Group-based Mindfulness for Patients With Chronic Low Back Pain in the Primary Care Setting
Phase: NA
Conditions: Chronic Pain, Back Pain
Sponsor: Boston Medical Center

 
Study Product Guidelines and Considerations 
1 of 57 
Version 1.1 
 
 
1 June 2018 
 
OPTIMUM: Optimizing Pain Treatment In Medical settings Using 
Mindfulness  
 
 
Principal Investigator:   
Natalia E. Morone, MD, MS  
Associate Professor of Medicine 
Boston Medical Center/ Boston University 
 
NCT04129450 
 
Statistical Analysis Plan- pages 28-33 
 
 
Supported by:  
The National Center for Complementary and Integrative Health  
UH3AT010621 
 
 
 
 
 
 
 

 
Study Product Guidelines and Considerations 
2 of 57 
Version 1.1 
 
 
13 November 2020 
 
Tool Revision History 
Version 
Number 
Version Date 
Summary of Revisions Made 
Consent change 
Yes/No 
1 
9/17/20 
Original NCCIH Approval of UH3 Protocol 
Yes 
1.1 
11/13/20  
Updated to reflect virtual delivery of 
intervention.  
Yes 
1.2 
11/17/21 
Updated to reflect new exclusion criteria 
• First degree relatives (parents, 
siblings, child) of someone who has 
participated or is participating in the 
OPTIMUM study 
• Members of the same household  
• Not a patient at a participating 
clinic or persons not planning to 
continue as a patient at a 
participating clinic for 12 or more 
months 
 
Yes 
1.3 
3/1/22 
1. Added UNC Healthcare to 
recruitment sites 
2. Added a new definition of AEs 
3. Added - Refer to the “Adverse 
Event workflow” sheet for 
information on how and when to 
report AEs/SAEs or Unanticipated 
problems - to section 7.4 
“Reporting procedures”  
No 
1.4 
10/06/22 
• Dr. Tuhina Neogi has been removed 
as a co-Investigator. 
• Subjects in the control group will be 
offered the OPTIMUM intervention 
after their participation in the study 
is complete. 
• Added the word “approximately” to 
the following sentence:  Group size 
will be approximately 5-12 patients 
No 

 
Study Product Guidelines and Considerations 
3 of 57 
Version 1.1 
 
 
13 November 2020 
per session. (page 18: Frequency, 
setting and providers) 
 
1.5 
 
Research Activities now includes new 
measures: trauma scale and global 
mindfulness, to be collected once at any 
time point during study participation. 
No 
(a consent 
addendum was 
created) 
  

 
Study Product Guidelines and Considerations 
4 of 57 
Version 1.1 
 
 
13 November 2020 
TABLE OF CONTENTS 
Page No. 
FULL PROTOCOL TITLE …………………………………………………………………….1 
    Tool Revision History ………………………………………………………………………………...2 
TABLE OF CONTENTS ……………………………………………………………………….3 
    STUDY TEAM ROSTER ……………………………………………………………………6 
    PARTICIPATING STUDY SITES ………………………………………………………….6 
    SYNOPSIS …………………………………………………………………………………...10 
1. STUDY OBJECTIVES ……………………………………………………………………11 
1.1. Primary Objectives ………………………………………………………………………………11 
1.2. Secondary Objectives ……………………………………………………………………………11 
2. BACKGROUND AND RATIONALE ……………………………………………………11 
2.1. Background on Condition ……………………………………………………………………….11 
2.2. Study Rationale ………………………………………………………………………………….13 
3. STUDY DESIGN …………………………………………………………………………...14 
4. SELECTION AND ENROLLMENT OF PARTICIPANTS ……………………………14 
4.1. Inclusion Criteria ………………………………………………………………………………..15 
4.2. Exclusion Criteria ……………………………………………………………………………….15 
4.3. Study Enrollment Procedures …………………………………………………………………...15 
5. STUDY INTERVENTIONS ………………………………………………………………16 
5.1. Interventions, Administration and Duration …………………………………………………….16 
5.2. Handling of Study Interventions ………………………………………………………………..17 
5.3. Concomitant Interventions ………………………………………………………………………18 
5.3.1. Allowed Interventions …………………………………………………………………..18 
5.3.2. Required Interventions ………………………………………………………………….18 
5.3.3. Prohibited Interventions …………………………………………………………………18 
5.4. Assessment of Adherence ……………………………………………………………………….18 
6. STUDY PROCEDURES …………………………………………………………………..19 
6.1. Schedule of Evaluations …………………………………………………………………………19 
6.2. Description of Evaluations ………………………………………………………………………19 
6.2.1. Screening Evaluation ……………………………………………………………………19 
6.2.2. Enrollment, Baseline and/or Randomization ……………………………………………20 
6.2.3. Blinding …………………………………………………………………………………23 

 
Study Product Guidelines and Considerations 
5 of 57 
Version 1.1 
 
 
13 November 2020 
6.2.4. Follow up Visits ……………………………………………………………………….23 
6.2.5. Completion/Final Evaluation ………………………………………………………….23 
7. SAFETY ASSESSMENTS ……………………………………………………………….23 
7.1. Specification of Safety Parameters …………………………………………………………….24 
7.2. Methods and Timing for Assessing, Recording, Analyzing Safety Parameters ……………….24 
7.3. Adverse Events and Severe Adverse Events ……………………………………………………24 
7.4. Reporting Procedure ……………………………………………………………………………25 
7.5. Follow up for Adverse Events ………………………………………………………………….25 
7.6. Safety Monitoring ……………………………………………………………………………….25 
8. INTERVENTION DISCONTINUATION ……………………………………………….25 
9. STATISTICAL CONSIDERATIONS ……………………………………………………25 
9.1. General Design Issues …………………………………………………………………………..25 
9.2. Sample Size and Randomization ……………………………………………………………….26 
9.3. Definition of Populations ………………………………………………………………………..26 
9.4. Interim Analyses and Stopping Rules …………………………………………………………..26 
9.5. Outcomes ……………………………………………………………………………………….27 
9.5.1. Primary Outcomes ………………………………………………………………………27 
9.5.2. Secondary Outcomes ……………………………………………………………………27 
9.6. Data Analyses …………………………………………………………………………...27 
10.  DATA COLLECTION AND QUALITY ASSURANCE ……………………………….30 
10.1. 
Data Collection          . . . .………………………………………………………………30 
10.2. 
 Data Management …………………………………………………………………... 30 
10.3. 
 Quality Assurance ………………………………………………………………………32 
10.3.1. Training ………………………………………………………………………………… 32 
10.3.2. Quality Control Committee ……………………………………………………………..32 
10.3.3. Metrics ………………………………………………………………………………….32 
10.3.4. Protocol Deviations ……………………………………………………………………..32 
10.3.5. Monitoring ………………………………………………………………………………33 
11.  PARTICIPANT RIGHTS AND CONFIDENTIALITY ………………………………..33 
11.1. 
 Institutional Review Board (IRB) Review ……………………………………………..33 
11.2. 
 Informed Consent Forms ……………………………………………………………….33 
11.3. 
 Participant Confidentiality ……………………………………………………………..33 
11.4. 
 Study Discontinuation ………………………………………………………………….33 
12.  COMMITTEES …………………………………………………………………………..34 

 
Study Product Guidelines and Considerations 
6 of 57 
Version 1.1 
 
 
13 November 2020 
13.  PUBLICATION OF RESEARCH FINDINGS ………………………………………….34 
14.  REFERENCES …………………………………………………………………………….34 
15.  SUPPLEMENTS/APPENDICES ………………………………………………………...39 
15.1. 
Appendix A (Consent Form Template) …………………………………………39 
15.2. 
Appendix B (Important Medical Event Form) …………………………………46 
15.3. 
Appendix C (Screening Questions) ……………………………………………..47 
15.4. 
Appendix D (Timeline of the Study) ……………………………………………49 
 
 

 
Study Product Guidelines and Considerations 
7 of 57 
Version 1.1 
 
 
13 November 2020 
STUDY TEAM ROSTER  
 
Principal Investigator: 
 
Natalia E. Morone, MD, MS  
Associate Professor of Medicine 
Boston Medical Center/ Boston University 
801 Massachusetts Avenue, 2nd floor 
Crosstown Building 
Boston, MA 02118 
Telephone: 617-414-6652 
Fax: 617-414-4676 
Email: Natalia.morone@bmc.org 
 
 
PARTICIPATING STUDY SITES 
 
1. Boston Medical Center (BMC), Boston, MA  
 
            Site Principal Investigator: 
 
Natalia Morone, MD, MS  
Associate Professor of Medicine 
Boston Medical Center/ Boston University 
Crosstown Building 
801 Massachusetts Avenue, 2nd floor 
Boston, MA 02118 
Telephone: 617-414-6652 
Fax: 617-414-4676 
Email: Natalia.morone@bmc.org 
 
Co-Investigators: 
 
Janice Weinberg, ScD 
Professor of Biostatistics and Director, MS in Clinical Research 
Boston University  
801 Massachusetts Avenue, CT-330 
Boston, MA 02118 
Telephone: 617-358-2452 
Fax: 617-638-6484 
Email: janicew@bu.edu 
 
Karen E. Lasser, MD, MPH 
Professor of Medicine and Public Health 
Boston Medical Center/ Boston University  
            801 Massachusetts Avenue, Crosstown #2094 

