Improving Veteran Access to Integrated Management of Back Pain: A Pragmatic, Cluster Randomized Trial
Phase: NA
Conditions: Low Back Pain, Veterans Family
Sponsor: Duke University

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Improving Veteran Access to Integrated Management of Back Pain 
(AIM-Back): An Embedded Pragmatic, Cluster Randomized Trial 
Principal Investigators: 
Steven Z. George, PT, PhD 
S. Nicole Hastings, MD, MHS
Supported by: 
The National Center for Complementary and Integrative Health (UH3AT009790) 
Study Procedures Provided by: 
Durham VA Health Care System 
Duke University  
Version Date: October 25, 2019 
NCT04411420

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Tool Revision History 
Version Number: 0.1  
Version Date: January 23rd 2019 
Summary of Revisions Made: Original source document was the grant proposal from March 
2017.  Protocol revisions were made in preparation for Duke University and Durham VA IRB 
submission, as well as for NCCIH protocol review.   
Revisions include: 1) updates to the care pathways from stakeholder engagement process; 2) 
modifications to sample size and analysis plan following Biostatistics Working Group review; 3) 
updated language on data sharing agreement; 4) detail on process for site selection; 5) 
description of process for capturing longitudinal data via the outcomes call center    
Version Number: 0.2 
Version Date: March 4th, 2019 
Summary of Revisions Made: This version of the protocol included updates from the initial 
NCCIH review including 1) updates on the selection process for participating sites; 2) additional 
details describing the care pathways (including updated care pathway figures); 3) better 
definitions for pathway adherence; 4) appendices for SPIRIT and TIDier documents; 5) 
answered queries from NIH review; and 6) appendix that includes the outline for pathway 
training materials (Milestone for completed materials is June 2019).   
Version Number: 0.3 
Version Date: May 3rd, 2019 
Summary of Revisions Made: This version of the protocol continues the responses and updates 
from NCCIH review including 1) Update on the sites that will participate in the clinical pathways; 
2) More detailed information on how improvement will be determined in the Coordinated Care
Pathway; 3) Protocol clarifications on inclusion criteria (for operational definition of LBP and
geographic distance); 4) Methodological clarification on how telephone subset will be selected;
5) Statistical analysis clarification regarding statistician role and clinic drop out; 6) Addition of
DSMP Template as Appendix to address Safety Monitoring portion of the protocol.
Version Number: 0.4  
Version Date: June 28, 2019  
Summary of Revisions Made: This version of the protocol contains responses to 1) Providing 
more details and plans for recruiting site recruitment and 2) updates on IRB approval for Duke 
University and Durham VA.  There is supporting documentation for these protocol updates sent 
along with this revised protocol.    
Version Number: 0.41  
Version Date: August 15, 2019  
Summary of Revisions Made: This version of the protocol includes: 1) Removed comments and 
accepted track changes for issues that appeared to be resolved; 2) IRB approval for Duke 
University and Durham VA approval that includes waiver of consent; 3) Fully executed data use 
agreement between Duke and Durham VA; 4) Updates to randomization schedule to account 

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for potential clinic dropout; 5) Site recruitment letter from VISN6 director indicating that site 
participation agreements can be pursued once protocol is finalized; 6) Updated data collection 
templates for creation of health factors in VA electronic health record; 7) Manuals for training 
sites in implementing the clinical pathways; 8) Added study logo to title page.     
Version Number: 0.50  
Version Date: October 25, 2019  
Summary of Revisions Made: This version of the protocol includes responses to the Protocol 
Review Committee comments from September 24 review call: 1) Clarified procedures and 
analysis plan for timing of 3-month primary endpoint ascertainment; 2) Provided additional 
information on the qualitative approach; 3) Provided additional information on implementation 
approach including theoretical framework and evaluation plans; 4) Updated contact of eligible 
subjects from 4 to up to 10 call attempts will be made; 5) Nomenclature updated for the CCP, 
removing all remnants of the CMP acronym.   
Additional updates made by the study team; 1) we now refer to AIM-Back as an “embedded 
pragmatic trial”, as this is a better descriptor of the study; 2) age specified as a patient level 
characteristic that will be considered for covariate constrained randomization;     

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TABLE OF CONTENTS 
 
Page 
Tool Revision History ................................................................................................................. 2 
TABLE OF CONTENTS ............................................................................................................. 4 
STUDY TEAM ROSTER........................................................................................................... 7 
PARTICIPATING CLINICS ...................................................................................................... 9 
PRÉCIS ..................................................................................................................................... 10 
1. STUDY OBJECTIVES ........................................................................................................... 13 
1.1 
Primary Objective ......................................................................................................... 13 
1.2 
Secondary Objectives.................................................................................................... 13 
2. BACKGROUND AND RATIONALE .................................................................................. 13 
2.1 
Background on Condition, Disease, or Other Primary Study Focus ............................ 13 
2.2 
Study Rationale ............................................................................................................. 14 
2.3 
Integrated Care Pathway ............................................................................................... 15 
2.4 
Coordinated Care Pathway ........................................................................................... 19 
3. STUDY DESIGN ..................................................................................................................... 21 
4. SELECTION AND ENROLLMENT OF CLINICAL SITES AND PARTICIPANTS ... 23 
4.1 
Participant Inclusion Criteria ........................................................................................ 23 
4.2 
Participant Exclusion Criteria ....................................................................................... 24 
4.3 
Study Enrollment Procedures for Outcome Collection ................................................ 24 
5. IMPLEMENTATION OF CARE PATHWAYS ................................................................. 26 
5.1 
Qualitative Data Collection........................................................................................... 26 
5.2 
Concomitant Interventions ............................................................................................ 26 
5.2 
Adherence Assessment ................................................................................................. 27 
6. STUDY PROCEDURES ........................................................................................................ 29 
6.1.1 Integrated Care Pathway ........................................................................................... 30 

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Central Delivery Physical Activity Phone Call Template ....................................................... 31 
Central Delivery 3-month follow-up Phone Call Data Collection Template ......................... 31 
6.1.2 Coordinated Care Pathway ....................................................................................... 31 
6.2 
VA Corporate Data Warehouse Collection ................................................................... 32 
6.3 
Blinding..................................................................................................................... 32 
Blinding................................................................................................................................. 32 
7. SAFETY ASSESSMENTS ..................................................................................................... 34 
7.1 
Adverse Events and Serious Adverse Events ............................................................... 34 
7.2 
Safety Monitoring ......................................................................................................... 35 
8. CLINIC DISCONTINUATION ............................................................................................ 35 
9. STATISTICAL CONSIDERATIONS .................................................................................. 36 
9.1 
General Design Issues ................................................................................................... 36 
9.2 
Sample Size and Randomization .................................................................................. 37 
9.2.1 Treatment Assignment Procedures .............................................................................. 38 
9.3  
Definition of Populations .............................................................................................. 39 
9.4 
Interim Analyses and Stopping Rules ........................................................................... 39 
9.5 
Outcomes ...................................................................................................................... 39 
9.5.1 Primary Outcome ...................................................................................................... 39 
9.5.2 Secondary Outcomes ................................................................................................ 40 
9.6 
Data Analyses ............................................................................................................... 40 
10. MEASURES AND DATA COLLECTION ........................................................................ 44 
10.1 
Survey Data Collection Process .................................................................................... 45 
10.2 
Data Management ......................................................................................................... 46 
10.3 
Quality Assurance ......................................................................................................... 47 
10.3.2 
Quality Control Committee................................................................................... 47 
10.3.3 
Metrics .................................................................................................................. 47 
10.3.4 
Protocol Deviations ............................................................................................... 47 
10.3.5 
Monitoring ............................................................................................................ 48 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY ................................................... 48 
11.1 
Institutional Review Board (IRB) Review .................................................................... 49 
11.2 
Informed Consent Forms .............................................................................................. 49 
11.3 
Participant Confidentiality ............................................................................................ 49 
11.4 
Study Discontinuation ................................................................................................... 50 

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12. COMMITTEES..................................................................................................................... 50 
13. PUBLICATION OF RESEARCH FINDINGS .................................................................. 51 
14. REFERENCES ...................................................................................................................... 52 
15. SUPPLEMENTS/APPENDICES ........................................................................................ 57 
See Accompanying PDF with Appendices I - XI ...................................................................... 57 
I. 
VA Support Letters  
II. 
TIDier Summary for Integrated Care Pathway 
III. 
TIDier Summary for Coordinated Care Pathway 
IV. 
SPIRIT Table for AIM-Back Design  
V. 
Operation Manual for Pathway Training for Participating Sites  
VI. 
Data Collection Template - Integrated Care Pathway  
VII. 
Data Collection Template - Coordinated Care Pathway  
VIII. 
Randomization, Training, and Enrollment Flow Sheet  
IX. 
Detailed Data Flow for AIM-Back 
X. 
Script for Verbal Consent Approved by Durham VA IRB  
XI. 
Data Safety Monitoring Plan  
 

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STUDY TEAM ROSTER  
Name 
Address 
Telephone 
Fax 
E-mail 
Steven Z. George, 
PT, PhD (PI) 
DCRI, 200 
Morris St, 
Durham, 
NC 27701 
(919) 668-
0825 
(919)
684-
1846 
steven.george@duke.edu 
S. Nicole 
Hastings, MD, 
MHS (PI) 
Durham 
VAHCS, 
HSRD 
(152) 
508 Fulton 
St. 
Durham, 
NC 27705 
(919) 286-
6936 
(919) 
416-
5836 
susan.hastings@duke.edu 
Kelli Allen, PhD 
(Co-Investigator) 
Box 7280, 
UNC, 
Chapel 
Hill, NC 
27599 
(919) 966-
0558 
(919) 
966-
1739 
kdallen@email.unc.edu 
Chad Cook, PT, 
PhD, MBA (Co-
Investigator) 
DUMC 
104002, 
2200 W 
Main St. 
Ste B230, 
Durham, 
NC 27710 
(919) 684-
8905 
(919) 
684- 
1846 
chad.cook@duke.edu 
  
Corey Simon, 
DPT, PhD (Co-
Investigator) 
DUMC 
104002, 
2200 W 
Main St. 
Ste B230, 
Durham, 
NC 27710 
(919) 681-
1692 
(919) 
684- 
1846 
corey.simon@duke.edu 
Adam Goode, 
DPT, PhD (Co-
Investigator) 
DCRI, 200 
Morris St, 
Durham, 
NC 27701 
(919) 681-
6154 
(919)
684-
1846 
adam.goode@duke.edu 
Heather King, 
PhD (Co-
Investigator) 
Durham 
VAHCS, 
HSRD 
(152) 
508 Fulton 
St. 
Durham, 
(919) 286-
6936 
(919) 
416-
8025 
heather.king@duke.edu 

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NC 27705 
Catherine 
Stanwyck (Project 
Coordinator) 
Durham 
VAHCS, 
HSRD 
(152) 
508 Fulton 
St. 
Durham, 
NC 27705 
(919) 286-
6936 
(919) 
416-
5836 
catherine.stanwyck@duke.edu 
Leo Brothers 
(Project 
Coordinator) 
DCRI, 200 
Morris St, 
Durham, 
NC 27701 
(919) 668-
4601 
(919) 
668-
7124 
joseph.l.brothers@duke.edu 
Jennifer Naylor 
PhD  
508 Fulton 
St. 
Durham, 
NC 27705 
(919) 286-
0411 
x133631 
(919) 
416-
5912 
jennifer.naylor@duke.edu 
Cynthia Coffman, 
PhD (Statistical 
Investigator) 
Durham 
VAHCS, 
HSRD 
(152) 
508 Fulton 
St. 
Durham, 
NC 27705 
(919) 286-
6936 
(919) 
416-
8025 
cynthia.coffman@duke.edu 
Avi Alkon 
(Programmer) 
Durham 
VAHCS, 
HSRD 
(152) 
508 Fulton 
St. 
Durham, 
NC 27705 
(919) 286-
6936 
(919) 
416-
8025 
aviel.alkon@duke.edu 
Janet Grubber, MS Durham 
VAHCS, 
HSRD 
(152) 
508 Fulton 
St. 
Durham, 
NC 27705 
(919) 286-
6936 
(919) 
416-
8025 
janet.grubber@va.gov 
Ashley Choate, 
MPH 
Durham 
VAHCS, 
(919) 286-
6936 
(919) 
416-
5836 
ashley.choate@va.gov 

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HSRD 
(152) 
508 Fulton 
St. 
Durham, 
NC 27705 
 
PARTICIPATING CLINICS 
Sixteen VA medical center (VAMC) primary care clinics will be randomized to be trained to 
implement one of two care pathways for low back pain.  Both back pain care pathways being 
examined in this study represent best practices (not experimental interventions).  This position 
has been officially supported by the Department of Veteran Affairs in a memorandum stating 
“implementing the low back pain care pathways is a non-research operations/quality 
improvement activity” (Appendix I).  Employees at clinical sites that implement the back pain 
care pathways will participate in educational training for delivering the treatment as part of 
standard care and clinical program-related duties only.  All research activities involving human 
subjects (e.g., data collection and analysis) will be carried out by employees of the Durham VA 
Health Care System and Duke University in accordance with approved IRB protocols. 
 
The 16 primary care clinics included in AIM-Back training activities will be selected from the 
VAMCs supporting this embedded pragmatic trial, summarized in Table 1.  This group of 
Medical Centers provides a potential total of 39 clinics for randomization.  In further 
consideration of site selection criteria are factors of 1) patient volume (i.e. primary care clinics 
will be approached to participate in the AIM-Back study if they have 800-5,000 unique patients 
seen for low back pain in the preceding year) and 2) distinct provider pool (i.e. they do not share 
providers with another VA primary care clinic that would cause pathway contamination).  When 
these criteria are applied we are left with 23 clinics that have potential for randomization 
accounting for 41,190 patients with LBP visits in 2018 (Table 1, Column 5).   
 
These clinics will be approached for formal site participation agreements when the AIM-Back 
protocol is approved. VISN6 leadership’s position has been to hold on pursuing signed site 
participation agreements until then (Appendix I).   Durham (3 primary care clinics) has already 
verbally agreed to participation and we will continue discussion with other locations as part of 
“good faith” site recruitment efforts.  The good faith period will allow us to rapidly pursue formal 
site participation agreements once the protocol is finalized.   
  
 
Table 1. VA Medical Center Sites and Associated Primary 
Care Clinics   
  
 
VAMC  
Location 
Facility 
Complexity 
Level 
Number of 
Primary Care 
Clinics 
Number of 
Eligible 
Primary Care 
Clinics 
Total # pts with a 
LBP visit in 2018 
from Eligible 
Clinics  
Durham VAHCS  Durham, 
NC 
1a 
6 
3 
5,788 
Charles George 
VAMC  
Asheville, 
NC 
1c 
2 
2 
1,920 

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PRÉCIS  
Study Title  
Improving Veteran Access to Integrated Management of Back Pain (AIM-Back): A Pragmatic, 
Cluster Randomized Trial 
Objectives  
The overall objective of this large, embedded  pragmatic trial is to examine the effectiveness of 
two different care pathways for low back pain (LBP); 1) a sequenced, integrated care pathway 
and 2) a coordinated, care management pathway. The integrated care pathway involves three 
components including pain modulation with physical pain treatments (i.e. spinal manipulation, 
massage, or transcutaneous electrical nerve stimulation based on site availability), telephone 
delivered self-management counseling for increasing physical activity, and telephone delivered 
behavioral treatment for those identified to be at high risk for continued disability.  The care 
management pathway involves care coordination via a pain navigator who is knowledgeable of 
current guideline recommended treatments for LBP.  The pain navigator will engage in shared 
decision making with the Veteran to coordinate and sequence services based on guideline 
adherence by accounting for patient preference and emphasizing early use of non-
pharmacological treatments.   
 
