Deydre Teyhen 
Design/Biostatistics  
Dr. Tom Greene 
Dr. Jincheng Shen 
Ethics/Regulatory  
Dr. Dan Rhon 
EHR  
Dr. Ian Lee 
Dr. Megan Vanneman 
Outcomes/Phenotypes 
Dr. Julie Fritz 
Data Sharing  
Dr. Jacob Kean 
Mr. Richard Thorp 
Principal Investigators 
Julie Fritz, PhD Professor, University of Utah  
Major (Ret) Dan Rhon, DSc, U.S. Army Surgeon General Office 
Jincheng Shen, PhD, 
Study Design and 
Biostatistics 
NIH Personnel 
Dr. Lanay Mudd, PhD, NCCIH Program 
Director 
Dr. Dave Clark, NCCIH Program Director 
Dr. Martha Matocha, PhD, NINR Team Lead, 
Symptom Science and Genetics 
PMC3 Coordination Center 
Drs. Robert Kerns, Peter Perduzzi and 
Cynthia Brandt PIs 
Steering Committee (Dr. Kerns Chair) 
PMC Operations Core Work Groups 
Project Steering Committee 
Drs. Fritz, Rhon and Greene from Research Team 
Drs. Mudd, Clark and Matocha from NIH 

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APPENDIX I 
 
Literature Cited 
 
 

 
1. Kerns RD, Philip EJ, Lee AW, Rosenberger PH. Implementation of the veterans health 
administration national pain management strategy. Trans Behav Med. 2011;1:635-43. 
2. Vallerand AH, Cosler P, Henningfield JE, Galassini P. Pain management strategies and lessons 
from the military: a narrative review. Pain Res Manag. 2015;20:261-8. 
3. Institute of Medicine. Committee on Advancing Pain Research. Relieving Pain in America: a 
Blueprint for Transforming Prevention, Care, Education and Research. Washington, DC: 
National Academies Press; 2011. 
4. Clark LL, Taubman SB. Brief report: Incidence of diagnoses using ICD-9 codes specifying 
chronic pain (not neoplasm related) in the primary diagnostic position, active component, U.S. 
Armed Forces, 2007-2014. MSMR. 2015;22:12-16. 
5. Toblin RL, Quartana PJ, Riviere LA, Walper K, Hoge CW. Chronic pain and opioid use in US 
soldiers after combat deployment. JAMA Int Med. 2014;174:1400-1. 
6. Office of the Army Surgeon General. Pain Management Task Force. Providing a Standardized 
DoD and VHA Vision and Approach to Pain Management to Optimize the Care for Warriors 
and Their Families. Final Report.  May, 2010. http://www.regenesisbio.com/ 
pdfs/journal/pain_management_task_force_report .pdf . Accessed January 12, 2017. 
7. Licciardone JC. The epidemiology and medical management of low back pain during 
ambulatory medical visits in the United States. Osteopath Med Primary Care. 2008;2:11. 
8. Dieleman JL, Baral R, Birger M, et al. U.S. spending on personal health care and public health 
1996-2013. JAMA. 2016;316:2627-46. 
9. Cohen SP, Gallagher RM, Davis SA, Griffith SR, Carragee EJ. Spine-area pain in military 
personnel: review of epidemiology, etiology, diagnosis, and treatment. Spine J. 2012;12:833-42. 
10. Clark LL, Hu Z. Diagnoses of low back pain, active component, U.S. Armed Forces, 2010-
2014. MSMR. 2015;22:8-11. 
11. Cohen SP, Nguyen C, Kapoor SG, et al. Back pain during war: an analysis of factors affecting 
outcome. Arch Intern Med. 2009;169:1916-23. 
12. Cleeland CS, Reyes-Gibby CC, Schall M, et al. Rapid improvement in pain management: The 
Veterans Health Administration and the Institute for Healthcare Improvement Collaborative. 
Clin J Pain. 2003;19:298-305. 
13. Chou R, Deyo R, Friedly J, et al. Noninvasive Treatments for Low Back Pain. Comparative 
Effectiveness Review No. 169. (Prepared by the Pacific Northwest Evidence-based Practice 
Center under Contract No. 290-2012-00014-I.). Rockville, MD: Agency for Healthcare 
Research and Quality; February 2016. 
14. Childs JD, Fritz JM, Wu SS, et al. Implications of early and guideline adherent physical 
therapy for low back pain on utilization and costs. BMC Health Serv Res. 2015;15:150. 
15. Office of the Secretary of Defense. Report to the Armed Services Committee of the Senate and 
the House of Representatives: The Implementation of a Comprehensive Policy on Pain 
Management by the Military Health Care System for Fiscal Year 2016. November 2016. 
http://www.health.mil/Reference-Center/ Reports/2016/11/16/Comprehensive-Policy-on-Pain-
Management. Accessed January 12, 2017. 
16. Reyes-Guzman CM, Bray RM, Forman-Hoffman VL, Williams J. Overweight and obesity 
trends among active duty military personnel. Am J Prev Med. 2015;48:145-53 