 
Study Product Guidelines and Considerations 
8 of 57 
Version 1.1 
 
 
13 November 2020 
Boston, MA 02118 
Telephone: 617-414-6688 
Fax: 617-414-7955 
Email: Karen.lasser@bmc.org 
 
 
2. University of Pittsburgh, Pittsburgh, PA  
 
Site Co-Principal Investigators: 
 
Kathleen McTigue, MD, MPH 
Associate Professor of Medicine 
University of Pittsburgh  
230 McKee Place, Suite 600 
Center for Research on Healthcare 
Pittsburgh, PA 15213 
Telephone: 412-692-2940 
Fax: 412-692-4838 
Email: Kmm34@pitt.edu 
 
Carol M. Greco, PhD 
Associate Professor of Psychiatry 
University of Pittsburgh 
UPMC Center for Integrative Medicine 
580 S. Aiken Avenue, Suite 310 
Pittsburgh, PA 15232 
Telephone: 412-623-6873 
Fax: 412-623-6414 
Email: grecocm@msx.upmc.edu 
 
Co-Investigators: 
 
Holly N. Thomas, MD MS 
Assistant Professor of Medicine and Clinical & Translational Research 
            University of Pittsburgh 
            230 McKee Place Suite 600 
            Pittsburgh, PA 15213 
            Telephone: 412-586-9836 
            Fax: 412-692-4838 
            Email: thomashn@upmc.edu 
 
3. University of North Carolina (UNC) at Chapel Hill in partnership with Piedmont 
Health Services, NC and UNC HealthCare 
 
Site Co-Principal Investigators: 
 

 
Study Product Guidelines and Considerations 
9 of 57 
Version 1.1 
 
 
13 November 2020 
Susan A. Gaylord, PhD 
Associate Professor, Department of Physical Medicine and Rehabilitation  
Director, Program on Integrative Medicine  
UNC School of Medicine/ University of North Carolina at Chapel Hill 
Chapel Hill, NC 27599-7200 
Telephone: 919-966-8586 
Fax: 919-843-5452 
Email: gaylords@med.unc.edu 
 
Kim Faurot, PA, MPH, PhD 
Assistant Professor 
University of North Carolina, Chapel Hill 
Telephone: 919-357-7235 
Email: faurot@med.unc.edu 
 
Co-Investigators: 
 
Maria Gabriela Castro, MD 
Assistant Professor and Assistant Residency Director UNC Family Medicine 
University of North Carolina, Chapel Hill 
590 Manning Dr, CB #7595 
Chapel Hill, NC 27599 
Telephone: 984-974-4888 
Email: Gabriela_Castro@med.unc.edu 
 
 
Research Fellow: 
Isabel Roth, Dr.PH, MS 
Postdoctoral Research Fellow, Department of Physical Medicine and Rehabilitation 
Program on Integrative Medicine  
University of North Carolina, Chapel Hill 
Wing D Room 186 
Chapel Hill, NC 27599 
Telephone: 202-550-7760 
Email: iroth@email.unc.edu 
  
 
4. University of Massachusetts (UMass): 
 
Co-Investigator: 
 
Paula Gardiner, MD, MPH 
Associate Professor, Associate Research Director 
Medical Group Visit Program Director 
Center for Integrated Primary Care 
Department of Family Medicine and Community Health 

 
Study Product Guidelines and Considerations 
10 of 57 
Version 1.1 
 
 
13 November 2020 
UMass Memorial Health Care 
University of Massachusetts 
55 Lake street North 
Worchester, MA 01655-0002 
Telephone: 774-441-6716 
Fax: 774-441-6212 
Email: Paula.gardiner@umassmed.edu 
 
Scientific Officer: 
 
Luke E. Stoeckel, PhD 
Program Director, Mechanistic and Translational Decision Science in Aging Research 
National Institute on Aging 
Division of Behavioral and Social Research 
7201 Wisconsin Avenue, Suite 3S600 
Bethesda, Maryland 20892 
Telephone: 202-570-9388 
Email: luke.stoceckel@nih.gov 
 
Program Officer: 
 
Wendy Weber, ND, PhD, MPH 
Chief, Clinical Research in Complementary and Integrative Health Branch 
Division of Extramural Research 
National Center for Complementary and Integrative Health 
National Institutes of Health 
6707 Democracy of Boulevard, Suite 401 
Bethesda, MD 20892-5475 
Telephone: 301-402-1272 
Fax: 301-480-1587 
Email: weberwj@mail.nih.gov 
 
 
 
 
SYNOPSIS 
Study Title 
OPTIMUM: Optimizing Pain Treatment In Medical settings Using Mindfulness  
Objectives  
The aims of the study are the following: 1) to integrate and test an evidence-based mindfulness 
clinical pain program, OPTIMUM, for patients with cLBP in the primary care setting. 2) To 
evaluate use of healthcare resources by patients as documented in the electronic health record. 3) 

 
Study Product Guidelines and Considerations 
11 of 57 
Version 1.1 
 
 
13 November 2020 
To evaluate PCP and practice site use of, satisfaction with, and integration of OPTIMUM. 
Design and Outcomes 
This is a Pragmatic Clinical Trial (PCT) with a goal of informing clinicians, patients, 
administrators and policy makers how mindfulness can work in a real-life clinical setting, impact 
outcomes, increase access to non-opioid treatments and be reimbursable. It will be conducted 
with four HCS sites (Boston Medical Center, MA, a safety net health system; UPMC, Pittsburgh, 
PA, a large academic health system; Piedmont Health Services, NC, a network of federally 
funded health centers in partnership with the University of North Carolina Chapel Hill (UNC-
CH); and UNC HealthCare).  
The trial involves an evidence based 8-week medical group mindfulness clinical pain program 
(OPTIMUM) modeled on Mindfulness Based Stress Reduction (MBSR) and delivered in 
primary care settings through a telehealth and videoconferencing format at the three different 
healthcare sites. 
A sample of 450 patients with chronic low back pain (cLBP) will be randomized to either 
OPTIMUM or to primary care provider (PCP) usual care. The PEG will be the primary outcome 
measure, which is a composite measure of pain and function. Secondary outcomes of 
psychological function will also be self-report. Health care system utilization will be obtained 
through the electronic health record (EHR) and includes opioid prescriptions, imaging, ED visits, 
and hospitalizations. We will also measure patient, clinic staff, and PCP satisfaction with 
OPTIMUM. 
Interventions and Duration  
Using Mindfulness to treat chronic low back pain in primary care settings. Patients will 
meet virtually via ZOOM (a video-conference application) weekly, for 8 weeks for 90 minutes in 
a group. Prior to the start of the intervention, patients meet one on one (approximately a 5-10 
minute telehealth visit) with the clinician who is co-facilitating and may be billing for the 
medical care provided during the telehealth visit. Currently, only Boston Medical Center is 
billing. Neither UNC or Pittsburgh sites are billing. Patients will be encouraged to see their PCP 
at the beginning and end of the program. Measures to determine the impact of OPTIMUM in the 
real-world setting will be obtained at baseline (T1), program completion (T2) and six and 12 
months after program completion (T3 and T4). The main outcome time point will be at six 
months (T3), which allows time for durability of effects to be determined. Participants will also 
complete monthly assessments of the pain medications they take and their health care system 
encounters.  
Total length of time each participant will be in study: 12 months. 
Sample Size and Population  
Our target sample size of 450 patients with cLBP ≥ 18 years of age will be individually 
randomized either to an 1) 8-week mindfulness clinical pain program (n=225) + PCP Usual Care 
or 2) PCP Usual Care (n=225). 
To ensure balance between groups, we will use permuted block randomization with block size of 
4 or 6, in a 1:1 ratio, stratified by clinic and sex. 

 
Study Product Guidelines and Considerations 
12 of 57 
Version 1.1 
 
 
13 November 2020 
1. STUDY OBJECTIVES 
1.1 Primary Objective 
Specific Aims of the study are:  
Aim 1: To integrate and test an evidence-based mindfulness clinical pain program, 
OPTIMUM, for patients with cLBP in the primary care setting. 
 
Primary Hypothesis: Patients in OPTIMUM will have significantly improved pain intensity and 
interference as measured by the PEG composite score at completion of the program and 6 
months (primary end point) and 12-months later, as compared to PCP Usual Care. 
Hypothesis 2: Patients in OPTIMUM will have significantly improved psychological function as 
measured by the PROMIS-29 Mental Health Summary Scale at completion of the program and 
6-and 12-months later, as compared to PCP Usual Care. 
Hypothesis 3: Patients in OPTIMUM will be less likely to start and more likely to reduce or stop 
an opioid prescription for cLBP as compared to those in PCP Usual Care. 
 
1.2 Secondary Objectives 
Aim 2: To evaluate use of healthcare resources by patients as documented in the EHR.  
 
Hypothesis: Patients in OPTIMUM will have fewer emergency department visits, fewer 
hospitalizations, fewer imaging procedures (CT/MRI), and fewer procedures (injections, surgery) 
than PCP usual care. 
 