The back pain care pathways in this study represent best practices thus, they will be 
implemented into routine clinical care at participating VA clinics. As part of a companion, IRB-
approved research evaluation, we will test the central hypothesis that the integrated care 
pathway will reduce pain interference with normal activities and improve physical function, as 
measured by PROMIS Short Form scores when compared to the care management pathway. 
Furthermore, we will determine participant characteristics associated with greater improvements 
in pain and function, and better adherence to each care pathway. Planned and appropriately 
powered subgroup analyses for treatment moderators of previous opioid exposure and chronic 
vs. acute LBP will also be completed. These additional analyses will inform the potential for 
matching subgroup characteristics to the delivery of a specific care pathway for better clinical 
outcomes for Veterans.  
Design and Outcomes   
This is a 4-year cluster randomized embedded pragmatic trial comparing the effectiveness of 
two care pathways for LBP.  The trial will test the central hypothesis that patients in an 
Fayetteville 
VAMC  
Fayetteville, 
NC 
2 
2 
0 
0 
Hampton 
VAMC  
Hampton, 
VA 
1c 
4 
1 
3,675 
Hunter Holmes 
McGuire VAMC  
Richmond, 
VA 
1a 
5 
3 
6,008 
Salem VAMC  
 
Salem, VA 
1c 
3 
1 
2,871 
W.G. (Bill) 
Hefner VAMC  
Salisbury, 
NC 
1c 
7 
5 
10,775 
James J. Peters 
VAMC 
Bronx, NY 
1c 
4 
1 
1,881 
Ralph H. 
Johnson VAMC  
Charleston, 
SC 
1c 
7 
7 
8,992 

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integrated care pathway will have reduced pain interference and improved physical function 
when compared to patients in a care management pathway.  We are testing these two care 
pathways because both have the potential to deliver guideline adherent, biopsychosocial-
oriented care but they have different implementation models.  For example, the integrated care 
pathway is structured to include physical activity,  risk stratification, and behavioral based care.  
However, these qualities also make this pathway more resource intensive. In contrast, the care 
management pathway is less disruptive to existing service delivery.  Therefore it is less 
resource intensive by taking advantage of existing VA resources,1 but we anticipate there will be 
more variability in the care received.  Therefore, determining the comparative effectiveness of 
these two care strategies is of high interest scientifically and also for improving non-
pharmacological pain management options for Veterans.         
  
VA primary care clinics that have agreed to have their clinical staff trained in offering these care 
pathways as standard clinical care will be randomly assigned to one of the two care pathways. 
A cluster randomized trial (CRT) was selected because it offers the most pragmatic and efficient 
design to address our aims due to the nature of the care pathways and interest in assessing 
both short and long-term outcomes. An important consideration in a CRT is the optimal unit of 
randomization. We will designate the unit of randomization as the VA clinic (rather than an 
entire VAMC ‘site’ or ‘station’) to 1) enhance feasibility of implementation, and 2) improve power 
(allows for higher number of clusters).  
 
Outcomes will be collected in the EHR at baseline and 3-month follow-up and for a subset of 
Veterans surveys will be administered at baseline with follow up points at 3, 6, 9, and 12 
months.  The primary outcomes (PROMIS pain interference and physical function) and 
secondary outcome (PROMIS sleep quality) will be captured in templated progress notes in the 
VA medical record for participants (n = 1,680) using PROMIS short form instruments (4 items 
per scale). A subset of these same participants (n=848) will be consented for the additional 
survey data collection.  These additional data will be used in the secondary and exploratory 
analyses; and the measures include more detailed patient reported outcomes on pain 
associated distress, physical function, and health care utilization as well as longer term follow-
up.    
Care Pathways and Duration  
The Integrated Care Pathway (ICP) includes both on-site physical therapy (PT) services 
(delivered by PT providers at each participating VA clinic) and centrally-delivered services via 
telehealth. The ICP will be initiated by a referral from a provider at a participating primary care 
clinic.  The first step of the ICP is contact by the central delivery provider to explain the ICP, 
determine preferences in delivery mode for centrally-delivered services (telephone vs video) 
and initiate onsite PT services.  Onsite PT services will include a physical examination, and pain 
modulation treatment as determined by the provider that could include manual therapy or 
electrotherapy and capture of baseline data on pain and function.  This first step will consist of a 
maximum of 2 on-site PT visits and it will take 2 weeks.  The second step of the ICP will last 6 
weeks, with patients receiving telehealth (i.e. telephone or video) calls for home physical activity 
instruction. The calls are will be conducted by centrally located Durham VA providers.  
The third step of the ICP is referral back to the onsite PT after completion of the 6 weeks of 
physical activity instruction for 1 visit consisting of additional pain modulation treatments (if 
needed) and completion of a simple 9-question risk stratification tool (Start Back Screening Tool 
(SBST)).  The SBST will be used to identify at higher risk for developing chronic or persistent 
back pain.  Patients scoring as ‘low risk’ on the SBST are discharged from PT services, and the 
ICP will end with notification to the primary care clinic.  Those patients scoring ‘medium or high 
risk’ on the SBST will receive 6 more weeks of ICP care consisting of weekly calls (telephone or 

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video) from providers at the Durham VA focused on psychological and behavioral activation 
components, consistent with what can be delivered by a physical therapist.  This third and final 
step of the ICP will consist of 6 treatment sessions over 6 weeks, but only for those that have 
been identified as medium or high risk on the SBST.  
The Coordinated Care Pathway (CCP) involves use of existing non-pharmacological services 
available at participating VAMCs.  The CCP will be initiated by a referral from a participating 
primary care clinic. The first step of the CCP is telephone or video (depending on availability 
and common practices at the site) contact with a pain navigator. The pain navigator will be an 
on-site provider trained to elicit patient preferences for non-pharmacological treatments and is 
knowledgeable in current recommended treatment guidelines for low back pain. The pain 
navigator will engage in a shared-decision making process with patients to determine the 
appropriate nonpharmacological, guideline supported VA service for their LBP.  The pain 
navigator will coordinate consultation of these services to increase the likelihood of receiving the 
interventions.  Consistent with the pragmatic nature of this trial, there will be no control of the 
duration or intensity of treatment received in the CCP.  However, we expect that receiving the 
first recommended service will take approximately 6 weeks.  If an additional service is needed, 
the above process will be repeated with the pain navigator to gain referral to another non-
pharmacological service.  This is expected to take another 6 weeks.  If additional services are 
requested after the second consult with the pain navigator the patient will be referred back to 
the primary care clinic for additional medical examination.  
 
These two care pathways were designed to improve access to evidence supported non-
pharmacological treatments for Veterans with low back pain.  The care pathways have this 
similar goal, but the process of delivery differs.  This is an embedded pragmatic trial so we 
expect some variation from what was described above in care delivery parameters.  This 
variability will be captured and accounted for in study related analyses described later in the 
protocol (e.g. adherence related analyses). 
   
Sample Size and Population  
Our target population is Veterans seeking care for acute and chronic LBP at VA primary care 
clinics. Eligible Veterans will have been deemed by their primary care provider as clinically 
appropriate for conservative management (i.e. no trauma, fracture, infection, or cancer) and 
given a pathway referral for LBP management. The total projected sample size is 1,680 
Veterans across 16 different clinical sites (n=105 per clinic) for the administrative sample with 
outcomes derived exclusively from the EHR. For the survey sample, which is approximately half 
of the projected administrative sample (n=848; 53 per clinic), recruitment will be balanced 
across the clinical sites.  The 16 clinics will be randomized in equal numbers to the ICP (N=8 
clinics) and CCP (N=8 clinics) arms. We plan on conducting a covariate constrained 
randomization2-4 with the following clinic level covariates assessed prior to randomization: 1) 
average pain scale scores of LBP patients at clinic, 2) average level of opioid exposure of LBP 
patients at clinic, 3) number of participating primary care providers at clinic, and 4) clinic location 
(main medical center/community clinic), and 5) average age of LBP patients at clinic. These 
characteristics were chosen to represent factors likely to be associated with baseline differences 
in patient population that may affect primary outcomes.  

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1. STUDY OBJECTIVES 
1.1 
Primary Objective 
Examine the effectiveness at 3 months of two care pathways for LBP: 1) an integrated care 
pathway (ICP) and 2) a coordinated care pathway (CCP).  We will test the central hypothesis 
that the ICP will reduce pain interference with normal activities and improve physical function, 
as measured by PROMIS Short Form scores when compared to the CCP.  
1.2 
Secondary Objectives 
We will compare the effect of two different LBP pathways on sleep quality, as measured by 
PROMIS Short Form scores. We will also determine participant characteristics associated with 
greater improvements in pain and function, and better adherence to each care pathway. 
Planned and appropriately powered subgroup analyses for treatment moderators of previous 
opioid exposure and chronic vs. acute LBP will be completed. We will identify multidimensional 
subgroups from baseline characteristics for treatment moderation of pain and function, as well 
as for care strategy adherence.  These additional analyses will inform the potential for 
identifying subgroup characteristics that indicated better clinical outcomes for Veterans in either 
care pathway.  
2. BACKGROUND AND RATIONALE 
2.1 
Background on Condition, Disease, or Other Primary Study Focus 
A 2011 report from the National Academy of Medicine (NAM, formerly the Institute of 
Medicine) described chronic pain as among the most prevalent, disabling, and costly medical 
problems in the United States.5  Direct cost estimates for overall healthcare expenditures for 
pain treatment in the US are remarkably high, and increase further when the societal cost of 
chronic pain is considered: including the value of lost work and lower wages, the total cost 
estimates range from $560 to $635 billion.5 Recognizing the growing extent of this burden, the 
IOM’s Interagency Pain Research Coordinating Committee (IPRCC) outlined priorities for pain 
research, treatment, education and policy in the National Pain Strategy (NPS).6  In particular, it 
identified two over-arching priorities to 1) identify methods for reducing the incidence of acute to 
chronic pain transition and 2) develop effective management strategies for high impact chronic 
pain conditions.7 Likewise, the 2010 - 2014 National Health Interview Survey illustrated the 
negative impact of chronic pain for Veterans.  When compared to non-Veterans, greater 
proportions of Veterans reported having; 1) pain in the previous 3 months (65.5% vs. 56.4% 
respectively); and 2) severe pain (9.1% vs. 6.3% respectively).8  These data and others 9,10 
show an urgent need for better pain management options in the VA health system.  
 
 
In addition to recognition of the burden of chronic pain, appreciation of non-pharmacological 
pain management as an effective, lower risk approach (as compared to common 
pharmacological or surgical approaches) has led multiple federal (e.g. CDC11) and non-federal 
(e.g. NAM5 and American College of Physicians (ACP)12) entities to strongly advocate for 
broader implementation of non-pharmacological pain management.  Indeed, coordinated efforts 
between the NIH, DoD, and VA have built the capacity for large-scale clinical research for non-
pharmacological approaches by supporting a coordinating center and demonstration projects for 
large scale embedded pragmatic trials . These are encouraging developments for the field. 
However, what constitutes best practice for non-pharmacological pain management is largely 
unknown.13  For example, there are still unanswered questions about structuring of non-
pharmacological care pathways to optimize clinical outcomes, diminish unwarranted diagnostic 

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testing (e.g. advanced imaging), and limit exposure to higher risk treatment pathways (e.g. 
opioids, injections, 
and/or surgery).13  
2.2 
Study 
Rationale 
Among conditions 
targeted for improved 
non-pharmacological 
pain management 
strategies, 
musculoskeletal pain, 
and LBP specifically, is 
a particular priority.5,6 
Of those affected, 
Veterans are more 
likely to have LBP or 
joint pain, and are more 
likely to report LBP or 
joint pain as severe when experienced.8 The widespread impact of LBP and the 
disproportionate impact of LBP on Veterans’ quality of life argue strongly for improvement in 
non-pharmacological pain management care pathways in the VA setting. Indeed, new care 
pathways that meet the needs of Veterans with LBP and are associated with favorable clinical 
outcomes represent a critical step  
forward in patient care.13 To advance understanding relevant to the above priorities, we will 
conduct a cluster randomized embedded pragmatic trial to develop infrastructure and 
investigate the comparative effectiveness of two different pain management strategies that have 
potential to improve access to non-pharmacological care for LBP.  The two pain management 
care pathways that will be evaluated in this trial are 1) an integrated care pathway (ICP) and 2) 
a coordinated care pathway (CCP). These two strategies share the common goal of leveraging 
existing VA infrastructure for non-pharmacological pain management of low back pain, but the 
structure of care delivery is notably different in terms of staff contact, provider approach, and 
care progression (Table 2).   
 
 
In this trial, we will determine whether these differences impact patient outcomes and/or health 
care utilization.  Evaluating two pain care pathways in a well-powered comparative effectiveness 
trial will help guide infrastructure development and contribute to novel understanding of 
implementation and performance in different clinical settings and situations. Other significant 
aspects of the proposed pain management strategies, including structuring care and following 
recommendations for biopsychosocial care and reducing variation in care, are further discussed 
below. 
 
In recognition of the high burden of pain on Veterans and associated costs to the health care 
system, VHA implemented a National Pain Management Strategy.1 This Strategy approaches 
pain care within a biopsychosocial framework and this has led to VA offering a broad array of 
services for pain care.  For example, VHA has specifically encouraged expansion of access to 
cognitive behavioral therapy for chronic pain management. However, a major barrier to 
organized and timely delivery of these services has been limited provider and Veteran 
awareness of them. Other barriers include lack of a standardized process for connecting 
patients to these services (e.g., who is responsible, which services are appropriate). In addition, 
recent legislation affecting financing of services outside of VA (e.g. CHOICE Act) has created a 
rapidly changing environment regarding how these services are organized, delivered, and paid. 
Table 2. Distinctions of the Two Care Pathways  
 
Integrated Care  
Coordinated Care  
Initiation 
Provider referral 
Provider referral 
Staff 
Contact 
Physical Therapist  
 
Pain Navigator  
Provider 
Approach 
Directed care -  
Pain modulation 
Home based activity,  
Risk stratification,  
Behavioral/psychologically 
informed treatment (if 
indicated)  
Coordinated care -    
Patient preference  
Guideline adherence  
Facilitated referrals to 
existing VA or non-VA 
pain management 
resources   
Care 
Progression 
Sequenced  
Stepped  

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This has increased confusion about how and when pain-related services should be offered to 
Veterans.  
 
VA clinics that have agreed to have their clinical staff trained in offering these care pathways as 
standard care will be randomly assigned to one of the two care pathways. A cluster randomized 
trial (CRT) was selected because it offers the most pragmatic and efficient design to address 
our aims. VA clinics implementing these back pain care pathways are not engaged in research 
because both pathways involve different ways of providing standard of care treatment.  
Employees at clinical sites that implement the back pain care pathways will participate in 
educational training for delivering the treatment as part of standard care and clinical program-
related duties only.  Employees delivering the clinical treatment will not be directly involved in 
any research related procedures (e.g. extraction of data from VA’s Corporate Data Warehouse 
or telephone surveys).  To assist each site in implementing the care pathways we will collect 
data and provide reports to be used for process improvement. These will include both 
quantitative (e.g. number of eligible patients, number of referrals, etc) and qualitative data 
collected from interviews with participating providers (e.g. exploring referral process and patient 
response to care pathways). 
2.3 
Integrated Care Pathway  
The Integrated Care Pathway (ICP) provides both on-site physical therapy (PT) services and 
centrally-delivered services via telephone or video from study providers at the Durham VA.  The 
ICP is initiated with a primary care referral to the pathway. Patients will start the ICP by 
receiving on-site PT services for 1-2 visits.  These visits will include examination, pain 
modulation treatment, and patient education.  After the on-site visit(s) patients will be referred to 
receive weekly calls for 6 weeks of home physical activity instruction.  These calls will be 
conducted by providers at the Durham VA.  After 6 weeks the patients will be instructed to 
return to the onsite PT services at participating clinics. Patients then complete a simple 9-
question risk stratification tool (SBST) patients scoring ‘medium or high risk’ on the SBST will 
receive additional centrally delivered intervention of weekly calls for 6 more weeks from the 
providers at the Durham VA.  This intervention will be tailored to include psychological and 
behavioral activation components, consistent with what can be delivered by physical therapists.  
The third step of the ICP will consist of 6 treatment sessions over 6 weeks for those that have 
been identified as medium or high risk on the SBST.  
 