 
17. Lew HL, Otis JD, Tun C, Kerns RD, Clark ME, Cifu DX. Prevalence of chronic pain, 
posttraumatic stress disorder and persistent postconcussive symptoms in OIF/OEF veterans: 
polytrauma clinical triad. J Rehabil Res Dev. 2009;46(6):697-702. 
18. Department of Veterans' Affairs. Veterans' Health Administration. Pain Management, VHA 
Directive 2009-053. October 28, 2009; www.va.gov/painmanagement/docs/ 
vha09paindirective.pdf. Accessed January 25, 2017. 
19. Nahin RL. Estimates of pain prevalence and severity in adults: United States, 2012. J Pain. 
2015;16(8):769-780. 
20. Knox J, Orchowski J, Scher DL, Owens BD, Burks R, Belmont P. The incidence of low back 
pain in active duty United States military service members. Spine. 2011;36:1492-1500. 
21. Armed Forces Health Surveillance Center. Absolute and relative morbidity burdens attributable 
to various illnesses and injuries, U.S. Armed Forces, 2014. MSMR. 2015;22(4):5-10. 
22. Department of Veterans' Affairs and Department of Defense. VA/DoD Clinical Practice 
Guideline for Diagnosis and Treatment of Low Back Pain. 2008; http://www.healthquality. 
va.gov/guidelines/Pain/ lbp/online/index.htm. Accessed January 12, 2017. 
23. Chen CX, Kroenke K, Stump TE, et al Estimating minimally important differences for the 
PROMIS pain interference scales: results from 3 randomized clinical trials. Pain. 2017 Dec 1. 
e-pub ahead of print. 
24. Amtmann D, Kim J, Chung H, Askew RL, Park R, Cook KF. Minimally important differences 
for Patient Reported Outcomes Measurement Information System pain interference for 
individuals with back pain. J Pain Res. 2016;9:251-5. 
25. Askew RL, Cook KF, Revicki DA, Cella D, Amtmann D. Evidence from diverse clinical 
populations supported clinical validity of PROMIS pain interference and pain behavior. J Clin 
Epidemiol. 2016;73:103-11. 
26. Mafi JN, McCarthy EP, Davis RB, Landon BE. Worsening trends in the management and 
treatment of low back pain. JAMA Intern Med. 2013;173:1573-1581. 
27. Fritz JM, Cleland JA, Brennan GP. Does adherence to clinical practice guidelines for patients 
with acute low back pain improve the quality of care delivered by physical therapists? Med 
Care. 2007;45(10):973-80. 
28. Graves JM, Fulton-Kehoe D, Jarvik JG, Franklin GM. Health care utilization and costs 
associated with adherence to clinical practice guidelines for early magnetic resonance imaging 
among workers with acute occupational low back pain. Health Serv Res. 2014; 49:645-665. 
29. Hanney WJ, Masaracchio M, Liu X, Kolber MJ. The influence of physical therapy guideline 
adherence on healthcare utilization and costs among patients with low back pain: a systematic 
review of the literature. PLoS One. 2016;11(6):e0156799. 
30. Fourney DR, Dettori JR, Hall H, et al. A systematic review of clinical pathways for lower back 
pain and introduction of the Saskatchewan Spine Pathway. Spine. 2011;36(21 Suppl):S164-71. 
31. Paskowski I, Schneider M, Stevans J, Ventura JM, Justice BD. A hospital-based standardized 
spine care pathway: report of a multidisciplinary, evidence-based process. J Manipul Physiol 
Ther. 2011;34(2):98-106. 
32. Dobscha SK, Corson K, Perrin NA, et al. Collaborative care for chronic pain in primary care: a 
cluster randomized trial. JAMA. 2009;301(12):1242-1252. 