Aim 3: To evaluate PCP and practice site use of, satisfaction with, and integration of 
OPTIMUM. 
2. BACKGROUND AND RATIONALE 
2.1 Background on Condition: 
Chronic pain is one of the most common conditions treated in the primary care setting, with 
cLBP costing over 30 billion dollars a year; yet treatment remains unsatisfactory for many 
patients.1 The slippery slope of opioids to treat cLBP has many unintended consequences such as 
addiction, overdose, and diversion.2,3 Compounding the problem, Primary Care Providers (PCP) 
have very little time during the 15-20 minute office visit to address the complex psychosocial 
and functional needs of the person with cLBP.4 The opioid crisis has underscored the urgency of 
alleviating patients’ cLBP with effective therapies, including evidence-based non 
pharmacological approaches that also address biopsychosocial needs. Mindfulness is effective 
for the treatment of cLBP yet remains underutilized as it has not been regularly woven into the 
outpatient clinical setting and is not reimbursed by health insurance companies.5, 6 Mindfulness-
based Stress Reduction (MBSR) is now part of the evidence-based guidelines of the American 
College of Physicians for initial treatment of cLBP.7 We have shown that an 8-week program 
modeled on MBSR decreased pain and increased short-term function in older adults with cLBP.5 
 

 
Study Product Guidelines and Considerations 
13 of 57 
Version 1.1 
 
 
13 November 2020 
The burden of chronic low back pain: Chronic low back pain (cLBP) affects an estimated 5-
10% of U.S. adults.8 The National Ambulatory Medical Care Survey has found that low back 
pain symptoms are the 10th most common reason for a patient office visit.9 The 2011 Institute of 
Medicine (IOM) report, Relieving Pain in America, highlights that low back pain (LBP) is the 
most common type of pain and the second most common reason that patients visit their primary 
care providers (PCP).10 Patients have high levels of satisfaction with their providers but are less 
satisfied with the outcomes of cLBP treatment.11 The PCP may escalate to opiates in the hopes of 
achieving satisfactory pain control despite the lack of evidence of their long-term benefit in 
cLBP.12,13 The opiate crisis has spurred the need for non-pharmacological options for cLBP 
management. In response to this need the American College of Physicians updated their 
evidence-based guidelines for the treatment of cLBP in 2017.7 They recommended that initial 
treatment be non-pharmacological, including mindfulness-based stress reduction (MBSR). 
However, many of these therapies are not yet widely available or are underutilized. To address 
this need, we are proposing an evidence-based, non-pharmacological clinical pain program for 
patients with cLBP delivered out of the primary care office. 
 
Evidence base for a group mindfulness pain program: Two recent large clinical trials have 
demonstrated the beneficial effects of mindfulness in improving pain and function in adults with 
cLBP. Our randomized clinical trial (RCT) of MBSR vs. an education control of 282 older adults 
with cLBP found clinically and statistically significant improvement in pain and physical 
function at program completion.5 Cherkin et al. randomized 342 adults to cognitive behavioral 
therapy (CBT), an 8-week MBSR program or usual care.6 CBT and MBSR both showed 
clinically significant improved function (30% improvement from baseline) 28-weeks after 
program completion as compared to usual care (57.7% and 60.5% vs. 44.1% respectively, overall 
P=.04). These studies have withstood the rigorous evaluation of meta-analyses. As a result, in 
addition to the American College of Physicians’ (the main professional organization for internal 
medicine) recommendation of MBSR as the initial treatment (along with 12 other non-
pharmacological therapies) for cLBP, the Agency for Healthcare Research and Quality also 
recommended MBSR for the treatment of cLBP in their recent comprehensive systematic 
review.7,14 While these landmark studies demonstrate the efficacy of the intervention, they were 
conducted under the controlled environment of a clinical trial. Translating the intervention to the 
clinical setting is the crucial next step for integrating the program into the “real world”. 
 
The value of group delivered self-management support in primary care: Common chronic 
diseases seen in a PCP’s office such as hypertension, diabetes, obesity, and cLBP all require 
extensive patient education. Yet the time constraint of a typical 15- or 20-minute visit only 
allows the PCP to provide cursory advice. Medical group visits (MGV) in the primary care 
setting with patients who have a chronic disease are an efficient and effective way to 
communicate, provide support, advice and education.15 For example, Cleveland Clinic offers 
over 200 types of shared medical appointments, Kaiser and Harvard Vanguard health systems all 
offer MGVs. Offering a group mindfulness pain program is an ideal opportunity to provide an 
evidence-based program to patients, which teaches them skills to learn to cope with and improve 
their pain and function without the use of opioids. Our program, modeled on MBSR, provides 
ample opportunity for discussion, allowing time to clarify misconceptions around chronic pain. 
Our proposal is in line with the 2011 Institute of Medicine Report “Relieving Pain in America” 

 
Study Product Guidelines and Considerations 
14 of 57 
Version 1.1 
 
 
13 November 2020 
which calls for new models of care for patients with chronic pain as we are embedding the 
program directly in the clinic.10  
 
Medical Group Visits: Current studies suggest MGVs improve health status indicators such as 
health-related quality of life, patient satisfaction, and patient trust in their physician, as well as 
improving coordination and culturally competent care.16, 17 MGVs can also reduce costs through 
the reduction of preventable emergency department (ED) visits and hospitalizations.18-21 MGVs 
are organized in many different ways, and no one best model has been demonstrated in the 
literature. MGVs include individual medical attention, teaching (didactic and interactive), and 
patient self-management. Groups range from 4-20 patients with one to two facilitators and meet 
at regular intervals–anywhere from weekly to monthly and from one to four hours. The 
clinician’s assessment and management can be conducted in an adjacent private examining 
space, and clinicians charge for the visit using established patient reimbursement codes. 
Integrative MGVs are also emerging for underserved populations.22-24 
 
Interest in mindfulness is widespread and growing in the United States: It is estimated that 
18 million Americans use meditation for health.25 In our experience, patients have been 
enthusiastic about learning mindfulness meditation and mind-body methods. In Pittsburgh alone, 
over 800 people have taken the fee-for-service MBSR program offered by the UPMC Center for 
Integrative Medicine. In Chapel Hill, NC the University of North Carolina (UNC) Program on 
Integrative Medicine’s Mindfulness-based Stress and Pain Management Program has taught 
year-round community-based fee-for service courses since 2000. For Dr. Morone’s mindfulness 
R01 study for cLBP, over 1,000 people called with interest in participating. We believe the local 
interest in mind-body methods reflects the national interest in mind-body medicine. By providing 
a convenient, evidence-based group mindfulness pain program in primary care, we propose to 
parlay that interest into improved access to the program, and thus, to improved health. 
2.2 Rationale 
The rationale for a medical group pain program that is mindfulness-based: PCPs are in 
need of more non-pharmacological treatment options for their cLBP patients instead of falling 
back on medications (acetaminophen and nonsteroidal anti-inflammatory drugs [NSAIDs]) and 
referring out for treatment or prescribing opiates. The current model of caring for chronic pain 
patients does not allow for the time and attention that PCPs need to adequately address the 
complex needs of their patients. The medical group model increases patient education, social 
support, access to a clinician, and a sustainable way to bill for the treatment. Our proposed 
project will address the need for non-pharmacological treatments for cLBP in the following way; 
a) the mindfulness pain program will be delivered in the primary care setting so that PCPs have 
another evidence-based therapy to offer patients; b) the mindfulness pain program provides the 
time and attention that is necessary to adequately educate patients about chronic pain; c) the 
medical group model provides for a reimbursable model of care. 
 
Impact: By translating an evidence-based group mindfulness pain program to the primary care 
setting we will 1) inform clinicians, patients, administrators and policy-makers how a medical 
group-based mindfulness pain program can be embedded into clinical practice; 2) determine the 
impact of this intervention under usual care circumstances; 3) demonstrate how the mindfulness 
pain program can be embedded in a variety of Health Care Systems; 4) demonstrate how the 

 
Study Product Guidelines and Considerations 
15 of 57 
Version 1.1 
 
 
13 November 2020 
mindfulness pain program can be delivered to an underserved population, which we expect will 
make up at least 2/3 of our total sample; 5) provide PCPs with more evidence based non-opioid, 
non-pharmacological therapies to treat their cLBP patients, which is currently limited to writing 
prescriptions for medications and referring out to other providers; 6) expand the access and 
availability of evidence-based treatments to patients with cLBP, who otherwise may not be able 
to participate in an integrative mindfulness pain program; and 7) signal to patients that pain 
management is important, by delivering services in their local primary care clinic locations. 
3. STUDY DESIGN 
It is a Pragmatic Clinical Trial (PCT) which will be conducted with four health care system 
(HCS) sites (Boston Medical Center, MA, a safety net health system; UPMC, Pittsburgh, PA, a 
large health system; Piedmont Health Services, NC, a network of federally funded health centers 
and UNC HealthCare, both in partnership with the University of North Carolina (UNC), Chapel 
Hill). The primary goal is to determine the impact of this intervention under usual care 
circumstances as defined in the FOA (vs. implementation research). The long-term goal is to 
increase the accessibility of evidence-based mindfulness programs to primary care patients with 
chronic pain. 
 