There will not be strict control of specific interventions delivered in the ICP.  However, the ICP 
incorporates interventions that align with best practice for low back pain management (i.e., non-
pharmacological pain treatment, early physical activity, risk stratification, and behaviorally 
focused intervention).  Moreover, inclusion of centrally-delivered services through the Durham 
VA will help to ameliorate current delays in VA access to services. If there is interest from 
participating sites, on-site providers will be trained to take over centrally delivered components 
after the study period ends.    
 
Pathway Procedure for the ICP 
The overall flow for the integrated care pathway is described in Figure 1, with each step 
described in more detail in the Figure legend.  A TIDier summary14 for the ICP is also included 
in Appendix II.  

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Figure 1. Overview and Summary of Integrated Care Pathway 
Figure Legend: 
1.
Patients are referred from physician to central delivery to explain the ICP and initiate onsite PT services, receive 
examination, on site treatment, and a transcutaneous electrical nerve stimulation (TENS) unit.
2.
Patients are referred for approximately 6 weeks of centrally-delivered physical activity instruction. 
3.
Patients follow up with VA PT services for re-examination.
4.
Patients complete the SBST. Patients who score ‘low risk’ are discharged to home with instructions to continue their 
physical activity program.  Patients who score ‘medium to high risk’ are referred for approximately 6 weeks of a centrally-
delivered psychologically-informed intervention. 
5.
Patients who receive psychologically-informed interventions are discharged to home upon completion. 
y
g
y

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Physical Therapy Services from Participating Sites  
The physical therapy provided in the ICP will be standardized as part of the site training 
process.  The ICP emphasizes non-pharmacological, physical pain treatment for care being 
delivered for at participating sites (Figure 1, Step 2).  Keeping with the pragmatic nature of this 
trial, the exact type of pain treatment received will vary from site to site within allowable, 
evidence based options.  For this trial that will be in the form of manual therapies and/or 
transcutaneous electronic nerve stimulation (TENS). Manual therapies are a body-based 
technique that involve application of forces to patients’ muscles, joints, and nerve related 
tissues. Each application is theoretically used to modulation pain, reduce or eliminate soft tissue 
inflammation, improve contractile and non-contractile tissue repair, extensibility, and/or stability, 
and increase range of motion for facilitation of movement and return to function. Over 200 
different forms of named manual therapies exist worldwide and are used by a number of 
healthcare professions, including chiropractors, physical therapists, osteopaths, osteopathic 
physicians, and massage therapists. Manual therapies are best defined by the description of the 
application or technique. In this trial, we will use spinal manipulation and massage as the 
manual therapies of choice.  TENS will be used as a separate modulatory element for physical 
pain treatment.  TENS is the cutaneous delivery of electronic current through electrodes, and 
has been used for pain modulation for over 50 years.  TENS is included in this proposal to 
provide patient and provider flexibility. Spinal manipulation, massage, and TENS will be applied 
as described below. 
 
Spinal Manipulation. We will consider use of a wide range of spinal manipulation techniques 
that fit an overall criterion: manipulation consists of a manual force applied to the spine that is 
accurately localized or globally applied in a single, quick and decisive movement (thrust) of 
small amplitude, following a careful positioning of the patient.  This definition includes two forms 
of spinal manipulation: Localized manipulation (e.g., short lever manipulative procedures) 
involves the intent of applying a passive or assisted movement towards one specific functional 
region (i.e., spinal unit or single joint). These techniques are occasionally termed short lever 
manipulative procedures; Generalized manipulative techniques (e.g., long lever techniques) 
involve less defined pre-positioning methods and are designed to isolate the thrust to a 
dedicated region. Force is directed through a long lever arm, which is distant from the specific 
contact.  
Massage. Massage methods involve the intentional and systematic manipulation of the soft 
tissues of the body to enhance health and healing. Multiple forms of massage techniques exist, 
and may include gliding, sliding, percussion, compression, kneading, friction, vibrating, and 
stretching. When the various forms have been compared in clinical trials, statistically significant 
differences among methods were found although the effects were very small.13  As such, 
massage methods will be described universally as having a similar effect. Specific massage 
techniques for this embedded pragmatic trial will be limited to those that are most commonly 
used in participating clinical settings, including gliding, sliding, percussion, kneading, and 
stretching.  Variation in specific technique is warranted because when the various forms have 
been compared in clinical trials, statistically significant differences among methods have been 
found but the effects were very small and don’t suggest a superior technique exists.13  
TENS. Results from TENS efficacy studies among individuals with chronic pain conditions have 
not been uniform.15-17.  However, in many of these trials TENS delivery was likely suboptimal.18  
Recent animal models have expanded our understanding of TENS mechanisms.  A key finding 
was that certain TENS frequencies activate the descending pain inhibitory system at the 
midbrain and spinal cord; including the periaqueductal gray, rostroventral medulla, and spinal 
cord dorsal horn.19-22 Moreover, TENS activates mu-opioid receptors, which are the same 
receptors responsible for pain relief through pharmacological pain management.21,23,24 In this 
embedded pragmatic trial, we will utilize TENS delivered at current evidence-based 
recommendations, which is asymmetrical biphasic alternating current at high frequency (20-

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150Hz) and high intensity (verbalized by patient as “strong but tolerable” and not 
noxious).18,25,26.  Moreover, sensory perception changes with age, meaning older adults require 
higher intensities to experience similar pain reduction as younger adults and we will ensure our 
dosing parameters adjust for Veteran age.27 
 
Home Based Treatment from Durham VA Providers. A key component of the ICP is a 
comprehensive, home-based 6-week physical activity program (Figure 1, Step 3).  This is an 
integral part of the program because physical activity is a core component of managing LBP 
over the long term.28,29  In addition, given the chronic nature of this condition, it is essential that 
individuals learn skills for continuing with a physical activity program in the absence of regular 
clinical oversight.  Therefore, this part of the program emphasizes development of skills in goal 
setting, exercise progression, and dealing with barriers and setbacks in continuing a physically 
active lifestyle, particularly in the context of CLBP.   
 
Prior research has not identified one specific physical activity program as being superior for 
individuals with LBP.  Rather, based on prior studies, LBP guidelines simply recommend that a 
physical activity program for individuals with LBP should be comprehensive and include 
stretching, strengthening, and endurance activities.28,29   Therefore the physical activity program 
of this pathway will include all of these elements.  This component of an integrated care 
pathway will be telephone or video-based coaching; this is a delivery approach we have 
employed successfully in other studies of Veterans with chronic pain conditions.30-32 Specifically, 
we will be following the protocol of a home based, telephone supported physical activity 
program that was successfully piloted by Goode et al for older adults with low back pain.33 
Risk Stratification. After completion of the 6-week program there is an opportunity for tailored 
treatment based on risk stratification by the SBST (Figure 1, Step 4).  Risk stratification will be 
completed by the on-site PT on return to clinic visit. The SBST is a simple, but effective, risk 
stratification method that can be scored quickly (summing 9 items) to derive a low, medium, or 
high risk classification.34 SBST use is consistent with cutting edge methods for identifying 
patients with LBP who are unlikely to recover unless they receive modified treatment with a 
behavioral and/or psychological focus. Furthermore, the SBST is better than or comparable to 
individual psychosocial questionnaires that have traditionally been used for establishing 
prognosis.25,35   The onsite PT will apply SBST risk stratification based after the home based 
physical activity is completed because this approach that improves prediction accuracy and 
reduces the number of participants unnecessarily identified to be in need of behaviorally 
focusedtreatment.36 Those at low risk from the SBST screen will be discharged from additional 
services, and recommended to follow up with the original referring source (Figure 1, Step 6). 
 
Those at medium to high risk will receive behaviorally focused treatment that incorporates key 
psychological principles to encourage continued activation (Figure 1, Step 5).  This integrated 
approach of combining physical and psychological treatments is appropriate for physical 
therapists to deliver, and the treatment provided will be consistent with the scope of practice for 
a physical therapist.  Indeed Drs. George and Keefe have completed such training for several 
other clinical trials involving non-psychologist providers delivering psychologically informed 
treatments.  This part of the pathway will continue with weekly calls for 6 weeks.  The overall 
goal of the tailored behavioral treatment is to reduce pain-related fear and threat associated with 
LBP, as well as to discourage long-term avoidance behavior and encourage activation.  This 
team has extensive experience with randomized and embedded pragmatic trials investigating 
the efficacy and effectiveness of combined approaches (e.g., physical therapy combined with 
pain coping skills).  The nature of the activities will change however intentionally shifting to 
graded exercise, improving self-efficacy, and enhancing pain coping skills.  This shift in 
treatment philosophy is warranted for the patients that remain medium or high risk after the 
physical activity phase.  The overall goal of this part of the ICP is to reduce the risk of continuing 

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disability from LBP while emphasizing the need for self-management.  After completing the 
behaviorally focused treatment the Veteran will be discharged from the ICP and recommended 
to follow up with the original referring source.   
2.4 
Coordinated Care Pathway  
The Coordinated Care Pathway (CCP) involves referral of patients to a pain navigator who is 
knowledgeable in current recommended treatment guidelines for low back pain. The pain 
navigator engages in a shared-decision making process with patients to determine the 
appropriate guideline supported VA service for back pain.  The pain navigator will also help to 
coordinate consultation of services with the referring physician.   
 
Pathway Procedure 
The overview of the care management pathway is described in Figure 2, with each step 
describe in more detail in the Figure Legend.  A TIDier summary14 for the CCP is also included 
in Appendix III.     

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Figure 2. Overview of the Care Management Pathway 
Figure Legend: 
1.
Patients are referred from their physician to a clinic pain navigator. Pain navigator contacts patients 
via telephone or video conference. Pain navigator and patient engage in a shared-decision making 
process to identify the appropriate VA service for patient’s low back pain.
o
Pain navigator provides information on current VA recommended guidelines for non-
pharmacologic and non-surgical pain management; as well as availability of services
o
Patient provides their services preferences
2.
Pain navigator coordinates consultation input with physician.  Patient attends service. 
3.
At the completion of service, patient either do not seek further care and are discharged to home, or 
seek further care through the pain navigator.
4.
Patients who seek further care through the pain navigator re-engage in the share-decision making 
process to identify the next appropriate VA service.  The pain navigator coordinates consultation 
input with physician, and patient attends a second service.
5.
At the completion of service, patient either do not seek further care and are discharged to home, or 
seek further care.  Those seeking further care follow up with the pain navigator who coordinates 
referral back to the physician.

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Rationale for Coordinate Care Pain Management Pathway  
VA has adopted the Stepped Care Model for Pain Management (SCM-PM)1 and this is the 
model of care that the CCP is designed to deliver. The SCM-PM is an evidence-based model 
that calls for initial assessment and management of health problems via low intensity 
interventions, delivered in the context of Patient-Aligned Care teams (VHA’s version of the 
patient-centered medical home model). Expanded Care Management in Patient Aligned Care 
Teams (PACT) is recommended as an initial approach to pain care; however, there has been 
little guidance for how PACT teams should accomplish this. Thus, the CCP will implement and 
test a direct recommendation of VA’s SCM-PM by training a pain navigator to facilitate access to 
VA and non-VA pain services. 
 
Pain Navigator. The pain navigator, a member of the PACT, will contact patients by phone or 
video within one week of referral. Using standardized protocols for assessing clinical 
appropriateness and eliciting patient preferences, pain navigators will provide information and 
guidance for patients to facilitate access to existing VA and non-VA resources for LBP care that 
is consistent with their preferences and recent practice guidelines for LBP (Figure 2, Step 2). 
Pain navigators will conduct up to a maximum of three calls with patients over a 3-month period 
depending on what is needed or recommended; with the first call to survey recommended 
services, elicit Veteran preference, align with guidelines, and initiate referrals.  The pain 
navigator will also have a role in addressing any encountered barriers to access, and encourage 
engagement and adherence with recommended services. Consistent with the SCM-PM, pain 
navigators will initiate referrals sequentially and only refer to subsequent programs or services 
(up to a maximum of 2) if the Veteran has not improved.  Veteran improvement will be based on 
two factors 1) persistent pain and/or physical limitation based on the PROMIS measures 
collected as part of the clinical pathway and 2) indication of willingness to seek additional care 
for LBP symptoms.  After 2 services without improvement the Veteran will be referred to the 
physician that initiated the CCP referral (care pathway).  
Services.  The specific services the Veterans receive in the CCP are not to be controlled by the 
pain navigator.  Instead the pain navigator will use general principles of guideline adherence 
and patient preference to coordinate care.  It is beyond the intent of this embedded pragmatic 
trial to have strict restrictions on the pain management services received (including additional 
diagnostic tests).  This is an intentional part of the design, and instead of controlling the services 
received, we will be collecting information on the type of treatments and procedures that were 
part of the care episode for low back pain.  For more details see Section 5.3 (Concomitant 
Interventions) and see Section 6.0 (Study Procedures) for the templates that will be used to 
create Health Factors that will collect specific information on patient encounters from the 
electronic medical record for those in the CCP.    
3. STUDY DESIGN 
An overview of this 4 year cluster randomized embedded pragmatic trial is presented in 
Figure 3 and SPIRIT Table37 is included in the Appendix IV.  We will compare the 
effectiveness of two care pathways for LBP.  The trial will test the central hypothesis that 
patients in the ICP will have reduced pain interference and improved physical function 
compared to patients in the CCP.  We are testing these two care pathways in a comparative 
effectiveness approach because both have the potential to deliver guideline adherent, 
biopsychosocial-oriented care but they have different implementation approaches.   