 
33. U.S. Army Medical Command. ARMY PCMH Implementation Manual Leaders Guide to 
Army Patient Centered Medical Home Transformation. 2nd ed. 2014. http://www.usafp.org/wp-
content/uploads/ 2013/12/Army_PCMH-Implementation-Manual-Final-30-Jan-14.pdf. 
Accessed January 20, 2017 
34. Katon W, Von Korff M, Lin E, et al. Stepped collaborative care for primary care patients with 
persistent symptoms of depression: a randomized trial. Arch Gen Psychiat. 1999;56: 1109-15. 
35. Bernstein IA, Malik Q, Carville S, Ward S. Low back pain and sciatica: summary of NICE 
guidance. BMJ. 2017;356:i6748. 
36. Chou R, Huffman LH. Nonpharmacologic therapies for acute and chronic low back pain: a 
review of the evidence for an American Pain Society/American College of Physicians clinical 
practice guideline. Ann Intern Med. 2007;147:492-504. 
37. Chou R, Huffman LH. Medications for acute and chronic low back pain: a review of the 
evidence for an American Pain Society/American College of Physicians Clinical Practice 
Guideline. Ann Intern Med. 2007;147:505-14. 
38. Chou R, Qaseem A, Owens DK, Shekelle P. Diagnostic imaging for low back pain: advice for 
high-value health care from the American College of Physicians. Ann Intern Med. 
2011;154:181-9. 
39. Nahum-Shani I, Qian M, Almirall D, et al. Q-learning: a data analysis method for constructing 
adaptive interventions. Psychological Methods. 2012;17:478-94. 
40. Moodie E, Richardson T. Estimating optimal dynamic regimes: correcting bias under the null. 
Scand J Stat. 2010;37:126-46. 
41. Chakraborty B, Laber EB, Zhao Y. Inference for optimal dynamic treatment regimes using an 
adaptive m-out-of-n bootstrap scheme. Biometrics. 2013;69:714-23. 
42. Fritz JM, Cleland JA, Speckman M, Brennan GP, Hunter SJ. Physical therapy for acute low 
back pain: associations with subsequent health care costs. Spine. 2008;33:1800-1805. 
43. Rhon DI. A physical therapist experience, observation, and practice with an infantry brigade 
combat team in support of Operation Iraqi Freedom. Mil Med. 2010;175(6):442-447. 
44. Rhon DI, Gill N, Teyhen D, Scherer M, Goffar S. Clinician perception of the impact of 
deployed physical therapists as physician extenders in a combat environment. Mil Med. 
2010;175(5):305-312. 
45. Alsaadi SM, McAuley JH, Hush JM, et al. Poor sleep quality is strongly associated with 
subsequent pain intensity in patients with acute low back pain. Arthritis Rheumatol. 
2014;66:1388-94. 
46. Brooks DE, Agochukwu UF, Arrington ED, Mok JM. Psychological distress in the active duty 
military spine patient. Mil Med. 2013;178(10):1059-1064. 
47. Hiebert R, Campello MA, Weiser S, et al. Predictors of short-term work-related disability 
among active duty US Navy personnel: a cohort study in patients with acute and subacute low 
back pain. Spine J. 2012;12(9):806-16. 
48. Tick H. Nutrition and pain. Phys Med Rehabil Clin N Am. 2015;26(2):309-20. 
49. Vargas-Prada S, Coggon D. Psychological and psychosocial determinants of musculoskeletal 
pain and associated disability. Best Pract Res Clin Rheumatol. 2015;29(3):374-90. 

 
50. National Institutes of Health. National Pain Strategy: A Comprehensive Population Health-
Level Strategy for Pain. 2016. https://iprcc.nih.gov/docs/HHSNational_Pain_Strategy.pdf. 
Accessed February 3, 2017. 
51. Bath B, Trask C, McCrosky J, Lawson J. A biopsychosocial profile of adult Canadians with 
and without chronic back disorders: a population-based analysis of the 2009-2010 Canadian 
Community Health Surveys. BioMed Res Int. 2014;2014:919621. 
52. Heuch I, Heuch I, Hagen K, Zwart JA. Is there a U-shaped relationship between physical 
activity in leisure time and risk of chronic low back pain? A follow-up in the HUNT Study. 
BMC Pub Health. 2016;16:306. 
53. Geneen LJ, Moore RA, Clarke C, et al. Physical activity and exercise for chronic pain in 
adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017;1:Cd011279. 
54. Naugle KM, Riley JL. Self-reported physical activity predicts Pain inhibitory and facilitatory 
function. Med Sci Sports Exerc. 2014;46:622-629. 
55. Orr LC, George SZ, Simon CB. Association between physical activity and pain processing in 
adults with chronic low back pain compared to pain-free controls. J Back Musculoskel 
Rehabil. 2017;30(3):575-81. 
56. Durmus D, Unal M, Kuru O. How effective is a modified exercise program on its own or with 
back school in chronic low back pain? A randomized-controlled clinical trial. J Back 
Musculoskel Rehabil 2014; 27(4):553-61. 
57. Krein SL, Kadri R, Hughes M, et al. Pedometer-based internet-mediated intervention for adults 
with chronic low back pain: randomized controlled trial. J Med Internet Res. 2013;15(8):e181. 
58. Fritz JM, Kim J, Thackeray A, Dorius J. Use of physical therapy for low back pain by 
Medicaid enrollees. Phys Ther. 2015. 95(12):1668-79. 
59. Shiri R, Karppinen J, Leino-Arjas P, Solovieva S, Viikari-Juntura E. The association between 
obesity and low back pain: a meta-analysis. Am J Epidemiol. 2010;171(2):135-154. 
60. Ray L, Lipton RB, Zimmerman ME, Katz MJ, Derby CA. Mechanisms of association 
between obesity and chronic pain in the elderly. Pain. 2011;152:53-59. 
61. Liang L, Lutz BM, Bekker A, Tao YX. Epigenetic regulation of chronic pain. Epigenomics. 
2015;7(2):235-45. 
62. De Gregori M, Muscoli C, Schatman ME, et al. Combining pain therapy with lifestyle: the 
role of personalized nutrition and nutritional supplements according to the SIMPAR Feed 
Your Destiny approach. J Pain Res. 2016;9:1179-89. 
63. Tang NK, Wright KJ, Salkovskis PM. Prevalence and correlates of clinical insomnia co-
occurring with chronic back pain. J Sleep Res. 2007;16(1):85-95. 
64. Schalet BD, Pilkonis PA, Yu L, et al. Clinical validity of PROMIS depression, anxiety and 
anger across diverse clinical samples. J Clin Epidemiol. 2016;73:119-27. 
65. Buysse DJ, Yu L, Moul DE,et al. Development and validation of patient-reported outcome 
measures for sleep disturbance and sleep-related impairment. Sleep. 2010;33:781–92. 
66. Caravalho J. Improving soldier health and performance by moving Army medicine toward a 
system for health. J Strength Cond Res. 2015;29(11):S4-S9. 
67. Teyhen DS, Aldag M, Centola D, et al. Incentives to create and sustain healthy behaviors: 
technology solutions and research needs. Mil Med. 2014;179(12):1419-1431. 