This study involves an evidence-based 8-week medical group mindfulness clinical pain program 
(OPTIMUM) modeled on MBSR and delivered in primary care settings through a telehealth 
videoconferencing format. We will randomize 450 patients with cLBP to either OPTIMUM or to 
PCP usual care. Patients will meet virtually via HIPAA-compliant ZOOM for 8-weeks for 120 
minutes in a group.  Prior to the start of the intervention, patients virtually meet one on one 
(approximately 10 minutes) with the clinician who is co-facilitating and billing for the medical 
care provided (via telehealth). Measures to determine the impact of OPTIMUM in the real-world 
setting will be obtained at baseline (T1), program completion (T2) and six and 12 months after 
program completion (T3 and T4). The main outcome time point will be at six months (T3), 
which allows time for durability of effects to be determined. Participants will also complete 
monthly assessments of the pain medications they take and their health care system encounters.  
Pain intensity (PEG composite score) at six months will be the main outcome measure (obtained 
through online self-report surveys). Secondary outcome of psychological function will also be 
self-report and obtained online, or if the patient prefers, by telephone. Health care system 
utilization will be obtained through the EHR and includes opioid prescriptions, imaging, ED 
visits, outpatient primary care visits, physical therapy visits, injections, and hospitalizations. We 
will also measure patient, clinic staff, and PCP satisfaction with OPTIMUM. Totally, 
participants will remain in the trial for 12 months including the follow-up period.  
4. SELECTION AND ENROLLMENT OF PARTICIPANTS  
Our target sample size of 450 patients with cLBP ≥ 18 years of age will be individually 
randomized either to a 1) 8-week mindfulness clinical pain program (n=225) + PCP Usual Care 
or 2) PCP Usual Care (n=225). The selection criteria are kept broad to include most patients 
referred to the PCT.  
4.1 Inclusion Criteria 
Participants must meet all of the inclusion criteria to participate in the trial. 

 
Study Product Guidelines and Considerations 
16 of 57 
Version 1.1 
 
 
13 November 2020 
• Age ≥ 18 
• Chronic low back pain, which is pain that persists for at least 3-months and has resulted 
in pain on at least half the days in the past 6 months 
• A score ≥ 3 on the PEG 
• Willing and able to provide online or telephone informed consent 
• Speak English as the intervention manual is currently written in English 
4.2 Exclusion Criteria 
Participants meeting the exclusion criteria at baseline will be excluded from the trial.  
• Do not meet the above inclusion criteria 
• Red flags- recent (past month) worsening of pain, unexplained fever, unexplained weight 
loss  
• Pregnancy  
• Metastatic cancer 
• First degree relatives (parents, siblings, child) of someone who has participated or is 
participating in the OPTIMUM study 
• Members of the same household  
• Not a patient at a participating clinic or persons not planning to continue as a patient at a 
participating clinic for 12 or more months 
1.  Study Enrollment Procedures  
The HCS sites that were chosen represent diversity in practice delivery and in-patient population. 
We expect a full 2/3 of our sample will be underserved and/or an underrepresented group. 
Multiple approaches will be used at all three HCS sites to recruit participants into the PCT. 
Detailed recruitment procedures are in the Standard Operating Procedures document. Some of 
the approaches are described here. The electronic health record will be reviewed each week for 
patients with a diagnosis of low back pain who have an upcoming appointment, once identified, 
patients will be approached by the study research assistant, with consent of the provider, for 
screening for study eligibility. Patients will also be informed of the program by a letter from their 
PCP or clinic administrator (e.g. Medical Director, healthcare system administrator) which will 
also invite them to participate. Flyers and rack cards describing the program will be placed 
throughout the clinics. Referral at the point of care may occur by creating an order in the EHR 
that will refer patients to OPTIMUM. This workflow is well established at UPMC and BMC and 
will be integrated into the EHR at PHS.All four HCSs use an EHR. BMC, UPMC, and UNC 
Healhcare use EpicCare (Epic), one of the most common EHRs, now deployed in an estimated 
35% of healthcare systems in the United States. PHS uses Centricity. The different EHRs used 
are seen as a strength as it will demonstrate integration of OPTIMUM into different EHRs. Each 
site will have the opportunity to customize recruitment in order to fit the unique needs of each 
HCS. For example, UPMC may create an electronic alert which would pop-up when clinicians 

 
Study Product Guidelines and Considerations 
17 of 57 
Version 1.1 
 
 
13 November 2020 
were seeing a patient with LBP. If the patient is interested, the clinician would click to refer the 
patient to OPTIMUM. 
Randomization procedure: To ensure balance between groups, we will use permuted block 
randomization with block size of 4 or 6, in a 1:1 ratio, stratified by clinic and sex.  
5. STUDY INTERVENTIONS  
5.1 Interventions, Administration, and Duration  
OPTIMUM: The medical group mindfulness clinical pain program will retain the format, 
meditation exercises and discussions about the mind-body connection and pain of the original 
program we studied, which was modeled on the MBSR program that we successfully delivered 
to older adults with cLBP.5 The program teaches a variety of mindfulness meditation methods. 
Mindfulness meditation is simple and safe because it takes ordinary activities like breathing, 
eating, and walking and turns them into a meditation by creating greater awareness of the 
moment-to-moment sensations, emotions, thoughts and behaviors that arise during these 
activities.52 The program will incorporate several modifications we made during the large clinical 
trial to tailor it to the patient with cLBP. This included understanding pain from a mind-body 
perspective, and viewing pain as a stressor on physical sensations, thoughts, emotions, and 
behavior. It also included discussion on patients’ use of mindfulness to work with pain and pain-
themed meditations. 
Program Protocol: We are following the evidence-based protocol used in our large clinical trial 
of MBSR for cLBP. Both this trial and our pilot work used similar formats. Both these trials 
were included in the evidence-base of MBSR for cLBP by the American College of 
Physicians.5,7,26  
During the first week participants will be introduced to the principles and practice of mindfulness 
meditation. The homework requirement of daily meditation (six of seven days/week) lasting 5-45 
minutes will be reviewed. Support materials of downloadable MP3, MP3 player with uploaded 
guided meditations, YouTube link to the guided meditations or CD recording and reading 
materials will be distributed. As a result of the pilot, the YouTube link works best, it is a private 
link that cannot be found by searching YouTube, participants are emailed the link. The body 
scan technique will be taught at the first session. If physical discomfort should arise during any 
meditation, participants will be encouraged to change to a more comfortable position. The first 
class introduces mindful eating, which is done through a guided exercise of eating a raisin (or 
other food at meditation instructor’s discretion). This exercise begins to introduce the concept of 
informal meditation, in that mindfulness can be brought to everyday activities like eating. 
During the second and following weeks the sessions will include a general discussion of the 
patients’ experience with the meditation method, including problem-solving regarding obstacles 
to the meditation practice. Theoretical material related to meditation, pain and the mind-body 
connection will be presented. About 30 minutes will be spent at each session in these 
discussions. Also during the second week, quiet sitting meditation with mindfulness of breathing 
will be introduced. Gentle chair-based stretching exercises are introduced at the second class 
(i.e., mindful stretching). The third session will introduce pain theory and the multidimensional 
response to pain.  The role of expectation will be reviewed. 

 
Study Product Guidelines and Considerations 
18 of 57 
Version 1.1 
 
 
13 November 2020 
The fourth session will introduce the flight or fight reaction. This is an interactive session with 
participants describing their reactivity to stress as well as their response to mindfulness 
meditation. Stress and the relaxation response will be discussed in relation to worsening or 
decreasing pain.  
At the fifth week’s session, walking meditation or mindful movement may be introduced. How to 
use mindfulness meditation methods to work with pain will be discussed. This will occur at this 
and the sixth session. Participants will also be taught how to work with pain during formal 
meditation. They will learn this by a guided meditation during this session, as well as a recording 
of the body scan that is specific for working with pain.  
At the sixth week’s session, mindfulness in interpersonal relationships and everyday life will be 
discussed. There will be a review of using mindfulness methods to work with pain, as well as 
interactive discussion of participants’ use of mindfulness to work with pain. 
At the seventh week’s session, using mindful attention to perceive the choices that are available 
at this moment, and that can affect our pain, health, and well-being will be discussed.  
The eight week’s session will include discussion of the application of mindfulness to everyday 
situations as well as breaking through habitual tendencies of coping with pain. Integrating what 
has been learned over the course of the program will be reviewed.  
All sessions may include yoga. 
Mindfulness instructors have flexibility to review content in a different order so that they can 
customize their instruction to the participants. 
 
The structure of each session will be approximately 45 minutes (total) of meditation and 45 
minutes of discussion. This format was applied successfully during our large clinical trial.5 
 
PCP Usual Care Control: PCP Usual Care was chosen as the comparator as it is currently the 
most commonly used treatment option for patients with cLBP. We will verify patients’ 
attendance at a PCP visit during the study through the EHR as well as the meditation instructor 
taking attendance. Participants in the PCP usual care control group will be given the option to 
receive the OPTIMUM mindfulness pain management program at the end of their participation 
in the study.  
 