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VA primary care clinics that have agreed to have their clinical staff trained in offering 
these care pathways as standard care will be randomly assigned to one of the two care 
pathways. A cluster randomized trial (CRT) was selected because it offers the most pragmatic 
and efficient design to address our aims due to the nature of the care pathways and interest in 
assessing both short and long-term outcomes. An important consideration in a CRT is the 
optimal unit of randomization. We will designate the unit of randomization as the VA clinic 
(rather than an entire VAMC ‘site’ or ‘station’) to 1) enhance feasibility of implementation, and 2) 
improve power (higher number of clusters).  
Veteran outcomes will be collected in the EHR at baseline and at 3-months follow up 
and for a subset of Veterans, surveys will be administered at baseline with follow up points at 3, 
6, 9, and 12 months (see Section 10 - Measures and Data Collection).  The primary outcomes 
(PROMIS short forms for pain interference and physical function, 4 items each) and secondary 
outcome (PROMIS short form sleep quality) will be captured in the VA medical record by clinical 
providers using templates provided by the research team (see Section 6 - Study Procedures). 
Veteran participants (n=848) will be consented for the additional survey data collection by 
Durham VA study staff (baseline) and DCRI’s Outcomes Call Center (3, 6, 9, and 12 month 
follow-up calls).     
This trial is purposefully powered to examine treatment effect moderation for care 
strategy responses in select patient subgroups.  Many clinical trials find negligible or small 
treatment effects for LBP interventions, so identification of treatment moderators (i.e. factors 
that predict largest benefit from intervention) is important for a better understanding of how 
treatment could be administered at the patient level.  This is a newer area of emphasis in LBP 
research and there are methodological38 and statistical39 challenges to investigating treatment 
moderation.  We have mitigated many of those challenges by taking an a priori approach that 
Figure 3.  Study Design Overview  
R
Integrated Care 
Pathway 
N = 8 Clinics 
Coordinate Care 
Pathway
N = 8 Clinics
Randomization
Clinic Training and Enrollment
Follow Up 
Analysis and Dissemination
PRO Survey Capture
3, 6, 9, 12 months 
EHR Capture
3 months 
Analyses and Manuscripts 
Comparative Effectiveness
(Specific Aim 1) 
Analyses and Manuscripts
Treatment Heterogeneity
(Specific Aim 2) 
BASELINE
EHR Capture, N = 1,680
PRO Survey Capture, N=848 
Clinic Enrollment and Randomization: 
Occurs in 2 Waves
 

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focuses our treatment moderation analyses to 1) chronic vs. acute LBP and 2) previous opioid 
use vs. opioid naïve.  This is a embedded pragmatic trial so these two subgroups were selected 
for their clinical relevance (i.e. can be easily identified during routine encounters) and because 
their potential as treatment moderators has been established in the literature.  Indeed a 2015 
meta-analysis on this topic included LBP status and narcotic medication use as potential 
treatment moderators with strong statistical evidence (p < 0.05) supporting their inclusion in 
confirmatory analyses.38  We hypothesize that we will observe better outcomes from the ICP for 
patients with chronic pain and opioid exposure based on previous studies.38,40,41  Including 
planned subgroup analyses in this embedded pragmatic trial will complement the primary trial 
results by providing important information to guide decisions about optimal targeting of 
resources.  Moreover, by focusing on subgroups that have been prioritized in the scientific 
literature, these analyses also advance the field in this emerging area.    
4. SELECTION AND ENROLLMENT OF CLINICAL SITES AND PARTICIPANTS  
This study is a 4-year cluster randomized embedded pragmatic trial comparing the 
effectiveness of two care pathways for increasing non-pharmacological treatment options for 
LBP. The study target population is veterans seeking services for lower back pain in 
participating VA clinics.  There will be selection of clinical sites and participants for this trial.   
 
Clinical Site Selection  
On May 16th we met with VISN6 leadership to distribute an update on the AIM-Back trial and 
being the process of recruiting interested clinical sites.  Formal site agreements will be pursued 
once the study protocol is  finalized (Appendix I).   
 
Unit of randomization: VA primary care clinics.  
 
Sample size: 16 clinics (8 clinics randomized to each care pathway). 
 
Clinic eligibility: 
• 
Volunteer and return signed clinic participation agreement 
• 
Availability of clinical personnel willing to deliver the treatment interventions (in either 
arm). 
• 
Staff and location need to be distinct from other enrolled clinics. 
• 
Clinics can have a variable number of providers, but together meet criteria for range of 
monthly visits for LBP 
4.1 
Participant Inclusion Criteria 
At the level of the individual, participant eligibility criteria are intentionally broad in keeping with 
the pragmatic nature of this trial.  Eligibility criteria will be applied equally to and are appropriate 
for individuals seeking care at any of the clinical sites.  Site training will include instruction in the 
referral criteria so that providers have consistency in the selection of participants for the care 
pathways (see below).  Our intent is to: 1) examine the care pathways in the way they would be 
used in clinical practice; and 2) maximize diversity and the potential to generalize the findings 
from this trial.   
 
Referral Criteria (part of site training and used by providers for pathway determination)  
1. LBP that is localized or radiating  
o Localized = symptoms reported in the T12 to S5 region only, occurring unilaterally 
or bilaterally  

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o Radiating = localized symptoms reported in the T12 to S5 region, occurring 
unilaterally or bilaterally and radiating symptoms to the buttocks, thigh, or lower 
leg 
2. LBP that is appropriate for conservative care  
o No history of recent spinal trauma or surgery (i.e. past 3 months)   
o No signs or symptoms suggestive of spinal fracture, tumor, or infection  
 
Specific inclusion criteria for inclusion in the analyses are listed below. 
Inclusion Criteria (must meet all) 
1. Age >= 18 
2. Seeking care for LBP with or without radiating symptoms from a participating VA primary 
care clinic  
3. Provider determines LBP is appropriate for conservative management   
4. Referred to integrated ICP pathway or CCP pathway by participating clinic provider 
 
4.2 
Participant Exclusion Criteria 
Narrower eligibility criteria would exclude a significant number of patients with LBP resulting in 
limited application of examined care pathway models. Some patients will not meet clinical 
criteria for all treatments within each pathway; however, they will be included in the evaluation to 
be consistent with our pragmatic goals of determining the average treatment effect of each arm 
for patients with LBP when receiving routine clinical care.  All adult subjects (not referred for 
hospice or palliative care) that are enrolled in a participating VA primary care clinic and 
are referred to one of the LBP pathways will be eligible for the main analysis. 
Exclusion Criteria (if meet any) 
1. Receiving or referred for hospice/ palliative care (defined by encounter codes and CPRS 
consults) 
2. No documented phone number in the electronic health record. 
4.3 
Study Enrollment Procedures for Outcome Collection 
Enrollment procedures. We anticipate total sample size of 1,680 Veterans for the 
administrative sample (main analysis). For these participants, data will be obtained from VA 
administrative and electronic health records. 
We will recruit a subset of Veterans (n=848) to participate in a series of telephone interviews. 
The selection of this subset is described in the subsequent section (Screening, Informed 
Consent, Baseline Data Collection). Because these participants will be asked to provide 
additional information over and above what is collected and stored in the electronic health 
record as part of routine clinical care, we will seek informed consent for participation in this 
portion of the study, using the following procedures. The additional inclusion/exclusion criteria 
for the telephone subset are: 
 
Inclusion Criteria for Telephone Survey Subset (must meet all) 
1. Valid phone number in medical record 
2. Able and willing to provide informed consent 
 
Exclusion Criteria for Telephone Survey Subset (if meet any) 

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1. Currently in institutional care (nursing home or hospital).  
2. Cognitive impairment or dementia (identified via ICD diagnosis codes or PCP note in 
previous 2 years) or lack decision-making capacity, documented in the medical record.  
3. Serious mental illness defined as diagnosis of schizophrenia, bipolar disorder, 
psychiatric hospitalization in the previous year or current high-risk suicide flag in their 
CPRS medical record.  
4. Unable to communicate on the telephone, or no telephone access for duration of study 
 
Opt-out letter and enrollment over the telephone. At the beginning of the study, centrally 
located Durham VA study staff will generate an opt-out letter signed by the research team that 
will be mailed to all potentially eligible patients enrolled in participating VA primary care clinics. 
The letter will describe the study and include an “opt-out” phone number if they do not wish to 
be contacted further. We will also include opt-out information on printed clinical program 
brochures that providers give patients in clinic at the time of referral.  
We have opted not to enroll Veterans in person because phone interviews improve feasibility 
given the number of (n = 16 clinics), their expected geographic dispersion, and the overall 
number of participants that will need to provide consent for survey contact (n = 848). In addition, 
enrolling by phone is least burdensome for patients and allows us to reach patients whose clinic 
visit may have occurred on a weekend or during evening hours. All VAMC primary care clinics 
now offer some expanded hours. 
Screening, Informed Consent, Baseline Data Collection. Durham VA study staff will conduct 
a biweekly data pull that identifies Veterans that have been referred to the pathway at enrolled 
clinics who meet eligibility criteria. We will randomly sort eligible participants, stratified by clinic, 
and the RAs will recruit from this list for the Telephone Survey Subset. Before contacting each 
patient for enrollment, RAs will perform targeted chart review to confirm eligibility and then 
contact Veterans to screen for additional exclusion criteria not always identified in the medical 
record (e.g. hearing impairment or hospice referral) and ask them if they wish to participate. 
Because the study is entirely telephone based, waiver of written informed consent has been 
granted by the Durham VAMC IRB. After obtaining verbal informed consent, the Durham VA RA 
will collect baseline survey data from all study participants. Study staff will attempt to contact 
Veterans for enrollment within 2-3 days of the data pull date and make up to 10 attempts to 
contact each potentially eligible subject. 
Telephone Surveys Follow-up.  
Survey participants will have provided verbal informed consent prior to baseline survey 
collection to allow for additional contact from the Duke Outcomes Call Center for the follow-up 
surveys at 3,6,9 and 12 months.  
Data collected via telephone interviews will complement the data obtained via EHR with patient-
reported data across multiple domains of pain and associated co-morbidities. These data will 
also provide rich information about response trajectories and suggest areas to target future EHR 
data capture methods. This approach ensures the trial will build capacity for conducting large-
scale pragmatic clinic trials with the VA health care system.   
 

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5. IMPLEMENTATION OF CARE PATHWAYS  
VA clinics that have agreed to have their clinical staff trained in offering these care pathways as 
standard care will be randomly assigned to one of the two care pathways. The manual for 
training materials used for participating VA clinics is included in Appendix V.  VA clinics 
implementing these back pain care pathways are not engaged in research because both 
pathways involve different ways of providing standard of care treatment.  Employees at clinical 
sites that implement the back pain care pathways will participate in educational training for 
delivering the treatment as part of standard care, clinical program-related duties only.   
 
AIM-Back will employ implementation facilitators to work with clinics to implement 
and maintain their care pathways. AIM-Back facilitators will work directly with a Point 
of Contact selected by each site to develop procedures for keeping the care 
pathways and referral procedures top of mind for referring providers, using existing 
infrastructure at each clinic (e.g. staff meetings).  Employees delivering the clinical treatment will 
not be directly involved in any research related procedures (e.g. follow up survey collection over 
the phone).  To assist each site in implementing the care pathways we will collect data and 
provide reports to be used for process improvement. These will include both quantitative (e.g. 
number of eligible patients, number of referrals, etc) and qualitative data collected from 
interviews with participating providers (e.g. exploring referral process and patient response to 
care pathways). 
5.1 
Qualitative Data Collection    
In-depth, semi-structured, individual telephone interviews (~20-30 minutes each) with be 
conducted with a sample of the participating, referring providers.  We will purposefully 
sample approximately 2 referring providers from each clinic as a function of low/high 
adoption as evidenced by number of referrals at 2.5 to 3 months (based on clinic start 
dates).  Interviews will be conducted as close as possible to the 3-month time frame (+/- 
2 weeks to allow for scheduling). A structured form for notetaking will be utilized in order 
to facilitate rapid qualitative analysis. Information obtained will be used to create case 
memos (case study qualitative design), which will be fed back to the clinics and 
triangulated/supplemented with process improvement notes from the facilitator. We will 
target providing this feedback to the clinics by around the halfway point of the 9 months 
(i.e., 4.5 months). Information obtained will also inform the next starting clinics with an 
evaluation across all cases (multiple case study design) to be conducted at the 
conclusion of the active study/pathway period. The interview guide will be informed by 
the Consolidated Framework for Implementation Framework (CFIR)42 and include in-
depth, descriptive questions on barriers and facilitators at multiple levels (i.e., provider, 
clinic, facility, and patient) from the perception of the referring providers.  All qualitative 
data will be used for quality improvement purposes (i.e. will not be considered human 
subjects research).                      
 
5.2 
Concomitant Interventions  
We have taken steps to minimize the risk of cross-contamination through our choice of study 
design and by imposing restrictions on clinic participation.  That is, clinics must be located at 
geographically distinct locations, rather than on the same campus. We will measure and report 
the number of patients with referrals to both LBP care pathways.  Furthermore, evidence of 
concomitant diagnostic testing and treatments received outside of the care pathways will be 

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monitored via the VA electronic record for both LBP care pathways.  Finally, we will be 
implementing templates (Section 6.0 Study Procedures) to capture key study outcomes as 
health factors and also collecting health care utilization data from both care pathways to track all 
intervention usage and adherence to intervention.  Because this is a embedded pragmatic trial 
we can’t limit use of concomitant interventions, but we will be able to track usage rates and 
compare across the two care pathways.    
 
5.2 
Adherence Assessment  
We will examine “adherence” among all patients referred to one of the clinical pathways. We 
define “adherence” according to patient participation in planned sessions with intervention team 
personnel (telehealth or in-person) in either the ICP or the CCP depending on participating 
clinic. Data for participation/adherence to ICP sessions will be captured in progress notes 
entered into the EHR (see Appendix) and completion of referred services to CCP will be 
captured in the EHR. The number of planned sessions will vary between and within arms (e.g. 
depending on response to 1st service in CCP and depending on risk stratification in ICP); 
therefore, to define an adherence measure that may apply to both arms for descriptive purposes 
we will a priori define adherence as follows: 1) non-adherent – attended no planned sessions 1) 
partially adherent – attended some, but not all planned sessions 3) attended all planned 
sessions. 
 
We are defining adherence this way a priori because the number of referrals/sessions for 
Veterans to adhere to can vary greatly depending on the intervention.  For the ICP intervention, 
the number of referrals or sessions to adhere to depend on risk stratification using the SBST (8 
for low-risk veterans and 14 for high risk veterans).  For Veterans in the CCP arm, the maximum 
number of referrals to adhere to can range from 1 to 3 depending on what referrals (if any) are 
made by the Pain Navigator (Table 3).  
 
Our a priori three-level categorization for adherence is equitable between arms in the upper and 
lower categories, but the middle category could be very heterogeneous and not informative. 
Therefore, we will describe adherence in both care pathways separately in order to identify 
patient characteristics potentially associated with program participation and improved pain 
outcomes. We will not test for differences in adherence between pathways as our goal is to gain 
insight into where to target clinical programs and focus efforts to improve access to and patient 
engagement with non-pharmacologic pain services.  Depending on the distribution of the 
number of sessions in each pathway, we will explore additional multi-level variables that may be 
more informative within arms.  Within ICP and risk groups, we may be able to use more granular 
definitions (e.g. continuous measures) for examining the impact of adherence on outcomes 
within treatment arm and/or risk group.  
 
The structure of the adherence variable for Aim 2 analyses will depend on the empirical data 
distribution to determine adherence categories for each arm.  For the CCP arm the a priori 
definition above may be reasonable, however for the ICP arm more granular categories by risk 
groups should be possible (see Table 3).    
 
Data Collection for Adherence  
 
For both CCP and ICP, adherence outcomes in Table 3 for each participant will be captured in 
the EHR via referral consults to pathways and health factor data in EHR templates used by 

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clinic personnel in each of the pathways (see CCP and ICP templates in Appendix VI and VII for 
details). 
 