 
68.  Amirfez R, Pentlow A, Foote J, Leslie I. Assessing the clinical significance of change scores 
following carpal tunnel surgery. Int Orthop. 2009; 33: 181-5. 
69. Krejci LP, Carter K, Gaudet T. Whole Health. The vision and implementation of personalized, 
proactive, patient-driven health care for veterans. Med Care. 2014;52(suppl):S5-S8. 
70. Grotle M, Brox JI, Glomsrod B, Lonn JH, Vollestad NK. Prognostic factors in first-time care 
seekers due to acute low back pain. Eur J Pain. 2007;11(3):290-298. 
71. Grotle M, Foster NE, Dunn KM, Croft P. Are prognostic indicators for poor outcome different 
for acute and chronic low back pain consulters in primary care? Pain. 2010;151:790-797. 
72. Main CJ, Foster N, Buchbinder R. How important are back pain beliefs and expectations for 
satisfactory recovery from back pain? Best Pract Res Clin Rheumatol. 2010;24:205-217. 
73. Andronis L, Kinghorn P, Qiao S, Whitehurst DG, Durrell S, McLeod H. Cost-effectiveness of 
non-invasive and non-pharmacological interventions for low back pain: a systematic literature 
review. Appl Health Econ Health Policy. 2016. Aug 23, e-pub ahead of print. 
74. Brox JI, Storheim K, Grotle M, et al. Systematic review of back schools, brief education, and 
fear-avoidance training for chronic low back pain. Spine J. 2008;8(6):948-58. 
75. Rhon D, Fritz J. COMParative Early Treatment Effectiveness between physical therapy and 
usual care for low back pain (COMPETE): study protocol for a randomized controlled trial. 
Trials. 2015;16:423. 
76. Foster NE, Thomas E, Bishop A, Dunn KM, Main CJ. Distinctiveness of psychological 
obstacles to recovery in low back pain patients in primary care. Pain. 2009;148;3:398-406 
77. Stratton KJ, Hawn SE, Amstadter AB, Cifu DX, Walker WC. Correlates of pain symptoms 
among Iraq and Afghanistan military personnel following combat-related blast exposure. J 
Rehabil Res Dev. 2014;51(8):1189-1202. 
78. Stratton KJ, Clark SL, Hawn SE, Amstadter AB, Cifu DX, Walker WC. Longitudinal 
interactions of pain symptoms and posttraumatic stress disorder In U.S. military service 
members following blast exposure. J Pain. 2014;15(10):1023-1032. 
79. Dabbs C, Watkins EY, Fink DS, et al Opiate-related dependence/abuse and PTSD exposure 
among the active-component U.S. military, 2001 to 2008. Mil Med. 2014;179(8):885-90. 
80. Azulay CM, Smart T, Mott KD, Cicerone N. A pilot study examining the effect of 
mindfulness-based stress reduction on symptoms of chronic mild traumatic brain injury/ 
postconcussive syndrome. J Head Trauma Rehabil. 2013;28(4):323-331. 
81. Garland EL, Roberts-Lewis A, Tronnier CD, et al. Mindfulness-Oriented Recovery 
Enhancement versus CBT for co-occurring substance dependence, traumatic stress and 
psychiatric disorders: Proximal outcomes from a pragmatic randomized trial. Behav Res 
Ther. 2016;77:7-16. 
82. Hernandez TD, Brenner LA, Walter KH, et al. Complementary and alternative medicine 
(CAM) following traumatic brain injury (TBI): Opportunities and challenges. Brain Res. 
2016;1640(Pt A):139-151. 
83. King AP, Block SR, Sripada RK, et al. A Pilot Study of Mindfulness-Based Exposure 
Therapy in OEF/OIF Combat Veterans with PTSD: Altered Medial Frontal Cortex and 
Amygdala Responses in Social-Emotional Processing. Frontiers Psychiat. 2016;7:154. 