Frequency, setting and providers: Participants will be seen in a group format virtually via 
HIPAA compliant ZOOM once a week for 120 minutes for 8-weeks.  Group size will be 
approximately 5-12 patients per session. We found this group size to be optimal in both our pilot 
work and large clinical trial because the group was small enough to encourage individual 
participation, but not too large that participants were afraid to speak. This is also consistent with 
group size for MGVs. The original and proposed group mindfulness pain program is modeled on 
the MBSR program we successfully delivered to older adults with cLBP5. All sessions will be led 
by a clinic-based provider (MD or DO, nurse practitioner, physician assistant, social work 
therapist, or psychologist) to whom we provide training in co-leading the program, as well as an 
experienced MBSR instructor. Training at the three HCS sites will consist of several one-hour 
sessions facilitated by Dr. Gardiner. We have chosen this model because the clinic-based 
provider will be able to schedule patients under their name, document in the medical record, 
provide face-to-face time, and bill for the sessions. The MBSR instructor has the necessary 
expertise to teach the program. We will use materials that have been previously developed for 
MGV provider training and adapt them to OPTIMUM. These materials will be used for wider 

 
Study Product Guidelines and Considerations 
19 of 57 
Version 1.1 
 
 
13 November 2020 
dissemination. All sessions will occur in a HIPPA compliant  version of ZOOM (video-
conference application).  
Technical Training: All participants will receive technology training on using 
videoconferencing during a one hour session. The intervention will require technology support. 
Details of the technical training and technical support during the intervention sessions is detailed 
in the Technical Training and Support Standard Operating Procedures. 
5.2 Handling of Study Interventions  
Three methods of mindfulness meditation will be taught, consisting of: 1) the body scan; 2) 
sitting practice/awareness of breathing; 3) mindful movement/yoga. An instructor manual has 
been created to guide the providers at all three HCS sites.  
5.3 Concomitant Interventions  
5.3.1 Allowed Interventions 
OPTIMUM medical group mindfulness clinical pain program.  
5.3.2 Required Interventions 
None. 
5.3.3 Prohibited Interventions 
None.  
5.4 Adherence Assessment  
Assessment and monitoring: Attendance at group sessions will be obtained through the EHR 
(registered appointment) as patients will need to check in as a telehealth visit and that check-in is 
logged into the EHR. Unblinded study staff will record attendance.  Adherence-promoting 
strategies include providing guided meditation recordings and instructional materials. Group 
sessions will stress the importance of home practice and group participation, and discussion will 
include problem-solving around barriers to the meditation practice and coping with pain. 
Treatment fidelity and credibility: The mindfulness instructors will meet weekly during the 
first 6-months of the UH3 phase of the trial along with Dr. Morone, Dr. Gaylord, and Dr. 
Gardiner to discuss the delivery of the program in primary care through a telehealth video 
format, review the structure and format of the sessions, and troubleshoot barriers as they arise. 
After the first 6-months meetings will be biweekly and starting in Year 2 of the UH3 will be 
monthly. More frequent or less frequent meetings will be at the discretion of the group. It is 
critical during this demonstration project to meet regularly to address issues of program delivery 
and integration into clinic.  Additionally, Dr. Greco has been trained in the use of the 
Mindfulness-based Interventions-Teaching Assessment Criteria (MBI-TAC), a standardized 
system for rating competency of mindfulness instructors and she will be able to provide guidance 
on evaluating treatment fidelity in a pragmatic setting. Training and monitoring at the three HCS 
sites will consist of: 1) a combined 3-hour online MGV training led by the respective site PIs and 
facilitated by Dr. Gardiner; 2) weekly to monthly meetings, as noted above; and 3) facilitator 
evaluation and group fidelity monitoring, led by Dr. Greco. 

 
Study Product Guidelines and Considerations 
20 of 57 
Version 1.1 
 
 
13 November 2020 
 
 
6. STUDY PROCEDURES  
6.1 Schedule of Evaluations (Table 1) 
 
Assessment 
Screening & 
Consent 
Baseline  
(T1) 
OPTIMUM 
Program 1-8 
weeks, End of 8 
weeks 
(T2) 
Monthly Pain 
Medication and 
Healthcare 
Encounters 
Follow-up after 6 
months 
(T3) 
Follow-u
mo
(T
Informed Consent 
Form   
X 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Screening 
Questionnaire 
X 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
  
 
 
 
 
Enrollment/Randomiz
ation 
X 
 
 
 
 
 
Adverse Events 
 
 
X 
 
X 
X
Study Measures 
 
X 
X 
X 
X 
X
 
 
 
 
 
 
 
 
6.2 Description of Evaluations  
6.2.1 Screening Evaluation 
Procedures to determine whether a potential participant is eligible to take part in the trial are 
known as screening procedures.  
 
Consenting Procedure 
 
We have requested and received IRB approval for a waiver of the requirement to obtain a signed, 
written informed consent for the preliminary screening procedures used to determine the 
eligibility of potential participants. Screening will occur over the phone and an IRB approved 
script will be used, followed by the screening questionnaire.  
 
In person screening: After the COVID pandemic, in-person screening procedures may occur 
since potential participants can be identified before their visit through medical record review. 
When potentially eligible patients are identified before their upcoming in person office visit 

 
Study Product Guidelines and Considerations 
21 of 57 
Version 1.1 
 
 
13 November 2020 
because they have a low back pain diagnosis, they will be approached ONLY if their provider 
agrees. They will be asked if they would be interested in hearing about the study, some brief 
eligibility questions and if they are eligible, would they like to hear more about the study. This 
will count as verbal consent (IRB approved script will be followed) for the preliminary screening 
procedure Since, the screening procedures consist only of the basic information from interested 
potential participants, we believe it is conventional to defer obtaining written informed consent. 
 
Informed consent: We have obtained IRB permission to obtain verbal informed consent, 
obtained through a telephone interview. After the screening procedure, eligible participants will 
be provided with a copy of informed consent through email. All will be encouraged to review the 
consent form before undergoing informed consent. A listed investigator or designated study team 
member trained in informed consent will obtain informed consent from each study participant 
before the start of any research/intervention procedures. A page-by-page review of the consent 
form will occur and the potential study subject will be asked for a verbal indication of their 
understanding of the material contained in the consent form. They will also be asked if they have 
any questions. Participants will then be asked to verbally consent, if they agree with the material 
and wish to be enrolled in the study.  The potential participants may reschedule their enrollment 
visit should they feel that they need more time to decide about enrollment.  
 
We will also administer an electronic informed consent for subjects who wish to complete the 
procedure online and not over the telephone.  
 
Screening  
Screening will be established by telephone. Participants will undergo screening if they are 
identified  in EPIC (Electronic Health Record System) or they self-refer as a result of having 
heard about the trial from the HCS sites research registry, clinician referral or posted flyers or if 
they receive a letter from their provider to participate in the study. Recruitment will also occur 
by using the Clinical Data Warehouse at Boston Medical Center that allows for identifying 
patients with a diagnosis of low back pain. At the University of Pittsburgh a similar process is 
available through the University of Pittsburgh CTSI. Additionally, all sites may use research 
registries to identify subjects. Screening includes questions designed to inform potential 
participants about the study and help the study team in determining whether he/she is initially 
eligible. This procedure takes approximately 6-10 minutes to complete.  
 
Potential participants will be informed about the eligibility during the screening procedure.  
  
Because the intervention is delivered in cohorts, if there has been more than an 8-week delay 
between screening and the start of the cohort, then the participant will be rescreened for 
eligibility with the PEG. If the score is < 3 they will be ineligible. 

 
Study Product Guidelines and Considerations 
22 of 57 
Version 1.1 
 
 
13 November 2020 
6.2.2 Enrollment, Baseline, and/or Randomization 
Enrollment 
Enrollment in the trials refers to the stage when participant is completely eligible, has given 
informed consent, completed the required screening and demographics and has been randomized. 
Randomization will occur after the baseline assessment. 
Baseline Assessments and Study Measures 
Once informed consent has been obtained and eligibility confirmed baseline measures will be 
completed. The baseline and subsequent assessments (T1-T4 and monthly assessments) will be 
completed electronically or over the telephone, per patient preference. We will also mail the 
measures to patients if that is the only way they will complete the measures. A self-addressed, 
stamped envelope will be included.  
Assessing improvement in a patient’s chronic pain condition is challenging because unlike 
diabetes, hypertension, or obesity there is not yet bloodwork or objective measurements that can 
be easily ordered or obtained. PCPs thus rely on self-report of improvement that may or may not 
involve a scale. The CDC’s guidelines for the prescription of opioids for chronic pain provide 
recommendations for pain evaluation and treatment that inform our outcomes.  The CDC 
guidelines include evaluating the multidimensional impact of chronic pain with validated scales 
that measure pain intensity, function (in its broader sense to include physical, emotional and 
social function or quality of life), mood, sleep, pain catastrophizing, and anxiety.59 Additionally, 
they reiterate that a 30% improvement in pain and function is clinically meaningful. A recent 
comprehensive review of measures to include in chronic pain trials recommended the PEG 
composite score, PROMIS 4-item function (obtained from the PROMIS 29) and scales for 
evaluating mood, anxiety, and global impression of change. To avaluate the association between 
pain and trauma, we have added the Life Events Checklist for DSM-5 (LEC-5). We have 
followed these recommendations for the patient-reported outcomes (PRO) measures as shown in 
Table 3. Given these recommendations, as well as the well-established use of the PEG composite 
score in clinical practice and its low patient burden we will use the PEG composite score as the 
primary outcome measure. Because administering these measures is not part of usual care, 
except for the PEG composite score, we will capture PROs directly from patients during four key 
time points of the PCT.     
 