 
1.  For the CCP pain navigator, the denominator can range from 1 to 3 so percentage of 
adherence for patients is either (0 or 100%), (50% or 100%) or (33%, 66% or 100%)  
a. Patient is referred to the navigator - patient can adhere or not adhere to that 
referral  
b. Pain navigator may refer to service - patient can adhere or not adhere to that 
referral 
2. Patient not satisfied with that referral so gets a second referral – patient can adhere or 
not adhere to that referralor ICP low risk patient, the denominator is 8 
a. Patient is referred to PT – patient can adhere or not adhere to that referral  
b. Home central delivery – 6 weekly sessions  
c. PT follow-up – patient can adhere or not adhere to that follow-up  
3. For ICP high risk patient, the denominator is 14  
a. Patient is referred to PT – patient can adhere or not adhere to that referral  
b. Home central delivery – 6 weekly sessions  
c. PT follow-up – patient can adhere or not adhere to that follow-up  
d. CBT phone sessions – 6 weekly session 
 
 
 
 
 
Table 3.  Adherence Metrics and Definitions for Each Care Pathway 
 
Intervention 
Sessions 
Adhered 
(Yes/No) 
Adherence 
outcome 
Notes 
CCP 
Initial referral 
only 
Yes 
1/1 
 
 
 
No 
0/1 
 
 
 
 
 
 
 
Referral for 1 
service only  
Yes 
2/2 
 
 
 
No 
1/2 
 
 
 
 
 
 
 
Referral for 2nd 
service  
Yes 
2/3 or 3/3 
May or may  not 
have adhered to 
1st service 
referral  
 
 
No 
1/3 of 2/3 
May or may  not 
have adhered to 
1st service 
referral 
 
 
 
 
 
ICP 
Initial referral to 
1st PT visit 
Yes 
1/8 
 

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No 
0/8 
 
 
 
 
 
 
 
Home-based 
delivery sessions  
Yes 
2/8 to 7/8 
May not adhere 
to all 6 sessions; 
to get here had 
to adhere to 1 
(initial referral) 
 
 
No 
1/8 
Adhere to initial 
referral but did 
not complete any 
home based 
sessions 
 
 
 
 
 
 
2nd PT visit 
Yes 
1/8 to 8/8 
 
 
 
No 
1/8 to 7/8 
If do not adhere 
to 2nd PT visit do 
not know risk 
group 
 
 
 
 
 
High risk group 
only 
CBT telehealth 
delivery sessions  
Yes 
3/14 to 8/14 
May not adhere 
to all 6 sessions; 
to get here had 
to adhere to 2 
initial referral 
and 1st PT visit  
 
 
No 
2/14 to 8/14 
 
6. STUDY PROCEDURES  
An overview of the Study Procedures is included in Appendix IV (SPIRIT Table37).  This is 
embedded pragmatic trial that involves providers inputting data collected during routine clinical 
encounters for LBP in VA clinics that have participated in the educational sessions for delivering 
the care pathways.  These clinical providers are not research staff.  These EHR templates for 
data collection will allow for retrieval of data from the Corporate Data Warehouse so that study 
related analyses can be performed.  
 
6.1 
EHR Data Collection Templates  
As our primary outcomes are collected by clinical providers in the EHR, we will have study 
procedures in place to help providers with timing of outcome ascertainment (see outcome 
ascertainment study flow diagram in Figure 4). For baseline outcome assessments, biweekly 
reports will be generated for initial intervention contact and baseline EHR outcome collection by 
the Pain Navigator in the CCP arm and ICP centralized study personnel.  Similarly, biweekly 
reports will be generated with a list of eligible patients for the 3-month assessment and provided 
to CCP Pain Navigator or ICP centralized personnel. The study team will monitor outcome 
ascertainment timing at each participating clinical site to trouble-shoot any problems or issues to 

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circumvent loss of follow-data. Interim EHR data will be collected during routine intervention 
contact       
 
 
 
 
 
Figure 4. AIM-Back Procedure for Ascertainment of Primary Endpoint 
 
 
Theinformation collected is also summarized below in Tables 4 and 5, and the template 
documents are included as Appendices VI and VII with this protocol.  
6.1.1 Integrated Care Pathway 
Table 4. Summary of Variable Fields Collected by Providers for Integrated Care Pathway  
Template  
Clinical and 
adherence 
variables 
PROMIS* 
Risk 
Stratify 
Provider Action 
Central 
Delivery Initial 
Phone Call 
Data Collection 
Template 
CDC Pain  
NIH Back Pain 
Adherence 
Physical Function  
Pain Interference  
Sleep Quality 
Start Back 
Screen 
Initiate PT Evaluation 
Describe ICP intervention 
Initial intervention contact 
Baseline EHR outcome collection 
(CCP or ICP Personnel) 
Do not end up in study? 
-refuse/never able to reach 
Assigned Care Pathway 
Delivered 
Biweekly reports for 3-month 
primary outcome assessment 
EHR primary outcome assessment 
(CCP or ICP Personnel) 
CONSULT generated to study 
trial arm 
Biweekly report with list of 
eligible CONSULTS 
Do not end up in study? 
-discontinued 
-cancelled  

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ICP-PT 
Intervention 
Template Visit  
 
CDC Pain  
NIH Back Pain 
Adherence 
  
Physical Function  
Pain Interference  
Sleep Quality  
Start Back 
Screen 
Pain Modulation 
Education  
Central Delivery Referral 
 
Central 
Delivery 
Physical 
Activity Phone 
Call Template 
 
Adherence 
 
 
Review and Modify Home 
Exercise Program 
Goal Setting and Action 
Planning  
 
 
Educate on Pace Setting 
Skills 
ICP-PT 
Intervention 
Follow-up Visit 
CDC Pain  
NIH Back Pain 
Adherence 
Physical Function  
Pain Interference  
Sleep Quality 
Start Back 
Screen 
Pain Modulation 
Education  
Low Risk - Discharge 
Med/High Risk - Referral  
Central 
Delivery CBT 
Medium / High 
Risk 
Intervention 
Phone Call 
Template  
Adherence 
 
 
Pain Coping Skills 
Behavioral Activities   
Central 
Delivery 3-
month follow-
up Phone Call 
Data 
Collection 
Template 
 
 
CDC Pain  
NIH Back Pain 
Adherence 
Physical Function  
Pain Interference  
Sleep Quality 
 
 
Key - * = primary outcome collection through the health factor via the electronic health record  
6.1.2 Coordinated Care Pathway 
Table 5. Summary of Variable Fields Collected by Pain Navigator  
Template  
Clinical and 
Adherence 
PROMIS 
Navigator Action 
Pain 
Navigator 
Care 
Pathway 
Initiation and 
Baseline Data 
Collection 
Template 
 
CDC Pain 
NIH Back Pain 
Adherence 
 
Physical Function  
Pain Interference  
Sleep Quality  
Service Referral 1  
Guideline Review 
Patient Preferences 
Pain 
Navigator 
Care 
Pathway 
 
Adherence 
 
Service Referral 2  
Guideline Review  
Patient Preferences 

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Update Call 
Template  
 
Pain 
Navigator 
Care 
Pathway 3-
month 
Follow-up 
Template
 
 
CDC Pain 
NIH Back Pain 
Adherence 
Physical Function  
Pain Interference  
Sleep Quality 
Services Received Summary 
Referral to Initial Provider 
Pathway 
Completion/Discharge 
Key - * = primary outcome collection through the health factor via the electronic health record  
6.2 
VA Corporate Data Warehouse Collection  
Collection from VA Corporate Data Warehouse will include: 
 
Medication use.  Outpatient and inpatient files from the VA Corporate Data Warehouse will be 
used to evaluate all visit data and associated diagnosis codes. Pharmacy Benefits Management 
(PBM) outpatient records will be used to define medication outcomes. PBM includes medication 
information including date dispensed, VA product name and VA drug class, generic drug name, 
national drug code, prescriber identifiers, and quantity and days’ supply dispensed 
 
Imaging, providers, and procedures. We will measure utilization of LBP imaging, provider 
visits, and selected procedures according to procedures employed in prior studies. 43-46 
Following processes used in prior studies from Drs. Goode46 and George,43 we will use ICD 
codes to classify diagnostic/anatomical location and CPT codes to classify resource use within 
12 months of referral to either LBP care pathway.  For resource use we will measure and report 
imaging (total number of imaging studies of the lumbar spine region including plain radiographs, 
magnetic resonance imaging (MRIs), and computed tomography (CT) studies), provider visits 
(back pain and non-back associated), procedures (epidural steroid injection, facet injection, and 
radio frequency ablation), surgery (fusions, discectomy, laminectomy, and mild procedures).  
 
ED visits and Pain Related ED Visits. Visits for back pain related disorders to the emergency 
department are common (i.e., 2.6 million visits per year) in the U.S.47 We will measure ED visits 
for low back pain and general pain (any type) to the VA and non-VA facilities using the VA 
Corporate Data Warehouse (CDW) and Non-VA fee or ICD codes at 12-months since 
enrollment. Dr. Hastings and her team have validated strategies for identifying ED visits (both 
VA delivered and VA-financed ED care) in national VA administrative data and assigning 
reasons for visits using ICD codes.48 A summary of measures, definitions, data sources and 
time points is provided in Section 10. 
 
6.3 
Blinding 
Blinding 
Given the pragmatic design, participants and treating providers will not be blinded to the care 
pathway. Table 6 below summarizes blinding status for various study team members and also 
treating providers.  Treating providers delivering the clinical pathways at a clinic and the Veteran 
patients in that pathway have no knowledge or training on the comparison pathway being 
delivered at other clinics as part of this study. Treating providers entering health factor data in 
the EHR will not be blinded. However, survey outcome assessors (RA conducting telephone 

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surveys) will be blinded to care pathway received. Study statisticians cannot be blinded to clinic 
randomization arm as they will be monitoring data collected in the EHR to track study flow, 
provide feedback to clinics and identify barriers or problems.  Because the data entered in the 
EHR is different due to the nature of each of the interventions, it is not possible for study 
statisticians to be blinded in the conduct of this study.  Study statisticians will be generating the 
randomization tables using a covariate constrained randomization and provide a report to inform 
clinics of their randomization arm.  
 
 
Table 6.  Blinding Summary for AIM-Back Trial   
Study 
personnel 
Clinic level 
randomization 
blinding status 
Clinic level blinding 
status justification  
Individual 
patient level 
data access 
Individual patient level data 
access notes 
PIs 
Unblinded 
Site recruitment 
and engagement 
role, 
troubleshooting 
barriers to clinical 
intervention 
delivery of 
programs; 
management of 
centralized 
intervention 
delivery 
No 
Access to aggregated patient 
data presented in reports for 
tracking and troubleshooting   
Research 
coordinator 
Unblinded 
Site recruitment 
and engagement 
and monitoring of 
delivery of clinical 
intervention 
No 
Access to aggregated patient 
data presented in reports for 
tracking and troubleshooting   
VA research 
assistant 
Blinded 
 
Yes 
Administering patient 
surveys 
DCRI 
research 
assistants 
Blinded 
 
Yes 
Administering patient 
surveys 
PhD 
Statistician 
Unblinded 
Involved in 
monitoring data in 
EHR including 
assessing targeted 
sample size goals; 
conducting and 
verifying covariate 
constrained 
randomization  
Yes 
Access intermittently to 
troubleshoot any problems 
with recruitment,  data 
collection and data quality 

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Masters 
Statistician 
 
Unblinded 
Involved in 
extracting and 
monitoring data 
from EHR and 
developing reports; 
conducting and 
verifying covariate 
constrained 
randomization 
Yes 
Ongoing access to extract 
and monitor data from EHR 
and/or patient surveys 
SQL 
programmer 
Unblinded 
Involved in 
extracting data 
from EHR and 
developing reports 
to be used for 
monitoring 
recruitment, 
adherence, and 
data quality  
Yes 
Ongoing access to extract 
and monitor data from EHR 
and/or patient surveys 
 
7. SAFETY ASSESSMENTS  
The protocol is currently approved by the Duke IRB and Durham VA. Study activities requiring 
individual-level consent involve survey-based assessments only. Other research activities 
involve data collection from the EHR only; thus, this study has been deemed minimal risk study 
by the local IRB’s.   
7.1 
Adverse Events and Serious Adverse Events  
Because this study is collecting standard of care information, and contact with the participants 
only involves telephone survey-based assessments, this is considered a minimal risk study. 
There is no investigational drug or device, and all data collected through EHR records are being 
collected through routine clinical visits as part of standard care.  
 
A Data and Safety Monitoring Board (DSMB) will be appointed by NCCIH to review study 
progress, assess the adequacy of ongoing enrollment & site performance, ensure adequacy of 
data acquisition & protocol adherence and evaluate overall safety throughout trial 
implementation.  The DSMB will meet at least annually after trial initiation. A DSMB Charter 
Document outlining the operating guidelines for the committee, the frequency of planned 
meetings and the specific data presentation format will be agreed upon during the initial meeting 
of the DSMB. Study reports will be created by the study data center, following a standardized 
format, as directed by the DSMB. The DSMB will report directly to NCCIH.   
 
The PIs will report any serious, unexpected, and study-related adverse event or unanticipated 
problem to the local IRB and the DSMB within the time frame specified by current VHA and 
institution requirements. Details of the monitoring plan and approach are in the Appendix XI.   

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7.2 
Safety Monitoring  
Because this is collecting standard of care information, and contact with the participants only 
involves telephone survey-based assessments, this is considered a minimal risk study. There is 
no investigational drug or device, and all data collected through EMR records are considered 
standard of care data.  
The DSMB will be implemented to review our research procedures and operating procedures 
before initiating the study and to ensure the data collection and safety-monitoring are implanted 
while the study is ongoing.  The DSMB will also be involved with reporting of any adverse 
events that may occur, and will make the determination of whether study stoppage is indicated.  
Currently we do not have any interim analyses planned for this proposal, but we will pursue this 
option if it is indicated by the DSMB.  The DSMB will meet at least annually either in person or 
on teleconference, and will meet more frequently if circumstances warrant.  For example, in the 
situation when multiple adverse events may merit a reconsideration of the risk to benefit ratio for 
this study.  The DSMB will likely consist of 3-5 individuals with the appropriate expertise to 
review this study, but who are not directly involved with its operation and are not considered as 
prior collaborators with this research team.  The minutes and executive summary of each DSMB 
meeting will be submitted to the NCCIH, the NIH Pain Management Work Group and the local 
IRB’s involved with this trial.  
8. CLINIC DISCONTINUATION  
While our goal is to not have any clinics discontinue, clinic discontinuation could occur by a 
clinic informing us that they were dropping out after randomization but before training and rollout 
of pathways or after rollout of pathways or some other unplanned circumstance. It is important 
to note that our design allows for additional sites to be added in the 2nd round of cluster 
randomization if site(s) from the first round discontinue or have lower than expected recruitment 
rates. This is described in more detail in Section 9 (Statistical Considerations).   
 
One of the eligibility criteria for clinics is that the volume of back patients seen on a weekly basis 
is on average 8 -12 so that over a 6-month period assuming a 50% referral rate (4-6 referred 
per week) clinics can meet recruitment goal of 105 Veterans referred to their pathway; it may 
take clinics with smaller patient volumes or lower referral rates longer to enroll and weekly 
referrals could vary from 2 to 4 per week and we can still meet recruitment goals on our 
timeline.   
 
Given that this is a embedded pragmatic trial and “enrollment” is controlled by referrals from 
primary care providers to the clinics randomized pathway either CCP or ICP, the study team will 
monitor care pathway volume monthly at each participating clinical site.  The goal to monitoring 
pathway volume will be for the study team to trouble-shoot problems to help clinics increase 
pathway volume.  Over the first couple of quarters of an enrollment period at a clinic we will 
review number of referrals with clinics to make sure meeting goals and to trouble-shoot any 
problems or issues.  If it appears that lower than expected volume is occurring mitigating steps 
will include meeting with site leaders to review care pathway procedures, trouble-shoot, and 
enhance education outreach for referring providers.  At the time that we begin enrolling block 2 
clinics, we will add additional clinics if any has dropped out in block 1 and we will examine 
recruitment in the clinics in block 1 and determine whether we need to enroll and randomize 
additional clinics in block 2 to compensate for low recruitment (below target of 105 per clinic) at 
any of the block 1 clinics. The blocked covariate constrained randomization balances covariates 
within and across blocks. We will use any information from the enrollment process of the 10 
clinics in block 1 to inform and improve the enrollment process for the set of clinics for block 2.  