 
84. Tang YY, Holzel BK, Posner MI. The neuroscience of mindfulness meditation. Nat Rev 
Neurosci. 2015;16(4):213-225. 
85. Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption 
in chronic pain. Nat Rev Neurosci. 2013;14(7):502-511. 
86. Hardin JW. Generalized Estimating Equations. Hoboken, NJ: John Wiley & Sons; 2005. 
87. Bender R, Lange S. Adjusting for multiple testing - how and why? J Clin Epidemiol. 
2001;54:343-9. 
88. Hilton L, Hempel S, Ewing BA, et al. Mindfulness meditation for chronic pain: systematic 
review and meta-analysis. Ann Behav Med. 2016. Sept 22, e-pub ahead of print. 
89. Garland EL, Manusov EG, Froeliger B,et al. Mindfulness-oriented recovery enhancement for 
chronic pain and prescription opioid misuse: results from an early-stage randomized controlled 
trial. J Consul Clin Psychol. 2014;82(3):448-459. 
90. Garland EL, Froeliger B, Howard MO. Mindfulness training targets neurocognitive mechanisms 
of addiction at the attention-appraisal-emotion interface. Frontiers Psychiat. 2014;4:173. 
91. Garland EL, Howard MO. Mindfulness-oriented recovery enhancement reduces pain 
attentional bias in chronic pain patients. Psychother Psychosom. 2013;82(5):311-318. 
92. Childs JD, Piva SR, Fritz JM. Responsiveness of the numeric pain rating scale in patients with 
low back pain. Spine. 2005;30:1331-5. 
93. Murphy SA. An experimental design for the development of adaptive treatment strategies. Stat 
Med. 2005;24:1455-81. 
94. Little RJ, Rubin DB. Statistical analysis with missing data. Hoboken, NJ: John Wiley & Sons; 
2014. 
95. Schafer JL. Multiple imputation: a primer. Stat Meth Med Res. 1999;8:3-15. 
96. Von Korff M, Saunders K, Ray GT, et al. Defacto long-term opioid therapy for non-cancer 
pain. Clin J Pain. 2008;24:521-7. 
97. Fitzmaurice GM, Laird NM, Ware JH. Applied Longitudinal Analyses. Hoboken, NJ: John 
Wiley & Sons; 2012. 
98. Rhon DI, Teyhen DS, Shaffer SW, et al. Developing predictive models for return to work using 
the Military Power, Performance and Prevention (MP3) musculoskeletal injury risk algorithm: 
a study protocol for an injury risk assessment programme. Inj Prev. 2018. 24:81-8. 
99. Teyhen DS, Rhon DI, Butler RJ, et al. Association of physical inactivity, weight, smoking, and 
Prior Injury on Physical Performance in a Military Setting. J Athl Training. 2016;51:866-75. 
100. Teyhen DS, Shaffer SW, Butler RJ, et al. Application of athletic movement tests that predict 
injury risk in a military population: development of normative data. Mil Med. 2016; 
181:1324-34. 
101. Teyhen DS, Shaffer SW, Butler RJ, et al. What Risk Factors Are Associated With 
Musculoskeletal Injury in US Army Rangers? A Prospective Prognostic Study. Clin Orthop 
Relat Res. 2015;473(9):2948-2958. 
102. Fritz JM, Koppenhaver SL, Kawchuk GN, Teyhen DS, Hebert JJ, Childs JD. Preliminary 
investigation of the mechanisms underlying the effects of manipulation: exploration of a 

 
multivariate model including spinal stiffness, multifidus recruitment, and clinical findings. 
Spine. 2011;36:1772-81. 
103. Hebert JJ, Fritz JM, Thackeray A, Koppenhaver SL, Teyhen D. Early multimodal 
rehabilitation following lumbar disc surgery: a randomised clinical trial comparing the 
effects of two exercise programmes on clinical outcome and lumbar multifidus muscle 
function. Brit J Sports Med. 2015;49(2):100-106. 
104. Koppenhaver SL, Fritz JM, Hebert JJ, et al. Association between history and physical 
examination factors and change in lumbar multifidus muscle thickness after spinal 
manipulation in patients with low back pain. J Electromyo Kines 2012;22(5):724-731. 
105. Koppenhaver SL, Hebert JJ, Kawchuk GN, et al. Criterion validity of manual assessment of 
spinal stiffness. Man Ther. 2014;19(6):589-594. 
106. Deyle GD, Gill NW, Allison SC, Hando BR, Rochino DA. Knee OA: which patients are 
unlikely to benefit from manual PT and exercise? J Fam Prac. 2012;61(1):E1-8. 
107. Hando BR, Gill NW, Walker MJ, Garber M. Short- and long-term clinical outcomes following 
a standardized protocol of orthopedic manual physical therapy and exercise in individuals with 
osteoarthritis of the hip: a case series. J Man Manipul Ther. 2012;20:192-200. 
108. Goff BJ, Naber JW, McCallin JP, et al. Immediate return to ambulation and improved 
functional capacity for rehabilitation in complex regional pain syndrome following early 
implantation of a spinal cord stimulation system. Case Rep Anesthesiol. 2014;2014:784021. 
109. Goff BJ, Walker GA, Gloystein DM. Combat soldier loads: implications for cumulative 
overuse injuries and chronic pain. PM R. 2011;3(2):183-5. 
110. Fritz JM, Delitto A, Erhard RE. Comparison of classification-based physical therapy with 
therapy based on clinical practice guidelines for patients with acute low back pain: a 
randomized clinical trial. Spine. 2003;28(13):1363-71. 
111. Fritz JM, Magel JS, McFadden M, et al. Early physical therapy vs. usual care in patients with 
recent-onset low back pain: a randomized clinical trial. JAMA. 2015;314(14):1459-67. 
112. Fritz JM, Kim M, Magel JS, Asche CV. Cost-effectiveness of primary care management with 
or without early physical therapy for patients with acute low back pain: economic evaluation 
of a randomized clinical trial. Spine. 2017;42(5):285-90 
113. Fritz JM, Brennan GP, Hunter SJ, Magel JS. Initial management decisions after a new 
consultation for low back pain: implications of the usage of physical therapy for subsequent 
health care costs and utilization. Arch Phys Med Rehabil. 2013;94(5):808-16. 
114. Fritz JM, Kim J, Dorius J. Importance of the type of provider seen to begin health care for a 
new episode low back pain: associations with future utilization and costs. J Eval Clin Pract. 
2016;22:247-52. 
115. Greene T, Joffe M, Hu B, Li L, Boucher K. The balanced survivor average causal effect. Int 
J Biostat. 2013;9:291-306. 
116. Joffe MM, Greene T. Related causal frameworks for surrogate outcomes. Biometrics. 
2009;65:530-8. 
117. Davis LL, Kroenke K, Monahan P, Kean J, Stump TE. The SPADE Symptom Cluster in 
Primary Care Patients With Chronic Pain. Clin J Pain. 2016;32(5):388-393. 