We will obtain healthcare resource utilization directly from the EHR (Table 3). The EHR will 
evaluate opioids according to prescriptions written; CT/MRIs performed; invasive procedures 
such as injections and surgeries; outpatient primary care visits, physical therapy visits, urgent 
care visits, ED visits, and hospitalizations.  Most utilization outcomes will be treated as count 
data and cumulative opioid exposure as continuous (i.e., cumulative morphine equivalents).  
        
All 450 participants who are included based upon the screening criteria outlined above will 
receive identical assessments. We will use a paperless data management system that is described 
below. The measures are quick to administer and complete. In our experience, almost all the 
individual measures can be done in 5 minutes or less. The total time for assessment is expected 
to be 20 minutes, with many people completing measures in less time.  
 

 
Study Product Guidelines and Considerations 
23 of 57 
Version 1.1 
 
 
13 November 2020 
We will also conduct an online survey with all PCPs in the participating practice, to learn about 
their perspectives on how well the study procedures integrated with their work flow, overcame 
common barriers to chronic pain management, and were consistent with the practice’s typical 
referral and feedback protocols. This survey will also ask PCPs to report if/how many of their 
patients enrolled raised safety concerns during the study, overall satisfaction with the program, 
and open-ended questions will solicit feedback for protocol improvements. 
 
Outcome Measures Table (Table 2) 
 
 
T1 
Baseline 
 T2 
  8-wks 
*T3    
 6-mo 
T4      
12-mo 
Number of 
Questions 
Patient-reported Measures 
**PEG 
X 
X 
X 
X 
3 
PROMIS-29 (Q.1-4 & 17-20 same as 
PROMIS Physical Function & PROMIS 
Sleep 
X 
X 
X 
X 
29 
Current Opioid Misuse Measure 
X 
X 
X 
X 
17 
CAMS-R (mindfulness) 
X 
X 
X 
X 
12 
Satisfaction, single item 
 
X 
X 
X 
1 
Ethics, single item 
 
X 
 
 
1 
Patient Global Impression of Change 
PGIC 
 
X 
X 
X 
1 
Opioid Use, single item  
X 
X 
X 
X 
1 
Pain Catastrophizing Scale Short Form 
X 
X 
X 
X 
6 
Demographics 
X 
 
 
 
~23 
Tobacco, Alcohol, Prescription 
medications, and other Substance 
(TAPS).  
X 
 
 
X 
5 
Screening questionnaire 
X 
 
 
 
~10 
Pain Medication (s) This form will be 
asked monthly 
X 
X 
X 
X 
 
Charlson Co-Morbidity Index 
X 
 
 
 
23 

 
Study Product Guidelines and Considerations 
24 of 57 
Version 1.1 
 
 
13 November 2020 
Health Care System Utilization (self-
report). This form will be asked monthly 
 
X 
X 
X 
~20 
HEAL-Expectation 
X 
 
 
 
6 
Telehealth Usability Questionnaire 
X 
X 
 
 
7 
Total Questions OPTIMUM 
 
 
 
 
 (baseline) 
(other time points) 
Life Events Checklist for DSM-5 (LEC-
5), 
*This form will be asked once at any 
upcoming timepoint (including monthly 
assessments) 
 
* 
* 
* 
17 
Global Mindfulness 
 
 
 
X 
13  
EHR Outcomes 
Opioid prescriptions and other 
prescriptions for pain, CT/MRIs of 
lumbar-sacral spine, injections of 
lumbar-sacral spine, ED/urgent care 
visits for LBP, Surgeries of lumbar spine, 
hospitalizations for LBP, PCP visits for 
LBP, physical therapy referrals for LBP 
X 
 
X 
X 
Core HEAL Pain Data Measures  
PROMIS Physical Function (questions 1-
4 same as in PROMIS 29 questions 1-4) 
X 
 
X 
 
2 additional 
questions  
PROMIS Sleep (questions 1-4 same as in 
PROMIS 29 questions 17-20) 
X 
 
X 
 
2 additional 
questions 
Sleep Disturbance 
X 
 
X 
 
2 
Depression PHQ-2 
X 
 
X 
 
2 
Anxiety GAD-2 
X 
 
X 
 
2 

 
Study Product Guidelines and Considerations 
25 of 57 
Version 1.1 
 
 
13 November 2020 
*Primary Timepoint **Primary outcome. 
Pain impact is defined as Pain intensity, pain interference and functional status calculated from 9 items 
of the PROMIS-29. PROMIS: patient reported outcomes measurement information system.   
Yellow Highlight=Core HEAL Measures incorporating into OPTIMUM outcomes. 
 
 
Additional Baseline Variables: We will assess age, sex, race, ethnicity, and socioeconomic 
status, involvement in workers’ compensation, work status, previous treatment including 
nonpharmacological therapies, and marital and educational status. Biomedical factors will 
include: a) comorbidity: data on comorbidity will be gathered using the Charlson Co-Morbidity 
Index T1;60 b) pain medications (regularly scheduled and as-needed) at T1-T4 and will be 
categorized into sub-classes:  i) salicylates (aspirin > 1200 mg/day, salsalate); ii) non-aspirin, 
non-COX2 selective NSAIDs; ii) COX2 selective NSAIDs; iv) acetaminophen; v) opioids; vi) 
skeletal muscle relaxants; vii) adjunctive agents (e.g., corticosteroids, capsaicin, Neurontin); and 
c) antidepressants and antianxiety medications. Regularly scheduled opioid analgesics will be 
converted to daily oral morphine equivalents.61  
Randomization 
To ensure balance between groups, we will use permuted block randomization with block size of 
4 or 6, in a 1:1 ratio, stratified by clinic and sex. Participants will be randomized after completion 
of baseline measures. 
6.2.3 Blinding 
This is a double-blinded study as research assistants who assist participants in their assessments 
and the study statistician will be blinded to treatment assignment. Participants will not be blinded 
to group assignment. Detailed table below. 
 
Study Staff 
Blinding: Justification 
Principal Investigator (PI) 
Unblinded: Any AEs that occur need to be reported and 
reviewed. Can serve as back-up for mindfulness instructor or 
provider 
Site Co-Principal Investigator  
Site Co-Principal Investigator 
Unblinded: Any AEs that occur need to be reported and 
reviewed. 
 
At UNC one site co-PI is blinded due to involvement with 
EHR data and programming local REDCap 
Co-Investigators (Co-I) 
Blinded 
Project Manager 
Unblinded: Needs to interact with all staff, point of contact for 
AEs along with PI, randomizes participants 

 
Study Product Guidelines and Considerations 
26 of 57 
Version 1.1 
 
 
13 November 2020 
Study Coordinator 
Not all sites have separate study coordinators-UNC only.  One 
will be blinded and the other will be unblinded because she is 
the technology assistant for the intervention 
Research Assistants 
Blinded 
Biostatistician 
Blinded 
Data Analyst 
Blinded 
Programmer 
Unblinded: will need to respond to requests which may 
involve randomization status 
 
 
6.2.4 Follow up Visits 
All outcomes will be assessed at program completion and after six and twelve additional months 
of follow-up (eight weeks (T2), six months (T3), and twelve months (T4) from the start of the 
program, respectively), except satisfaction with OPTIMUM and Global Impression of Change, 
which will be assessed at program completion and at the six months and twelve months 
timepoints (T2, T3 & T4) Moreover, pain medications and healthcare utilization form will be 
assessed every month. Study participants will each be enrolled for up to twelve months. Follow-
up for twelve months was chosen to evaluate duration of program effect on patients’ cLBP.      
 
6.2.5 Completion/Final Evaluation 
Final Evaluation at twelve months (T4) will have the same assessments as at the end of the 
program (T2) and at six months (T3). 
7. SAFETY ASSESSMENTS  
We will monitor patient safety throughout 12 months of duration of the study. Potential risks of 
mindfulness interventions are minimal and may include the following:   
• Emotional discomfort or distress may arise for some participants during exercises or at 
home practice related to awareness of negative emotions, thoughts, or physical 
sensations. 
• Participants might face discomfort when sitting in a chair. 
• Participants might face discomfort when doing gentle chair exercises (chair yoga) 
 
Risks associated with mindfulness interventions are generally minimal and transient and can be 
managed with instructor guidance and continued experience with the practices. These risks will 
be explained to participants at study enrollment. An experienced mindfulness instructor will lead 
the sessions. Participants will be encouraged throughout the sessions to discuss their experiences 
with the exercises, including any emotional difficulties. Additionally, the beginning of each 
session will include time to discuss home practices and the participant will problem-solve with 
the instructor any issues that came up in practice during the week. Participants will be reminded 

 
Study Product Guidelines and Considerations 
27 of 57 
Version 1.1 
 
 
13 November 2020 
that the sessions are confidential in order to encourage disclosure of difficulties. For discomfort 
while sitting in a chair, participants will be instructed on how to be mindfully aware of 
discomfort and then to gently change position to one that is more comfortable. 
7.1 Specification of Safety Parameters 
Participants may experience discomfort in answering some of the questionnaire questions or in 
making disclosures in the sessions.  Participants will be told that they may skip questions that 
they do not wish to answer and that disclosures in the program are also entirely voluntary. All 
patients are advised to refrain from disclosing anything said during the sessions outside the 
group. 
7.2 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters 
In the two large studies of MBSR for chronic low back pain, no significant adverse events 
related to the intervention were reported.5,6 Given that mindfulness methods take ordinary 
activities like sitting down, eating, lying down and walking and turn them into a meditation 
through directed breathing, adverse events are rare. Any adverse event reported to the MBSR 
instructor will be recorded, reviewed by the PIs and reported to the IRB when unexpected and 
study-related, and all AEs whether expected, unexpected, study related or study unrelated will be 
reported to the independent monitoring committee. Any adverse event that results in patient 
injury or requires immediate medical attention will be brought to the attention of the study team 
and PIs immediately. The MBSR interventionists and study team will have immediate access to 
the PIs through pager or cell phone number. We will collect health care system encounters every 
month. Any positive responses will be explored by study personnel to obtain additional 
information. This will then be reviewed by the PIs.  
7.3 Adverse Events and Serious Adverse Events  
For determining severity of an adverse event we use the following definitions (below). If a 
participant has an emergency department visit (but not hospitalized and discharged to home), 
then they are assigned of moderate intensity and if the participant is hospitalized it is assigned of 
serious intensity. 
 