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We have a solid plan for dropout of a clinic or low recruitment in block 1 that maintains the 
randomization and balance of covariates with the ability to add clinics to block 2 before the block 
2 randomization.   
 
To guard against drop out of clinics from block 2 we plan to add 2 reserve sites to the 
block 2 wave of randomization to use in case a clinic should drop out of block 2.  We 
have adjusted the block sizes to have 10 clinics randomized in block 1 and have 8 clinics in 
block 2 (if no clinics drop out in block 1) which include 2 reserve clinics. Through the design 
process for this trial we have increased the number of clinics from 12 to 16 in part to 
provide a safeguard for the potential drop out of a clinic and still be able to conduct a 
successful trial (see Table 7 below that has effect sizes for 12 clinics with same number 
of patients per clinic as we targeting for 16 clinics and for 16 clinics with smaller number 
of patients per clinic). 
 
Table 7.  Sample Size Table for AIM-Back 
   
Number of 
clinics per 
condition 
Number of 
patients per 
clinic needed 
at post-
intervention 
follow-up/ 
Total N 
Df for 
baseline 
covariate 
adjustment 
Minimum 
Detectable 
Difference 
(Effect size) 
 
ICC=0.01 
Minimum 
Detectable 
Difference 
(Effect size) 
 
ICC=0.02 
Minimum 
Detectable 
Difference 
(Effect size) 
 
ICC=0.05 
Number 
needed at 
baseline with 
20% attrition 
per clinic/ 
Total Nb 
6 
42/N=504 
5 
2 
0.49 
0.44 
0.56 
0.50 
0.72 
0.65 
53/ Nb=636 
6 
84/N=1008 
5 
2 
0.40 
0.35 
0.47 
0.42 
0.66 
0.59 
105/ Nb=1260 
8 
32/N=512 
5 
2 
0.41 
0.40 
0.46 
0.44 
0.57 
0.55 
40/ Nb=640 
8 
63/N=1008 
5 
2 
0.32 
0.31 
0.38 
0.37 
0.52 
0.50 
79/ Nb=1264 
8 
42/N=672 
5 
2 
0.37 
0.36 
0.42 
0.41 
0.54 
0.53 
53/ Nb=848 
8 
84/N=1344 
5 
2 
0.30 
0.29 
0.36 
0.35 
0.50 
0.49 
105/ 
Nb=1680 
 
9. STATISTICAL CONSIDERATIONS  
9.1 
General Design Issues  
This study will be a longitudinal cluster randomized trial conducted at 16 VA clinics. The “clinics” 
must be geographically distinct with no overlap in staffing. A summary of study measures, with 
their associated definition, data source, and time interval is provided above in Section 10 (Data 
Collection and Measures). Outcomes derived from VA EHR data (for example utilization and 
pharmacy data, as well as health factor data obtained through data capture tools designed and 
implemented for this study) will be obtained for the larger administrative sample (n=1680). 
Outcomes from telephone administered surveys will be available on approximately half of 
participants (n=848), who are consented to participate in enhanced survey data collection. 

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Study measures were selected to be patient-centered and consistent with recent 
recommendations from the NIH Task Force on Research Standards for Chronic Back Pain, and 
relevant to Veteran’s health and VHA.49 
 
9.2 
Sample Size and Randomization 
In Table 8 below we present a range of minimum detectable effect size differences for the 
primary outcomes of Pain Interference or Function Scores for both the administrative 
sample (N=84 per clinic) and survey sample (N=42 per clinic) for 16 clinics (8 clinics 
randomized to each arm) for Aim 1.  Sample size calculations for the cluster randomized 
design were based on the net difference between the two conditions across baseline and 
3-months follow-up.50   We assumed over time correlations of 0.50 for both patients (based 
on data from the Goode et al. pilot study33 and summary data available for Durham VA 
clinics, intraclass correlation coefficients (ICC) of 0.01, 0.02, and 0.05 to account for clinic 
clustering, and also adjusted for the potential group-level randomization of up to 4 
stratification variables as baseline covariate adjustments where we conservatively 
assumed no reduction in either group or subject level variance components.  For all 
calculations, the type-I error is 2.5% to account for the multiple primary outcomes and 
power is conservatively assumed to be 90% to guard against deviations from assumptions. 
The number needed at baseline (Nb) is based on an attrition rate of 20%. Note in the below 
Table 4 that the scenarios above lead to having adequate power to detect a medium effect size 
for the primary outcomes for both the administrative and survey samples. 
  
Table 8. Minimum detectable effect size differences for 90% power, alpha of 0.025 and ICC 
of 0.01, 0.02, and 0.05 for administrative outcome (n=84 per clinic) and survey outcome 
(n=42 per clinic)  
Number of 
clinics per 
condition 
Number of 
patients per 
clinic needed 
at post-
intervention 
follow-up 
(Total N) 
Minimum 
Detectable 
Effect Size 
Difference 
ICC=0.01 
Minimum 
Detectable 
Effect Size 
Difference 
ICC=0.02 
Minimum 
Detectable 
Effect Size 
Difference 
ICC=0.05 
Number of 
patients per 
clinic needed 
at baseline 
with 20% 
attrition (Total 
Nb) 
8 
42 (N=672) 
0.37 
0.42 
0.55 
53 (Nb=848) 
8 
84 (N=1344) 
0.30 
0.36 
0.50 
105 (Nb=1680) 
 
The standardized effect sizes51 that we are powered to detect range from 0.30 to 0.50 for the 
primary outcomes on the administrative sample. This range maps to differences of 
approximately 2.4 to 5.0 points in the PROMIS Pain Interference score between arms assuming 
standard deviations in the range found in the pilot study from Goode et al.33 These magnitude of 
differences have been reported to be clinically relevant.52 Similarly for the survey sample, the 
range of effect size differences we can detect map to differences of approximately 3.0 to 5.5 
points between arms. 
 
For AIM 2, the subgroup analyses of the primary outcomes in the administrative sample, if 
we assume an even distribution of a binary moderator (e.g. opioid use), our effective 
sample size for detection of moderation is a quarter that for the main effect analysis 
yielding an effective sample size of n=336 (21 per clinic).53 For the moderator interaction 
effect, we can detect medium to large effect size differences over a range of assumptions 
(Table 9 below), which allows for prudent exploration of treatment moderation. 
 

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Table 9. Minimum detectable effect size differences by a binary moderator for 90% power, 
alpha of 0.025 and ICC of 0.01, 0.02, and 0.05 for administrative sample. 
 
Number of 
clinics per 
condition 
Number of 
patients per 
clinic needed 
at post-
intervention 
follow-up 
(Total N) 
Minimum 
Detectable 
Effect Size 
Difference 
ICC=0.01 
Minimum 
Detectable 
Effect Size 
Difference 
ICC=0.02 
Minimum 
Detectable 
Effect Size 
Difference 
ICC=0.05 
Number of 
patients per 
clinic needed 
at baseline 
with 20% 
attrition (Total 
Nb) 
8 
21 (N=336) 
0.48 
0.53 
0.63 
27 (Nb=432) 
 
9.2.1 Treatment Assignment Procedures 
In this study, randomization occurs at the clinic (i.e., the cluster) level and we plan on 
conducting a covariate constrained randomization2-4 with the following clinic level covariates 
assessed prior to randomization: 1) average pain scale scores of LBP patients at clinic, 2) 
average level of opioid exposure of LBP patients at clinic, 3) number of participating primary 
care providers at clinic, 4) clinic location (main medical center/community clinic) and 5) average 
age of LBP patients at clinic. These characteristics were chosen to represent factors likely to be 
associated with baseline differences in patient population that may affect primary outcomes. 
However, the exact number of covariates we use will depend on the quality and distribution of 
these covariates across the 16 clinics that we enroll.  For example, if all the clinics we enroll are 
community clinics, then we would drop the clinic location covariate in the randomization.  
Currently, throughout the VA, general pain scale scores (rate pain on a scale from 1 to 10) are 
being collected for all primary care visits and stored in administrative data. Our plan will be to 
use these data, averaging the pain scale scores of LBP Veterans at each clinic over a 3 to 6-
month time period prior to clinic enrollment. For Durham primary care clinics, we found that pain 
scores were collected at over 95% of primary care visits for lower back pain over a one-year 
time period.  From the Goode et al. pilot study33 of Veterans with back pain (n=50), we found 
that correlation of pain scale scores to PROMIS pain interference at baseline was approximately 
0.55, a reasonably strong correlation. For the opioid exposure covariate, our plan is to apply the 
PMC3 opioid exposure definition to LBP patients at clinics over a 3 to 6-month period prior to 
clinic enrollment and then use the proportion of patients that meet the opioid exposure definition 
as the average level of opioid exposure for the clinic. The number of participating (referring) 
providers at a clinic will be used as an indication of size of clinic (volume of patients served). For 
the age of LBP patients, we will use age that is available in the electronic health record and 
average the age of Veterans with LBP visits to the clinic over the 3 to 6-month time period prior 
to clinic enrollment.   
 
In planning for the UH3, we have determined that we cannot roll out the interventions for all 16 
clinics at the same time due to logistical constraints. Therefore, we plan to conduct a covariate 
constrained randomization in 2 blocks following the extension to randomize multiple blocks of 
groups by Carter and Hood.54  In the first block we will have 10 clinics and the second block will 
have 8 clinics if no clinics drop out of block 1 before randomization occurs in the second block.  
The second block will include 2 reserve clinics for use if a clinic should drop out from block 2 
(see Section 8). In the standard covariate constrained randomization all participating clusters 
need to be enrolled before randomization. We are concerned that clinics that would roll out later 
in the schedule may lose interest or drop out if we enroll and randomize all clinics at once at the 
beginning of the study.  An advantage of the blocked compared to the standard randomization is 
that, if a clinic would drop out in the first block before we randomize the second block, we would 

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be able to add clinics in the second block to compensate for the loss.  As we cannot roll out the 
interventions at all clinics at the same time within a block, following randomization, we will then 
randomly pair one ICP clinic and one CCP clinic and then randomly order pairs for intervention 
roll out and recruitment. 
 
As this is a cluster randomized embedded pragmatic trial, patients, intervention delivery 
personnel and recruitment personnel will not be blinded to clinic intervention assignment. 
However, research personnel collecting study surveys by telephone will be blinded.  
9.3  
Definition of Populations 
As this is an embedded pragmatic trial, all adult subjects that present to clinics with LBP and are 
referred to one of the two arms of the trial with initial contact with pain navigator or central 
delivery for data collection will be eligible for the primary analysis as part of the administrative 
sample. A subset of these Veterans will be enrolled as research subjects so that more detailed 
research data can be collected at regular intervals for follow up.  For this subgroup, equivalent 
numbers of Veterans with LBP will be enrolled at each clinic.  
The primary analyses will be conducted on an intention-to-treat basis; patients will be 
analyzed in the group to which they were randomized, regardless of intervention 
adherence, using all available data. The main conclusions drawn from this trial will be based 
on the pre-specified hypotheses outlined below and will be tested with two-sided p-values at the 
standard 0.05 level, except where noted due to multiple primary outcomes.  For all study 
outcomes, we will interpret differences between groups over time with reference to prior 
literature regarding clinically meaningful changes.  Results from exploratory analyses will be 
interpreted with appropriate consideration for their exploratory nature.  Statistical analyses will 
be performed using the latest release of SAS for Windows (Cary, NC) and R software.   
9.4 
Interim Analyses and Stopping Rules 
Interim analyses and stopping rules are not applicable to our embedded pragmatic trial. 
9.5 
Outcomes  
9.5.1 Primary Outcome   
Co-primary outcomes will be pain interference with normal activities and functional status, 
assessed by PROMIS Short Form scores collected in the EHR on the administrative sample 
(n=1680) at baseline and 3 months; 3 months is the primary outcome time point. For baseline 
and 3-month follow-up, we will rely on central delivery personnel and clinical providers in ICP 
and pain navigators in CCP to collect these data in the EHR via progress note templates to 
collect health factors relevant for the analysis for the PROMIS pain interference and functions 
scores (see Section 6).  For the follow-up, a report will be generated every 2-weeks to evaluate 
which participants are due for the 3-month follow-up and the report will be sent to central 
delivery personnel or pain navigator for them to administer these measures (see outcome 
ascertainment study flow diagram in Figure 4.  The window around the 3-month outcome 
assessment will be 1-month. If outcome assessment occurs outside of this defined window they 
will not be included in the primary analysis.  Given that this is an embedded pragmatic trial the 
study team will monitor outcome ascertainment timing at each participating clinical site to 
trouble-shoot any problems or issues to circumvent loss of outcome data. 

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9.5.2 Secondary Outcomes   
Secondary outcomes of PROMIS sleep, opioid use, and utilization will also be obtained 
administratively on the full administrative sample (n=1680). As previously describe for the 
primary measure PROMIS sleep will be collected at the same times as the primary outcomes in 
the EHR (see Section 6). Opioid use will be defined at baseline and then at 12 months later 
using the PMC3 provided definition. For imaging and ED utilization, we will measure use for the 
12 months following referral.   
9.6 
Data Analyses  
Aim 1 Analyses 
The primary outcomes are continuous and will be ascertained at the planned baseline and 
follow-up assessment (3 months) from administrative data collected from the EHR on all 
eligible LBP Veterans presenting at participating clinics. Changes in pain interference 
and/or physical function scores will be estimated and the primary hypotheses tested via 
hierarchical linear mixed-effects models with patients nested within clinics and baseline 
and 3 month values in the response vector.55 Hierarchical linear models are a flexible and 
powerful analytic tool for clustered longitudinal continuous outcomes. The fixed-effect 
portion of the model will have the form: Yijk = β0 + β1*(followup) + β2*(followup*intervention) for 
clinic i, patient j, at time k. Random effects (clinics and time by clinics) will be included in the 
model to account for clustering of patients within clinics as the clinics are the unit of 
randomization, random effects will also be included to account for the within-patient 
correlation between repeated measures over time. We will assess the best fitting random 
effects structure by fitting a variety of random coefficient models (e.g., random intercept 
only, random intercept and linear slope) and assess using Akaike Information Criteria 
(AIC) model selection criteria.56,57 The predictors in the model will include a time effect and 
indicator variables for treatment interacting with the time effect. The intraclass correlation 
capturing the relationship of outcomes between patients seen at the same clinic is 
accounted for via the random effects for the clinics and time by clinics, which are assumed 
to be normally distributed. The model will be fit in the SAS procedure PROC MIXED using 
full likelihood approximation and the hypotheses will be tested by whether the estimated 
coefficient β2 is positive and significantly different than 0 at the 0.025 level due to 2 
primary outcome variables. We will include covariates used in the covariate constrained 
randomization4 (5 potential variables; average pain scores, clinic location (main medical 
center/community clinic), number of participating primary care providers, average level of opioid 
exposure of LBP patients at clinic, and average age of LBP patients at clinic) in our primary 
model as well as a limited number of patient-level covariates that are readily available in 
the EHR (age, gender, race and a comorbidity measure). While we have procedures in 
place to monitor timing of the 3-month follow-up assessment in the EHR, if we have a 
significant number of assessments outside the 1-month window for the 3-month 
assessment that are dropped from the primary analysis, we will conduct a sensitivity 
analysis including the assessments outside the window and estimating a 3-month 
treatment effect from this model. 
 