 
118. Kean J, Monahan PO, Kroenke K, et al. Comparative Responsiveness of the PROMIS Pain 
Interference Short Forms, Brief Pain Inventory, PEG, and SF-36 Bodily Pain Subscale. Med 
Care. 2016;54(4):414-21. 
119. Kroenke K, Wu J, Yu Z, et al. Patient Health Questionnaire Anxiety and Depression Scale: 
Initial Validation in Three Clinical Trials. Psychosom Med. 2016;78(6):716-727. 
120. Witkin LR, Zylberger D, Mehta N, et al. Patient-Reported Outcomes and Opioid Use in 
Outpatients With Chronic Pain. J Pain. 2017. Jan 12, e-pub ahead of print 
121. Vanneman ME, Harris AH, Chen C, et al. Army Active Duty Members' Linkage to Veterans 
Health Administration Services After Deployments to Iraq or Afghanistan and Following 
Separation. Mil Med. 2015;180(10):1052-58. 
122. Office of the Assistant Secretary of Defense for Health Affairs, TRICARE Management 
Activity. Guide for DoD Researchers on Using MHS Data.  October 10, 2012. 
http://www.health.mil/Reference-Center/ Publications/2012/10/10/Guide-for-DoD-
Researchers-on-Using-MHS-Data. Accessed January 10, 2017.  
123. Cella D, Riley W, Stone A, et al. The Patient-Reported Outcomes Measurement Information 
System (PROMIS) developed and tested its first wave of adult self-reported health outcome 
item banks: 2005-2008. J Clin Epidem. 2010;63:1179-94. 
124. Cook KF, O'Malley KJ, Roddey TS. Dynamic assessment of health outcomes: time to let the 
CAT out of the bag? Health Serv Res. 2005;40(5 Pt 2):1694-1711. 
125. Zozus MN, Hammond WE, Green BB, et al. Assessing data quality for healthcare systems 
data used in clinical research. NIH Health Care Systems Collaboratory, Version 1.0, 2013. 
126. Simmonds MJ, Derghazarian T, Vlaeyen JW. Physiotherapists' knowledge, attitudes, and 
intolerance of uncertainty influence decision making in low back pain. Clin J Pain. 
2012;28:467-74. 
127. Beneciuk JM, George SZ. Pragmatic implementation of a stratified primary care model for 
low back pain management in outpatient physical therapy settings: two-phase, sequental 
preliminary study. Phys Ther. 2015;95(8):1120-1134. 
128. Overmeer T, Boersma K, Denison E, Linton SJ. Does teaching physical therapists to deliver 
a biopsychosocial treatment program result in better patient outcomes? A randomized 
controlled trial. Phys Ther. 2011;91(5):804-819. 
129. Defense & Veterans' Center for Integrative Pain Management. Joint Pain Education Project 
(JPEP). http://www.dvcipm.org/clinical-resources/joint-pain-education-project-jpep-1. 
Accessed February 2, 2017. 
130. National Guideline Center (UK). Low Back Pain and Sciatica in Over 16s: Assessment and 
Management. 2016; https://www.ncbi.nlm.nih.gov/books/NBK401577/. Accessed February 
10, 2017. 
131. Bekkering GE, Hendriks HJM, Koes BW, Oostendorp RA, Thomassen JMC, van Tulder 
MW. Dutch physiotherapy guidelines for low back pain. Physiotherapy. 2003;89:82-96. 
132. Koes BW, van Tulder MW, Lin CC, Macedo LG, McAuley J, Maher C. An updated 
overview of clinical guidelines for the management of non-specific low back pain in primary 
care. Eur Spine J. 2010;19(12):2075-94. 