Adverse Event: any untoward medical occurrence (whether physical or psychological) 
associated with the use of meditation or mind and body methods, or breach of confidentiality and 
which may have a causal relationship with the study procedures. 
Mild: Awareness of signs or symptoms, but easily tolerated; are of minor irritant type; causing 
no loss of time from normal activities; symptoms would not require medication or a medical 
evaluation; signs and symptoms are transient. 
Moderate or greater severity. This adverse event requires medical evaluation and/or medical 
treatment; or is a serious adverse reaction. 
Serious. This adverse event is fatal or life-threatening; requires hospitalization; or produces a 
disability. 
 
Solicited adverse events and serious adverse events: will occur during the monthly assessments 
when health system utilization will be queried.  

 
Study Product Guidelines and Considerations 
28 of 57 
Version 1.1 
 
 
13 November 2020 
7.4 Reporting Procedures 
When participants report an AE or SAE a description of the AE will be recorded in REDCap and 
brought to the attention of the PI who will then determine if it is study related. Clinicians will 
make a note during the 8-week sessions, if any adverse effect comes up and report it to the study 
team who will record the event on the Important Medical Event Form and then notify the PI. Any 
unanticipated problems involving risk to subjects or others and study-related will be reported to 
IRB as per the University of Pittsburgh sIRB guidelines. (Refer to the “Adverse Event 
workflow” sheet for information on how and when to report AEs/SAEs or Unanticipated 
problems) 
7.5 Follow up for Adverse Events  
We will follow patients until the adverse event is resolved. 
7.6 Safety Monitoring  
A formal Independent Monitoring Committee will be set up which will follow the procedures of 
the NCCIH. 
8. INTERVENTION DISCONTINUATION  
Circumstance for Withdrawal without Consent: 
 
Withdrawal Procedures: Participants are permitted to withdraw from the study at any time during 
the intervention or follow-up process. To withdraw from the study, participants should contact 
the PI at the corresponding site. Participant data prior to withdrawal will be retained in the case 
of withdrawal from the study. 
9. STATISTICAL CONSIDERATIONS  
9.1 General Design Issues 
OPTIMUM is a multi-site Randomized Controlled Trial/ Pragmatic Clinical Trial (PCT) to treat 
chronic low back pain (cLBP) in primary medical settings using mindfulness through a telehealth 
HIPAA-compliant videoconferencing format  The study participants will be randomized at an 
individual level. 
Specific Aims of the study are 
Primary Objective, Aim 1: To integrate and test an evidence-based mindfulness clinical pain 
program, OPTIMUM, for patients with cLBP in the primary care setting. 
 
Primary Hypothesis: Patients in OPTIMUM will have significantly improved pain intensity and 
interference as measured by the PEG composite score at completion of the program and 6 
months (primary end point) and 12-months later, as compared to PCP Usual Care. 
Hypothesis 2: Patients in OPTIMUM will have significantly improved psychological function as 
measured by the PROMIS-29 Mental Health Summary Scale at completion of the program and 
6-and 12-months later, as compared to PCP Usual Care. 

 
Study Product Guidelines and Considerations 
29 of 57 
Version 1.1 
 
 
13 November 2020 
Hypothesis 3: Patients in OPTIMUM will be less likely to start and more likely to reduce or stop 
an opioid prescription for cLBP as compared to those in PCP Usual Care. 
 
Secondary Objective, Aim 2: To evaluate use of healthcare resources by patients as documented 
in the EHR.  
Hypothesis: Patients in OPTIMUM will have fewer emergency department visits, fewer 
hospitalizations, fewer imaging procedures (CT/MRI), and fewer procedures (injections, surgery) 
than PCP usual care.  
 
Secondary Objective, Aim 3: To evaluate PCP and practice site use of, satisfaction with, and 
integration of OPTIMUM. 
9.2 Sample Size and Randomization 
Our target sample size of 450 patients with cLBP ≥ 18 years of age will be individually 
randomized either to an 
1) 8-week mindfulness clinical pain program (n=225) + PCP Usual Care or  
2) PCP Usual Care (n=225). 
Randomization and Treatment Assignment Procedure 
To ensure balance between groups, we will use permuted block randomization with block size of 
4 or 6, in a 1:1 ratio, stratified by clinic and sex. Co-I Dr. Weinberg (lead statistician) will 
generate the randomization sequence using SAS version 9.4, which will be implemented in the 
database so that the group allocation will be revealed only when each patient consents and is 
randomized. The randomization schedule will be created prior to enrollment and the study 
statistician will remain blinded to treatment assignment.  We chose to randomize at the patient 
level rather than at the cluster level (provider or clinic) based on our responses to design choice 
clarification questions recommended by the NIH Collaboratory: 1) the impact of the pain 
program in the real-world setting is primarily at the level of the individual patient, as OPTIMUM 
is delivered to the patient and not the provider, for example, we are not studying implementation 
of provider treatment guidelines, which could result in contamination if randomized at the patient 
level 2) randomization at the patient level will not interfere with usual care for the patient with 
cLBP 3) contamination, if it occurs, will be minor. Contamination cannot be completely 
eliminated in either cluster or traditional RCT designs and we expect either design has a small 
risk of staff or patients discussing study details (“comparing notes”) as medical care is delivered 
in teams and patients go to a variety of clinics depending on appointments with specialists. 
Additionally, randomization at the patient level allows for efficient use of limited resources 
(reducing cost and time to completion of the study) while still including a large sample size and 
maintaining scientific rigor. 
9.3 Definition of Populations 
All analyses for treatment group comparisons will use the original treatment assignment as 
randomized for each participant (intention-to-treat).  We will also perform a per-protocol 
analysis for the primary outcome for participants who attended at least 6 out of 8 (75%) of 
sessions. 

 
Study Product Guidelines and Considerations 
30 of 57 
Version 1.1 
 
 
13 November 2020 
9.4 Interim Analyses and Stopping Rules 
The interim analyses and stopping rules will be assessed by the independent monitoring 
committee. 
 
This study will be stopped prior to its completion if (1) the intervention is associated with 
adverse effects that significantly impact the risk-benefit ratio; (2) study recruitment or retention 
becomes futile; (3) any new information becomes available during the trial that necessitates 
stopping the trial; or (4) other situations occur that might warrant stopping the trial. 
9.5 Outcomes  
9.5.1 Primary Outcome   
The PEG composite score is the primary outcome measure. This will be used to measure the pain 
intensity, interference, and enjoyment. Six months (T3) will be the primary time point.  
9.5.2 Secondary Outcomes   
Secondary outcomes are listed in Table 2 above. 
9.6 Data Analyses  
Data Evaluation: 
Prior to conducting the analyses outlined below, we will evaluate the statistical properties of our 
baseline information and outcome measures. Descriptive statistics, including measures of central 
tendency (means, medians, other percentiles) and dispersion (standard deviations, ranges) will be 
computed for continuous data such as the age at enrollment, PEG composite score and other 
continuous measures. We will also check for potential outliers, normality and missing data. 
Frequency distributions will be calculated for categorical data such as sex. 
We will compare the distributions of baseline characteristics between the two groups to assess 
the effectiveness of the randomization. All analyses for treatment group comparisons will use the 
original treatment assignment as randomized for each participant (intent-to-treat). We will adjust 
for any baseline variable that either statistically (based on a p-value cutoff of p<0.2) or clinically 
differs between the two groups. Data transformations may be applied to outcomes depending on 
the shape of the distribution to better approximate normality. We will consider ease of 
interpretation and clinical meaningfulness when choosing transformations. 
 
Aim 1: To integrate and test an evidence-based mindfulness clinical pain program, OPTIMUM, 
for patients with cLBP in the primary care setting. 
Primary Hypothesis: patients in OPTIMUM will have significantly improved pain intensity 
and interference as measured by the PEG composite score at completion of the program and 
6 months (primary end point) and 12-months later, as compared to PCP Usual Care.  
 