Secondary Analyses 
We will assess differences in proportions of “responders” between treatment arms for each 
of the primary outcomes.  A “responder” will be defined as achieving 30% improvement in 
pain interference or function scores at 3 months follow up.58 Responder status for those 
missing outcome data will be estimated using best linear unbiased predictors from the 
hierarchical linear model 59so that those missing observed follow up data will be included. 

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We will use a generalized linear mixed model with a logit link function to compare 
differences in responder status between arms where the main predictor of interest will be 
treatment arm adjusting for clustering of VA clinic either with random effects or by 
conditioning.55,60,61 As a sensitivity analysis to explore responder cut points of pain 
interference and function measures, we will compute cumulative proportion responder 
analysis graphs.62  
Secondary outcomes of sleep, opioid use, and health utilization (including chronic 
opioid usage) will also be obtained administratively on all eligible subjects.  The sleep 
PROMIS measure is a continuous outcome that will be assessed at baseline and 3 months 
and similar modeling procedures as described for the primary outcomes will be used.  
Opioid use will be examined in two ways, one as a binary variable based on whether a 
chronic opioid user or not at baseline and 12 months and second using a continuous 
measure of morphine equivalents for opioid dose at baseline and 12 months.63 For the 
dichotomous outcomes, we will use a generalized linear mixed model with a logit link 
function where the main predictor of interest will be treatment arm and will include 
baseline opioid use status (chronic or not chronic) adjusting for clustering of VA clinic 
either with random effects or by conditioning.55,60,61 For opioid morphine equivalent dose, 
we will fit a similar model as was described for the primary outcomes except the follow up 
time point in the model will be for 12 months.  For imaging and ED utilization, we will 
assume a count-like distribution for the number of ED visits in the 12 months of follow up 
and will use generalized linear mixed model for count variables.55  
The survey outcomes for the enrolled subset of patients will be collected at baseline, 3, 
6, 9, and 12 months and will include pain interference, function, intensity, catastrophizing, 
sleep, and depression (see Section 10 for full descriptions).  These are all longitudinal 
continuous outcomes and a hierarchical linear model similar to that described for the 
primary aim will be fit. We will fit random coefficient models as described above (e.g. 
random intercept only, random intercept and linear slope) and assess using AIC model 
selection criteria to determine best model for the covariance structure. Similarly, we will 
determine the best model for the mean structure (e.g. linear, quadratic, dummy coding) as 
there are five outcome measurement occasions guided by descriptive plots and model fit 
assessed using AIC model selection criteria. Due to the timing of administration of 
baseline surveys that some baseline surveys may occur after the initial intervention 
contact, we will conduct sensitivity analysis treating baseline surveys after initial provider 
contact as occurring in the post-treatment period. 
 
Aim 2 Analyses 
As highlighted in the UG3 section we have strong clinical and scientific rationale to 
investigate chronic vs. acute LBP and previous opioid use vs. opioid naïve as a priori 
subgroups for treatment moderation.38 We will define “chronic low back” as pain that has 
persisted for at least 3 months and resulted in pain on at least half the days in the past six 
months to be consistent with the NIH task force definition.49  All participants will have chronicity 
of back pain assessed via the EHR template (see Section 6) at the time of initial referral to a 
given care pathway using questions specified in the NIH minimum dataset.49 Opioid exposure 
prior to pathway entry will be defined as being prescribed at least one prescription opioid for 20 
or more consecutive days (yes or no within 12 months prior to entering pathway).64 This 
definition could be altered if different ones are suggested for use by the PMC3. These data will 
be obtained through VA’s Pharmacy Benefits Management System. 
For the planned subgroup analyses for key moderators on the primary outcomes of 
pain interference and function will be the same modeling framework as described for AIM 
1 with the addition of the indicator variable(s) for the moderator and associated 
interactions.65 The fixed-effect portion of the model will have the form: Yijk = β0 + 

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29 MAR 2012 
β1*(moderator) + β2*(moderator*intervention)+ β3*(followup) + β4*(followup*intervention) 
+β5*(moderator*followup) +β6*(moderator*intervention*followup)  for clinic i, patient j, at time k. A 
random effects (clinics and time by clinics) will be included in the model to account for 
clustering of patients within clinics, as the clinics are the unit of randomization. Differential 
change in pain interference or function by moderator for the two intervention groups is 
supported if the coefficient for β6 is significantly different than zero at the p=0.025 level. 
For the adherence multinomial outcome, we will fit a generalized linear model with a 
random effect for clinic and cumulative logit link function.  As the adherence outcome is 
potentially a 3-level outcome there will be two interaction terms to examine for moderation 
effects (e.g. whether the effect of the intervention by chronicity is different for those 
moderately adherent vs. not adherent and/or those fully adherent vs. not adherent).   
 
Exploratory analyses to identify multidimensional subgroups from combinations of baseline 
characteristics (e.g. age, sex, opioid use) for treatment moderation of the primary outcomes of 
pain and function as well as per protocol adherence to treatment. 
 
Patients are likely to vary in treatment response.  This variation is known as heterogeneity of 
treatment effects (HTE).  Exploration of HTE has typically focused on one-factor-at-a-time post-
hoc subgroup analyses (as described in our planned subgroup analysis); however, it is possible 
to instead identify multidimensional subgroups exhibiting HTE.  In particular, we will apply the 
data-driven method GUIDE66(Generalized, Unbiased, Interaction Detection and Estimation) that 
can be used for longitudinal outcomes, so can incorporate all follow-up outcomes at 3 and 12-
months, as well as multi-response outcomes.  GUIDE uses a regression tree algorithm that 
identifies subgroups with heterogeneous effects and estimates how the treatment effect varies 
across the subgroups. We will include baseline demographic (e.g. age, sex, race) and clinical 
characteristics (e.g. LBP chronicity, opioid use, comorbid conditions) that are available from 
EHR.  GUIDE provides bootstrap confidence intervals for the treatment effects of identified 
nodes and is available via a software package.   
 
We will also examine “adherence” among all patients referred to one of the clinical pathways. 
We define “adherence” according to participant participation in planned sessions with 
intervention team personnel (telephone or in-person) in each care pathway. The number of 
planned sessions will vary between and within arms (e.g. depending on response to 1st service 
in pain navigator arm and depending on risk stratification in integrated pathway arm); therefore, 
we will define adherence as follows: 1) non-adherent – attended no planned sessions 2) 
partially adherent – attended some, but not all planned sessions 3) attended all planned 
sessions. Depending on the number of planned sessions in each pathway we will explore 
additional multi-level variables that may be more informative; structure of the adherence 
variable for Aim 2 analyses will depend on data distribution.  
 
We will describe adherence in both care pathways in order to identify patient characteristics 
potentially associated with program participation and improved pain outcomes. We will not test 
for differences in adherence rates between pathways as our goal is to gain insight into where to 
target clinical programs and focus efforts to improve access to and patient engagement with 
non-pharmacologic pain services.  We will also conduct exploratory analyses on alternative 
definitions of adherence or aspects of intervention receipt.  For example, in the pain navigator 
arm, differentiating based on whether someone actually received one of the recommended 
services.   
 
Exploratory analyses to identify qualitative interactions that define groups of Veterans that have 
greater improvement in pain and function with the integrated care pathway versus the care 

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management program, or greater improvement with care management versus integrated care, 
or no difference in response 
 
As part of personalized medicine, tailored treatment recommendations are the goal.  In this trial, 
we are offering two different treatments, and we want to explore identifying qualitative 
interactions that define groups of individuals that have greater improvement with one treatment 
over the other.  We will apply the tree-based method called Qualitative Interaction Trees 
(QUINT) to identify these subgroups.67,68 QUINT is a tree-based clustering method for data 
obtained from a two-armed trial that identifies three subgroups defined by different baseline 
characteristics of subjects in the study. QUINT uses a partitioning criterion that is maximized 
using a sequential partitioning algorithm or a stepwise binary splitting procedure.  We will use 
the R package quint and apply to our study data to identify characteristics for Veterans where 
integrated care pathway treatment results in greater improvement in outcomes than care 
management pathway, subgroup of Veterans that care management pathway results in greater 
improvements than integrated care pathway and the subgroup for which improvement does not 
differ between treatments. We will first construct a summary of each patient’s repeated 
measures profile to characterize the patient’s change over time at the primary time point 3-
months (i.e., whether or not the patient improved and mean improvement).  Empirical Bayes 
estimates from hierarchical linear models will be used to generate individual-level estimates of 
mean improvement for each of the primary outcomes. Currently this software only supports 
continuous outcomes so we would not be able to apply to the multilevel response adherence 
outcome; however, we will monitor updates for expansion to other distributions of outcomes. 
Limitation of this methods are that subjects with missing data on any included variables are 
omitted from the analysis, the effect of clustering within clinics is not addressed, and categorical 
baseline characteristics of more than two categories cannot be used. 
 
Statistical methods for heterogeneity of treatment effects (HTE) are a rapidly developing field.  
We will monitor the development of new methods that may be applicable to our study for 
adapting the analysis plan for this aim, and work closely with the PMC3 Biostatistics Working 
Group and Dr. Lisa Wruck (an internal advisory member for this proposal) to ensure robustness 
of our chosen methods. 
 
Missing Data. We do not anticipate much missing data in the main predictors of interest, 
intervention arm and patient characteristics available in the EHR or assessed at baseline 
in survey outcomes.  There may be missing values in the outcome measures due to 
dropout, death, a missed interim assessment or assessment outside 1-month window for 
3-month follow-up, or item non-response.  However, hierarchical linear mixed models via 
maximum likelihood estimation, our main analysis technique for the primary outcomes, 
implicitly accommodate missingness at random (MAR). 55Therefore, inferences will be 
valid even with differential dropout by intervention arm. We will thoroughly explore reasons 
for dropout, and depending upon the type and scope of missing data, we may explore the 
sensitivity of intervention effects to different missing data mechanisms (MAR vs. MNAR).69 
Our plan would be to conduct sensitivity analyses to evaluate the sensitivity of the 
assumption of MAR and/or MNAR on intervention effects. If our primary model included 
design variables only (treatment, stratification variables, clinic) this model would meet the 
MAR assumptions if missing data is related to previous outcome assessments or design 
variables included in the primary model. We can assess the sensitivity of the MAR 
assumption by conducting an analysis that includes auxiliary variables (either as additional 
variables in primary models or by conducting a multiple imputation including auxiliary 
variables).  These auxiliary variables or other baseline characteristics for the large sample 
may be limited due to availability in the EHR. We are currently proposing to include age, 

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sex, race, and a comorbidity index in our primary analysis that may strengthen our MAR 
assumption. To explore the MAR assumption, outcomes will be multiply imputed using 
principled methods in SAS (via PROC MI or IVEware).70  Multiple imputation provides a 
framework for being able to incorporate information from important auxiliary variables while still 
preserving a parsimonious main treatment effect model and is described as a significant 
advantage in recommendations from Panel on Handling Missing Data in Clinical Trials.71 Note 
that if needed, we will utilize imputation methods that account for the multiple levels of 
correlation inherent in the clustered data structure.  If we cannot justify the assumption of 
MAR, we will explore the sensitivity of intervention effects to the MNAR assumption; we 
will follow guidelines in Mallinckrodt72 and Ratitch et al69 for model selection and pattern 
mixture modeling.   
10. MEASURES AND DATA COLLECTION  
Outcome measures and timing of collection is summarized in Table 10.  The data collection 
process is explained in subsequent sections.   
 
 
Table 10. Summary of Measures.     
Outcome 
Variable 
Definition 
Data Source 
Baseline 
3 months 
6 months 
9 months 
12 months 
Pain  and Pain Impact Measures 
Pain Interference 
PROMIS SF- 4 item 
CDW health factor 
data element 
x 
x 
 
 
 
PROMIS SF- 4 items 
Patient report on CATI 
survey 
x 
x 
x 
x 
X 
Physical function 
PROMIS SF- 4 item 
CDW health factor 
data element 
x 
x 
 
 
 
PROMIS SF-4 items  
Patient report on CATI 
survey 
x 
x 
x 
x 
X 
Pain intensity 
Numeric Scale (0-10)  
CDW health factor 
data element 
X 
X 
 
 
 
Pain intensity  
PEG Pain Screening Tool 
Patient report on CATI 
survey 
x 
x 
x 
x 
X 
Catastrophizing 
NIH recommended minimum 
dataset (2 items)  
Patient report on CATI 
survey 
x 
X 
x 
X 
X 
Self-Efficacy 
Patient Self Efficacy 
Questionnaire (2 items)  
Patient report on CATI 
survey  
x 
X 
x 
X 
X 
Opioid exposure 
NIH recommended minimum 
dataset - 1 item  
Patient report on CATI 
survey 
x 
 
x 
 
X 
At least one prescription opioid 
for 20 or more consecutive days 
Pharmacy Benefits 
Management 
 
x 
 
 
 
X 
Quality of life 
Euroquol - 5 items  
Patient report on CATI 
survey 
X 
x 
 
 
X 
Adverse clinical 
outcomes 
(1) accidents resulting in wounds 
or injuries, (2) opioid-related 
accidents and overdose, (3) 
alcohol- and nonopioid drug–
related accidents and overdose, 
(4) self-inflicted injuries and (5) 
violence-related injuries  
CDW inpatient & 
outpatient  
Non-VA care (Fee) 
inpatient & outpatient 
(ICD codes) 
 
 
 
 
X 
Co-Morbidity Measures 
Sleep 
disturbance 
PROMIS SF- 4 item 
CDW health factor 
data element 
x 
x 
 
 
 

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10.1 Survey Data Collection Process  
Because the participation in the two care pathways described earlier in the protocol is 
considered a quality improvement initiative (see memo in appendix), local site activities 
and participation in the two care pathways will not require IRB oversight. Two separate 
(Durham VA and Duke University) IRBs have been approved for described research 
related project activities.  The Durham VAMC IRB will be the IRB of record to cover 
participant survey recruitment activities, including obtaining verbal informed consent for 
participating in the telephone survey, administering a telephone survey for baseline data 
collection activities, medical record chart abstraction, and post data collection analysis 
activities. The Duke University IRB will cover follow up data collection activities 
performed by the Duke Clinical Research Institute Call Center.  
As described earlier in Section 4, centrally located Durham VA study staff will generate 
an opt-out letter signed by the research team that will be mailed to all potentially eligible 
patients enrolled in participating VA primary care clinics and a query will be run biweekly 
by the Durham VA study staff team to identify eligible patients based on inclusion and 
exclusion criteria.  Patients who have not opted-out will be contacted by Durham VA 
study staff to consent and collect baseline data and verbally consent to be interviewed 
every three months by the Duke Clinical Research Institute call center staff.  The table 
above documents the potential questions which will be asked in follow up interviews.  
These questions will serve as the CRFs for the follow up data collection activities.  
Pre-consent screening data will be collected in the VA instance of REDCap survey 
software.  Following verbal consent, baseline assessments will also be collected by VA 
staff using the VA instance of REDCap.  Post-consent, follow-up assessments will be 
conducted by the DCRI Call Center.  Follow-up survey data will be collected and stored 
PROMIS SF - 4 item 
Patient report on CATI 
survey 
x 
x 
x 
x 
X 
Sedative/hypnotic 
exposure 
At least one prescription 
sedative/hypnotic for 20 or more 
consecutive days 
Pharmacy Benefits 
Management 
 
x 
 
 
 
X 
PTSD symptoms 
PCL-5 
CDW health factor 
data element 
x 
 
X 
 
X 
Depressed Mood  
PHQ-2 Questionnaire 
Patient report on CATI 
survey 
x 
 
x 
 
X 
Alcohol  
AUDIT-C 
Patient report on CATI 
survey 
x 
 
 
 
 
Utilization Measures 
Imaging, 
Providers, and 
Procedures  
 
Utilization  
- 
Radiographs, MRI, CT 
- 
Provider types and 
number  
- 
Injection, ablation, and 
surgery  
CDW inpatient & 
outpatient  
Non-VA care (Fee) 
CPT outpatient + ICD 
codes 
 
 
 
 
x 
ED visits 
ED visits 
- 
VA 
- 
Non-VA 
CDW inpatient & 
outpatient  
Non-VA care (Fee) 
inpatient & outpatient  
 
 
 
 
X 
Pain-related ED 
visits 
ED visits 
- 
VA 
- 
Non-VA 
CDW inpatient & 
outpatient files; 
Non-VA care (Fee) 
inpatient & 
outpatient  + ICD 
codes 
 
 
 
 
X 

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in a secure Microsoft Access database at Duke.  The recruitment and participant 
management system will be a Durham VA in-house application named Study Tracking 
that will be run by the VA staff.  It will provide all functionality needed to keep track of 
study participants as they move through the protocol.  Study Tracking will interface with 
the Microsoft Access database.  Following consent, participant contact information will 
be duplicated from Study Tracking into the designated MS Access database at Duke.  
DCRI’s Call Center software will interact with the MS Access database to create a call 
schedule.  When someone is due for a follow-up call, a member of the Call Center will 
be prompted to contact the participant and the follow-up survey results will be stored in 
MS Access. Figure 5 provides a general overview of the data flow for the project across 
the two participating entities. 
    