 
133. Main CJ, George SZ. Psychologically informed practice for management of low back pain: 
future directions in practice and research. Phys Ther. 2011;91(5):820-824. 
134. Foster NE, Delitto A. Embedding psychosocial perspectives within clinical management of 
low back pain: integration of psychosocially informed management principles into physical 
therapist practice--challenges and opportunities. Phys Ther. 2011;91:790-803. 
135. Sanders T, Foster NE, Bishop A, Ong BN. Biopsychosocial care and the physiotherapy 
encounter: physiotherapists' accounts of back pain consultations. BMC Musculoskelet Disord. 
2013;14:65. 
136. Hill JC, Dunn KM, Lewis M, et al. A primary care back pain screening tool: identifying 
patient subgroups for initial treatment. Arthritis Rheum. 2008;59:632-41. 
137. Main CJ, Sowden G, Hill JC, Watson PJ, Hay EM. Integrating physical and psychological 
approaches to treatment in low back pain: the development and content of the STarT Back 
trial's 'high-risk' intervention. Physiotherapy. 2012;98:110-6. 
138. Caigne B, Vinck E, Beernaert A, Cambier D. How common are side effects of spinal 
manipulation and can these side effects be predicted? Manual Ther. 2004;9:151-156. 
139. Rozental A, Kottorp A, Boettcher J, Andersson G, Carlbring P. Negative effects of psycho-
logical treatments: an exploratory factor analysis of the negative effects questionnaire for 
monitoring and reporting adverse and unwanted events. PLoS ONE, 11(6), e0157503. 
140. Garland EL. Mindfulness-Oriented Recovery Enhancement for Addiction, Stress, and Pain. 
Washington, DC: NASW Press; 2013. 
141. Garland EL, Farb NA, Goldin P, Fredrickson BL. Mindfulness broadens awareness and 
builds eudaimonic meaning: a process model of mindful positive emotion regulation. Psychol 
Inquiry. 2015;26(4):293-314. 
142. Garland EL, Froeliger B, Howard MO. Neurophysiological evidence for remediation of 
reward processing deficits in chronic pain and opioid misuse following treatment with 
Mindfulness-Oriented Recovery Enhancement: exploratory ERP findings from a pilot RCT. J 
Behav Med. 2014. 
143. Pujol LA, Sussman L, Clapp J, et al. Functional restoration for chronic pain patients in the 
military: early results of the San Antonio Military Medical Center functional restoration 
program. US Army Med Depart J. 2015:1-7. 
144. Jonas WB, Welton RC, Delgado RE, Gordon S, Zhang W. CAM in the United States 
military. Too little of a good thing? Med Care. 2014;52:S9-S12. 
145. Deyo RA, Dworkin SF, Amtmann D, et al. Focus article report of the NIH task force on 
research standards for chronic low back pain. Clin J Pain. 2014;30:701-12. 
146. Tubach F, Ravaud P, Martin-Mola E, et al. Minimum clinically important improvement and 
patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing 
spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: Results 
from a prospective multinational study. Arthritis Care Res. 2012;64:1699-1707. 
147. Buysse DJ, Reynolds CF, 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep 
Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 
1989;28(2):193-213. 

 
148. Plumb TR, Peachey JT, Zelman DC. Sleep disturbance is common among servicemembers 
and veterans of Operations Enduring Freedom and Iraqi Freedom. Psychol Serv. 
2014;11(2):209-19. 
149. Prins A, Ouimette P, Kimberling R, et al. The primary care PTSD screen (PC-PTSD): 
development and operating characteristics. Prim Care Psychiatry. 2004;9:9-14. 
150. Hurst H, Bolton J. Assessing the clinical significance of change scores recorded on subjective 
outcome measures. J Manipulative Physiol Ther. 2004; 27:26- 35 
151. Bliese PD, Wright KM, Adler AB, Cabrera O, Castro CA, Hoge CW. Validating the primary 
care posttraumatic stress disorder screen and the posttraumatic stress disorder checklist with 
soldiers returning from combat. J Cons Clin Psychol. 2008;76(2):272-281. 
152. Wyrich KW, Nienaber N, Teirney W, Wolinksy FD. Linking clinical relevance and statistical 
significance in evaluating intra-individual changes in health-related quality of life. Med Care. 
1999: 37;469-78. 
153. Aralis HJ, Macera CA, Rauh MJ, Macgregor AJ. Traumatic brain injury and PTSD screening 
efforts evaluated using latent class analysis. Rehabil Psychol. 2014;59(1):68-78. 
154. Cook K, Kallen M, Cella D, et al. The Patient Reported Outcomes Measurement Information 
System (PROMIS®) Perspective on: Universally-Relevant vs. Disease-Attributed Scales. 
2014; http://www.healthmeasures.net/images/PROMIS/Universally-Relevant_vs_Disease-
Attributed_2014-2-12_final508.pdf. Accessed January 14, 2017 
155. EuroQol Group. EuroQol–A new facility for the measurement of health-related quality of 
life. Health Policy. 1990;16:199-208. 
156. Dolan P, Gudex C, Kind P, et al. The time trade-off method: results from a general 
population survey. Health Econ. 1996;5:141-154. 
157. Polomano RC, Galloway KT, Kent ML, et al. Psychometric testing of the Defense and 
Veterans Pain Rating Scale (DVPRS): a new pain scale for military population. Pain Med. 
2016;17:1505-19. 
158. Buckenmaier CC, Galloway K, Polomano R, et al. Preliminary validation ofthe Defense and 
Veterans Pain Rating Scale (DVPRS) in a military population. Pain Med. 2013;14:110-23. 
159. Defense & Veterans' Center for Integrative Pain Management.. Defense & Veterans Pain 
Rating Scale (DVPRS).  http://www.dvcipm.org/clinical-resources/pain-rating-scale. 
Accessed February 10, 2017. 
160. Tubach F, Dougados M, Falissard B, Baron G, Logeart I, Ravaud P. Feeling good rather than 
feeling better matters more to patients. Arthritis Rheum. 2006;55:526-530. 
161. Zgierska A, Wallace MI, Burzinski CA, Cox J, Backonja M. Pharmacological and 
toxicological profile of opioid-treated, chronic low back pain patients entering a mindfulness 
intervention randomized controlled trial. J Opioid Manag. 2014;10(5):323-35. 
162. Krebs EE, Lorenz KA, Bair MJ, et al. Development and initial validation of the PEG, a three-
item scale assessing pain intensity and interference. J Gen Intern Med. 2009;24:733-8.  
163. Hogue A, Dauber S, Lichvar E, Bobek M, Henderson CE. Validity of therapist self-report 
ratings of fidelity to evidence-based practices for adolescent behavior problems: 
correspondence between therapists and observers. Adm Policy Ment Health. 2015;42:229-43. 

 
164. Nahum-Shani I, Qian M, Almirall D, et al. Experimental design and primary data analysis 
methods for comparing adaptive interventions. Psychological Methods. 2012;17:457-77. 
165. Almirall D, Nahum-Shani I, Sherwood NE, Murphy SA. Introduction to SMART designs for 
the development of adaptive interventions: with application to weight loss research. Trans 
Behav Med. 2014;4:260-74. 
166. Chakraborty B, Murphy SA. Dynamic treatment regimes. Ann Rev Stat Applic. 2014;1:447-64. 
167. Lu X, Nahum-Shani I, Kasari C, et al. Comparing dynamic treatment regimes using repeated-
measures outcomes: modeling considerations in SMART studies. Stat Med. 2016;35:1595-1615. 
168. Glick HA, Dashi JA, Sonnad SS, Palsky D. Economic Evaluation in Clinical Trials. 2nd ed. 
New York, NY: Oxford University Press; 2014. 
169. Cohen J. A power primer. Psychol Bull. 1992;1:155-159. 
170.  Hruby A, Bulathsinhala L, MicKinnon CJ, et al. Body mass index at accession and incident 
cardio-metabolic risk factors in US Army soldiers, 2001–2011. PLOS One. 2017; 
12(1):e0170144 
171.  Anderson MK, Grier T, Canham-Chervak M, et al. Effect of mandatory unit and individual 
physical training on fitness in military men and women. Am J Health Prom. 2016; September 
16, e-pub ahead of print. 
172. Mysliwiec V, McGraw L, Pierce R, et al Sleep disorders and associated medical comorbidities in 
active duty military personnel. Sleep. 2013;36(2):167-174. 
173. Department of Veterans Affairs and Department of Defense. VA/DoD Clinical Practice 
Guideline for Assessment and Management of Patients at Risk for Suicide. Version 1.0, June 
2013. http://www.healthquality.va.gov/guidelines/MH/srb/VADODCP_SuicideRisk_Full.pdf . 
Accessed February 18, 2017. 
174. Dube P, Kroenke K, Bair MJ, Theobald D, Williams LS. The p4 screener: evaluation of a brief 
measure for assessing potential suicide risk in 2 randomized effectiveness trials of primary care 
and oncology patients. Prim Care Companion J Clin Psychiatry. 2010; 12(6). 
175.  Department of Veteran Affairs and Department of Defense. VA/DoD Clinical Practice 
Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. 
Version 3.0, June, 2017. https://www.healthquality.va.gov/guidelines/MH/ptsd/ 
VADoDPTSDCPGFinal.pdf. Accessed August 2, 2017. 
176.  Oetting AI, Levy JA, Weiss RD, Murphy SA. (2011). Statistical methodology for a SMART 
design in the development of adaptive treatment strategies, 179-205, in Shrout PE, Keyes KM, 
Ornstein K, (Eds.), Causality and psychopathology: Finding the determinants of disorders and 
their cures, American Psychiatric Publishing, Arlington, VA. 
177.  Rubin DB. Multiple imputation after 18+ years. J Am Stat Assoc. 1996 91(434):473-89. 
178.  Shortreed SM, Laber E, Stroup ST, Pineau J, Murphy SA. A multiple imputation strategy 
for sequential multiple assignment randomized trials. Stat Med, 2014;33(24):4202‐14. 
179.  Borm GF, Fransen J, Lemmens WA. A simple sample size formula for analysis of 
covariance in randomized clinical trials. J Clin Epidemiol. 2007;60(12):1234-8. 
180.  Lu X, Nahum-Shani I, Kasari C, et al. Repeated measures analysis of sequential, multiple 
assignment, randomized trials: modeling considerations. Stat Med. 2016;35:1595-1615. 

 
181. Resseguier N, Giorgi R, Paoletti X. Sensitivity analysis when data are missing not-at-
random. Epidemiology. 2011; 22(2):282. 
182. Van Buuren S, Boshuizen HC, Knook DL. Multiple imputation of missing blood pressure 
covariates in survival analysis. Stat Med 1999:18(6):681-94. 
183. Rhon DI, Lentz TA, George SZ. Unique contributions of body diagram scores and 
psychosocial factors to pain intensity and disability in patients With musculoskeletal pain. J 
Orthop Sports Phys Ther. 2017;47(2):88-96. 
 
 
 
 
 
 
 
 
 

 
 
 
APPENDIX II 
 
Intervention Manual of Operating Procedures 
 
 
 
 
 

 
 
 
 
 
 
 
 
APPENDIX III 
 
Informed Consent Document