 
 
 
 
 
 
 
 
 
 
 
10.2 Data Management  
The Durham VA and Duke Clinical Research Outcomes Operations group will serve as the 
coordinating center and data management center for this study.  The Durham VA will be 
responsible for enrollment, consenting participants for the follow up telephone survey 
assessments, baseline data collection, as well as data analysis after the database lock.  The 
DCRI call center will be responsible for administering follow up surveys. Other than standard 
demographic information, all of the outcome measures being collected for this study via follow 
up surveys are listed in the appendix and are harmonious with other existing patient reported 
pain and pain impact measures collected within the field.  
The follow up surveys will be administered at three, six, nine, and twelve months post baseline, 
and participants will be paid $25 for completing each survey, including baseline. Payments will 
be made via online gift card or mailed to the participants’ address. Payments will be 
administered through the Duke Clinical Research Institute Call Center. 
Figure 5- General Data Flow Overview for AIM-Back 
 

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10.3 Quality Assurance  
All employees (DCRI and VA) will receive the appropriate training to use the various systems.  
VA employees are already familiar with using Study Tracking, MS Access, and REDCap.  DCRI 
call center members are familiar with the call center software and MS Access.  A few 
designated employees will be trained on ensuring and verifying data is moved from the VA to 
Duke and back on a scheduled basis so that data flows back and forth in an appropriate manor. 
All new interviewers complete a required intense 4-6-week program that covers topics on 
Human Subject Protection (HSP), HIPAA Privacy and Security, standardized interviewing 
procedures, and instrument specific training. Interviewers follow the questionnaire scripts which 
are displayed directly on their computer screen as they precede through the interview.  
 
The standard interviewing training module teaches and guides interviewers to remain neutral, to 
read questions clearly and slowly, and to avoid rewording, asking supplemental questions, 
making assumptions, or acting surprised/interested to a subject’s responses. Until training is 
fully complete, interviewers complete any questionnaires under supervision. 
 
In addition to the thorough training, project staff monitor and perform quality assurance checks 
on interviewers on an ongoing basis. Using a checklist, staff monitor and provide feedback to 
interviewers about any issues during an interview. Study staff also review data from completed 
interviews and data discrepancy checks to ensure questionnaires are completed thoroughly, no 
questions are being systematically skipped and that valid responses are being captured and to 
notice any trends in data quality that may indicate any biases from the way surveys are 
administered.  We will not be looking for trends in the data over time, but instead determining if 
we can improve on any missing data trends, or invalid response patterns noticed during data 
quality checks. If any issues arise during the monitoring or during any quality assurance checks, 
interviewers are provided with a re-training and receive continual monitoring. 
 
10.3.2 Quality Control Committee  
Not applicable for this embedded pragmatic trial.   
10.3.3 Metrics 
The MS Access and Study Tracking databases will be used to track rates of follow up 
completion in real time. If at any time follow up completion rates are concerning, study staff 
members will evaluate processes and brainstorm better ways to capture follow up data.  The 
Duke Clinical Research Institute Call Center staff have extensive experience collecting follow up 
information and a strong track record of high completion rates. Based on past experiences, we 
anticipate between a 75-90% success rate for collecting follow up data.  On average, it takes 
around six attempts to make contact and successfully collect data via the DCRI Call Center.  In 
order to achieve a high success rate, the interviewing staff will continue to contact participants 
as many times as possible during the eligibility window (14 days prior to an interval date, and 45 
days post an interval date).   
10.3.4 Protocol Deviations 
Because the participation in and data collected from the two care pathways described earlier in 
the protocol is considered a quality improvement initiative (see memo in appendix), there will be 
no increased risk from standard of care for participants during these project activities.  For the 
sub-group of participants who will be consented to be contacted for the follow-up telephone 
survey-based assessments, we expect these activities to be considered minimal risk from the 

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Duke University Health System IRB. The loss of confidentiality will be the greatest risk for 
participating in the telephone survey-based assessments. There is no investigational drug or 
device, and all data collected through EMR records are considered standard of care data. One 
reportable protocol deviation we anticipate would be enrolling participants who do not meet our 
established eligibility criteria outlined in section four. Another potential protocol deviation would 
be collecting data outside of the established time windows for the follow up subgroup.  For the 
three, six, nine, and twelve-month telephone surveys, we will begin attempting data collection 
two weeks before the interval and end attempts for data collection 45 days after the interval 
date.     
10.3.5 Monitoring 
Site monitoring (e.g. recruitment and adherence) described earlier (Section 8). 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
All baseline and follow up research material will be obtained from participants during phone calls 
with Durham VA and Duke Clinical Research Institute Call Center study staff or from the 
medical files of participating Veterans by Durham VA research staff. Data obtained from medical 
files will be drawn from existing records generated in the course of clinical care. The following 
human subjects related data elements will be collected for this study, with the source(s) of 
information noted: 
• 
Presence of inclusion and exclusionary health conditions and clinical criteria (VA 
electronic medical records and self-report) 
• 
Subject demographic and clinical characteristics, including age, gender, race / ethnicity, 
income, education level, and marital status (VA electronic medical records and subject 
self-report) 
• 
Subject-reported clinical and functional status, health information quality of life, pain 
impact measures, information on co-morbidities (scales administered by research staff) 
• 
Completion of telephone calls as part of the study 
• 
Participant health care use during the study period (VA electronic medical records) 
Only individuals officially assigned to the study team will have access to individually identifiable 
information about human subjects. This will include the principal investigators, co-investigators, 
statisticians, computer programmer, project coordinator, and research assistants.  All of these 
individuals will have completed required human subjects training and will be included on a staff 
listing with the IRB.   
Potential Risks. There are few potential risks associated with this study. It is possible that some 
participants may feel uncomfortable answering some of these questions.  We will only ask 
questions that involve data that are important for study outcomes, and we will inform 
participants that they may refuse to answer any questions, but still be involved in the study.  
Since personal data will be collected as part of this study, there is a risk of loss of confidentiality.  
However, we will take several measures to minimize this risk.  First, we will only collect the data 
necessary for the study.  Second, all electronic data will be stored on secure servers, rather 
than on individual desktop or laptop computers.  Third, electronic study data will be kept in 
folders and databases that are only accessible to key personnel who are IRB-certified and 
whose job functions require access to these data.   
Adequacy of Protection from Risks; including recruitment and informed consent and 
protections against risks including data security and sharing  

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Protection against risk. We do not anticipate any significant physical, psychological, social, 
financial, or legal risks to be associated with participation in this study. In order to minimize any 
risks regarding privacy of individuals and confidentiality of data, we will take specific measures 
to protect both paper and electronic data.  Except when required by law, participants will not be 
identified by name, social security number, address, telephone number, or any other direct 
personal identifier in study records disclosed.  All electronic data will be stored on secure 
servers in folders and databases accessible only to study personnel whose job functions require 
access to this information.  We will minimize the use of paper data collection by entering 
information from telephone screening interviews, baseline and follow-up assessments, and 
intervention tracking directly into a computer database.  Any paper-based documents will be 
stored in a locked filing cabinet in a locked office.  We have used these data security 
procedures successfully in multiple prior studies.  We will follow standard procedures for 
reporting any adverse events and other unanticipated problems to the IRB.  Scopes of practice 
for all research staff members will be approved by and maintained on record with the Durham 
and Duke IRBs.  
11.1 Institutional Review Board (IRB) Review  
IRB protocol review in progress at Duke University and Durham VA. 
11.2 Informed Consent Forms 
A script for the approved informed consent documents for the Durham VA IRB’ is included as 
Appendix X. The Durham VA informed consent gives Duke University permission to contact 
participants through the call center.  Trained research staff will obtain informed consent 
according to existing VA or Duke policies and procedures using an IRB approved protocol. 
Because the study is conducted entirely over the phone, we were granted a waiver of 
documentation of informed consent and HIPAA authorization. We will maintain study files with 
documentation of the conversation in which verbal consents and authorizations were obtained, 
for inspection by regulatory bodies as appropriate. 
 
After obtaining verbal informed consent, the VA RA will collect baseline survey data from all 
study participants. A well established and IRB-approved protocol will be used for Veteran who 
express suicide ideation during baseline or at any of the follow-up phone calls. The study will be 
conducted according to Good Clinical Practice guidelines, the U.S. Code of Federal Regulations 
(CFR) Title 21 CFR (Part 50 – Protection of Human Subjects and Part 56 – Institutional Review 
Boards) and the Declaration of Helsinki.  
11.3 Participant Confidentiality  
The Durham HSR&D COIN adheres to VA policy and Durham VAMC IRB requirements, and 
has also developed additional Standard Operating Procedures for data security which have 
been designed to ensure continued confidentiality, integrity, and availability of research data. 
These procedures, which protect both paper and computer based records, have been used 
successfully in many studies, and will be followed for the proposed study.  
With respect to all data, these procedures mandate the following to ensure confidentiality and 
safe handling of all data:  
1. Access to all participant data and information will be restricted to authorized personnel.  
2. Participants will not be identified by name in any reports or publications, nor will data be 
presented in such a way that the identity of individual participants can be inferred.  

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3. Each participant will be assigned an anonymous study ID which will be used on all study 
forms.  
4. All study personnel will maintain certification with the Durham VAMC IRB that they have 
completed training in research ethics and confidentiality.  
With respect to paper based records, these procedures mandate the following:  
1. All study records that contain participant information will be kept in secured, locked areas 
when not in use.  
2. In addition, such materials, when in use, will be kept safe from public scrutiny.  
With respect to computer based records, the following practices are followed:  
1. All research data are stored on approved servers which are in a physically secured server 
room.  
2. Individual computer accounts, password protected, are issued to staff members.  
3. Access to computer data is granted by OI&T personnel after confirming appropriate 
documentation through the IRB, per COIN policies.  
Utilization data, in particular, will be downloaded directly from national files to the Durham 
HSR&D COIN servers. Of study personnel, only the Statisticians will have access to these data, 
which will not be moved from this secured environment.  
This proposal represents a collaboration between the Durham VA and Duke University. Consent 
and HIPAA authorization procedures will include provisions for participants to grant permission 
for study data, including personal health information (PHI), to be stored on Duke University 
servers. 
All patient information collected in the context of this research study, and even the fact that an 
individual is participating in the study, will be considered confidential. This confidentiality will be 
assured through several mechanisms. First, each participant will be assigned an anonymous 
study ID which will be used on all study forms. Second, all study forms and paper records that 
contain participant information will be kept in secured, locked areas when not in use. In addition, 
such materials, when in use, will be kept away from public scrutiny. Materials that need to be 
discarded will be destroyed. Third, access to all participant data and information will be 
restricted to authorized personnel. In the case of computerized study data, access to data will 
be password protected and staff members will be assigned individualized passwords that allow 
them access to only those elements of the data management system to which they are 
authorized. In addition, all study personnel will maintain certification with the Duke and Durham 
VA IRB that they have completed training in research ethics, which includes training on 
confidentiality. Finally, participants will not be identified by name in any reports or publications, 
nor will data be presented in such a way that the identity of individual participants can be 
inferred.  
11.4 Study Discontinuation  
This study may be discontinued at any time by the DSMB, IRB, the NCCIH, the OHRP, the 
FDA, or other government agencies as part of their duties to ensure that research participants 
are protected. The NCCIH must be notified of any IRB or agency discussions that may result 
temporary or permanent study discontinuation.  There is more detailed information on study 
discontinuation in the DSMP (see Appendix X).  
12. COMMITTEES 
Internal Scientific Advisory Panel 
The PIs will be supported in their leadership role by an Internal Scientific Advisory Panel, which 
includes expertise and connections to institutional infrastructure to support the needs of the 

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study over the course of award, maximize the study’s impact, and ensure our objective is 
achieved. The ISAP will meet quarterly in person and/or via teleconference to review overall 
progress and timelines, ensure integration of resources and infrastructure, and to prioritize 
activities moving forward. When applicable for study planning or data interpretation, the PIs will 
invite advisors to join team meetings and will be available to consult on issues via email or 
telephone on an ad hoc basis.  
 
Study PIs participate in the monthly PMC Steering Committee meeting and we have an active 
representative on all PMC workgroups, which also meets monthly.  Finally, we have study 
specific meetings once per month for the entire team (i.e. “Large Group Meeting”, monthly 
cadence), and we have task specific meetings as needed for work directed at milestones and 
deadlines (i.e. “Task Group Meetings”, weekly cadence).  The NIH representative is included in 
all invitations for the Large Group Meetings and can join via teleconference.  
13. PUBLICATION OF RESEARCH FINDINGS  
One advantage of this embedded pragmatic trial is that the care strategies were meant to be 
sustainable which will improve translation into routine clinical practice outside of the sites that 
participated in the trial, if results warrant such translation.  The results of this study will be 
relevant to broad audiences, thus we plan to disseminate study results in both academic and 
non-academic forums. Our dissemination efforts will be assisted by the Durham HSR&D COIN 
Stakeholder Engagement Core, a group formed to help investigators identify important 
stakeholders with whom to share research results, including government/policy makers, 
patients, Veterans, the public, researchers, advocacy groups, and the press.  Examples of how 
dissemination and implementation of trial findings will proceed:   
• 
Preliminary findings and results will be presented to the NIH Pain Management 
Collaboratory Work Group This input will help to guide future implementation strategies 
within the VA Health System and beyond  
• 
Prior to dissemination in publication or presentations, Veteran and provider stakeholders will 
be presented with the data and asked to provide input regarding their own interpretations of 
research findings, particularly the relevance to the stakeholder category to which they 
belong. 
• 
Provider stakeholders involved with this proposal will facilitate dissemination by presenting 
key findings at meetings and conferences.   
• 
Scientific dissemination will be aimed at those most likely to have a vested interest in 
implementing these trial findings.  
• 
At conclusion of study Duke, VA, and clinicaltrials.gov websites will host summary data, 
downloadable versions of key papers, and the manual of procedures and operations for 
each care pathway.   
 
 

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15. SUPPLEMENTS/APPENDICES 
See Accompanying PDF with Appendices I - XI