We will compare the PEG (primary outcome) at T2 (8 weeks from baseline) and T3 and T4 (6 
months and 12 months from T2) with PEG at T1 (baseline) included in the vector of repeated 
measures using a mixed effects model. We will include the intervention group indicator, time 

 
Study Product Guidelines and Considerations 
31 of 57 
Version 1.1 
 
 
13 November 2020 
and their interaction as fixed effects, with random effects for repeated measures on individuals 
over time and random class effects for group in the intervention arm. We are proposing to 
control for clustering effect within each class using a random effect because the response of 
participants in the same class might be correlated. In the study by Dr. Lynn DeBar, the intraclass 
correlation coefficient for the class was 0.053.5 We have also taken this into account in our 
sample size consideration. Alternative covariance structures for the repeated measures over time 
will be compared using Akaike’s Information Criteria (AIC). This model will be used to test 
specific hypotheses using contrast statements and to compare temporal changes over time 
between the intervention and control groups. Variables with baseline imbalances can be 
incorporated as additional fixed effects. We will also examine a clinically meaningful 30% 
improvement in PEG from baseline as a binary outcome (yes or no) at each follow-up time point 
using a logistic mixed effects model incorporating a random effect for class clustering. All 
analyses will be conducted in SAS version 9.4 with p<0.05 considered statistically significant 
unless otherwise specified. 
 
Hypothesis 2: patients in OPTIMUM will have significantly improved psychological function at 
completion of the program and 6- and 12-months later, as compared to PCP Usual Care. 
Analyses will mirror those described above using a mixed effects model with random effects for 
the clustering effect of intervention classes and repeated measures on individuals over time, with 
fixed effects for group, time and their interaction. Contrast statements will be used to compare 
changes from baseline to specific time points. All analyzes will be conducted in SAS version 9.4 
with p<0.05 considered statistically significant unless otherwise specified. 
 
Hypothesis 3: patients in OPTIMUM will be less likely to start and more likely to reduce or stop 
an opioid prescription for cLBP as compared to those in PCP Usual Care.  
We will examine opioid prescription for cLBP in two ways. First, we will examine the dose of 
opioids as morphine dose equivalent (continuous outcome) for those subjects with an opioid 
prescription at baseline.  The analytic approach will mirror the mixed models described for 
Hypothesis 1 to compare group doses over time and in relation to baseline.  Next we will use a 
binary outcome which is yes/no for opioid prescription (any) for each patient at each time point.  
Analytic methods will again mirror methods for Hypothesis 1 now using a logistic mixed effects 
model.    
 
Aim 2. To evaluate use of healthcare resources by patients.  
Hypothesis: patients in OPTIMUM will have fewer emergency department visits, fewer 
hospitalizations, fewer imaging (CT/MRI), and fewer procedures (injections, surgery) than PCP 
usual care.  
Healthcare utilization over 6- and 12-months (prescriptions of opioids, injections, surgery, 
CT/MRI, ED visits, hospitalizations) are mostly in the form of counts. We will fit a series of 
GEE models with each outcome as the dependent variable, a negative binomial distribution to 
account for over dispersion, a log link, exposed time period as an offset, intervention arm 
(OPTIMUM/Usual Care) as the independent factor of interest, and an exchangeable correlation 
structure for clustering. Alternative correlation structures will be examined via the QIC statistic. 
Intervention arm incident rate ratios and their significance will constitute the test of the 
hypothesis. 
      

 
Study Product Guidelines and Considerations 
32 of 57 
Version 1.1 
 
 
13 November 2020 
Aim 3. To evaluate PCP and practice site use of, satisfaction with, and integration of 
OPTIMUM.  
PCP satisfaction with the pain program will be summarized using descriptive statistics and 
histograms. We will also investigate if these measures are different depending on the 
demographic characteristics of the PCPs, such as gender, age, race, ethnicity, clinic location, and 
years since training, or the outcome of the patients using t-test, chi-square test, Pearson or 
Spearman correlation tests. Number of 8-week programs delivered at each clinic will also be 
summarized with descriptive statistics. Adoption of EHR tools and OPTIMUM after study 
completion will be described.  
 
Planned Analysis & Power Assessment  
The table below is of power calculations for the Optimum study using the PEG as the primary 
outcome.  An ICC estimate of 0.053 was used, which came from Dr. Lynn DeBar’s pragmatic 
clinical trial funded by NINDS which used the PEG.  The other assumptions are α= 0.05, SD of 
change = 2.5 and 20% attrition.  As the table illustrates, with a total sample size of 450, with an 
average of 10 subjects per cluster, we have close to 90% power to detect a 1-unit difference in 
the PEG between groups.  The table also illustrates calculations for a range of power and effect 
sizes. 
 
ICC = 0.053 
 
 
Obs 
power 
meandiff 
SD 
clustsize   
final_npergroup 
1 
0.80 
1.0 
2.5 
10   
184.625 
2 
0.85 
1.0 
2.5 
10   
210.473 
3 
0.90 
1.0 
2.5 
10   
245.551 
4 
0.80 
1.5 
2.5 
10   
83.081 
5 
0.85 
1.5 
2.5 
10   
94.159 
6 
0.90 
1.5 
2.5 
10   
110.775 
7 
0.80 
2.0 
2.5 
10   
48.003 
8 
0.85 
2.0 
2.5 
10   
55.388 
9 
0.90 
2.0 
2.5 
10   
62.773 
10 
0.80 
2.5 
2.5 
10   
31.386 
11 
0.85 
2.5 
2.5 
10   
35.079 
12 
0.90 
2.5 
2.5 
10   
42.464 
13 
0.80 
3.0 
2.5 
10   
22.155 

 
Study Product Guidelines and Considerations 
33 of 57 
Version 1.1 
 
 
13 November 2020 
Obs 
power 
meandiff 
SD 
clustsize   
final_npergroup 
14 
0.85 
3.0 
2.5 
10   
25.848 
15 
0.90 
3.0 
2.5 
10   
29.540 
 
 
 
Missing Data Considerations:   
 
We anticipate 20% attrition at the 8-week time point. We chose a higher attrition rate than in our 
previous work as we anticipate more attrition in the PCT as patients will not have the “high 
touch” of participants in the RCTs.5, 26, 28 Our sample size analyses have accounted for this 
amount of missing data. We will compare baseline characteristics between patients with the 
assessment immediately following the 8-week program to those without in order to assess 
potential bias in study completion. We will also try to obtain reasons for study drop out so that 
we can assess the missing data mechanism (missing completely at random (MCAR), missing at 
random (MAR), non-ignorable missingness). At a single time point, we will conduct sensitivity 
analyses assigning poor scores and good scores for missing values differentially by treatment 
assignment to evaluate the impact on our study results.  
 
The mixed models proposed for analysis are robust to missing data under MCAR and MAR 
missing data mechanisms.  If the amount missing data differs between treatment groups or 
appears to be non-ignorably missing, we will conduct sensitivity analyses with imputed data 
based on varying assumptions (ignorable vs. non-ignorable missingness). 
 
10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1 Data Collection 
Paperless Data Entry: A paperless data-entry system will be created in REDCap, a secure web 
application for building and managing online surveys and databases available to the PI (Morone) 
through the Boston University Clinical and Translational Science Institute. REDCap has proven 
to be a sophisticated yet easy-to-use data entry system that provides customizable templates for 
use in clinical trial research. All study participants will be assigned unique study identifiers that 
will appear on all data collection instruments, documents, and files used in the statistical analysis 
and manuscript preparation. REDCap allows for specific data quality measures to be 
implemented.  These include data verification and built-in data validation mechanisms such as 
logic and out of range data checks.  
10.2 Data Management  
EHR Data: Consenting and eligible participants will provide contact information containing 
protected health information (PHI) to each HCS’s research staff.  PHI will be stored separately 
from clinical data in a password protected electronic file and will be used to link and extract 
clinical data from each center’s EHR on a bi-weekly basis. Limited use datasets will be created 

 
Study Product Guidelines and Considerations 
34 of 57 
Version 1.1 
 
 
13 November 2020 
at each HCS and will contain a unique study identifier and clinical data including date of birth 
and visit dates; name, address, social security number and medical record number information 
will be removed. Limited use datasets will be transferred to the central data repository housed at 
Boston University Biostatistics and Epidemiology Data Analytics Center (BEDAC). The 
BEDAC is supported by the Boston University Medical Campus (BUMC) Information Systems 
and Technology group (IS&T). Data will reside on virtual machines stored inside the BUMC 
IS&T premium secure environment. Under IS&T, project database access is configured to 
require encrypted connections, databases are encrypted at rest (AES-256), and all actions to the 
database are logged. Database transfer will be electronically encrypted via IPsec tunnel or secure 
socket layering (SSL) encryption technology so that only the intended recipient can decode the 
data. Applications and databases will be protected by network firewalls that restrict access to 
designated users and hosts. Restriction and permissions to update the database and to share the 
database will be controlled by the BEDAC based on staff user role. The BEDAC data manager 
will develop data transfer specifications and work with each HCS to obtain data through the 
secure BEDAC portal. The limited use EHR data will be cleaned, aggregated and merged with 
study data for subsequent analysis. 
 
Missing data: We do not expect substantial missing data due to it being directly entered into the 
electronic data collection system, which we have used previously. This system has many 
safeguards such as prohibiting closure of a page if a question has not been answered or the 
answer is out of range. For instruments with several questions we will use the approach 
recommended by their authors for calculating total scores and composites when values for an 
item are missing. 
 
Compliance: We will estimate compliance by the number of sessions attended and estimate the  
Proportion of participants with various levels of compliance. We will also calculate the 
proportion of participants missing each session to describe the pattern of compliance. 
 
Dropout analyses: Participants informing us they no longer want to continue in the study will be 
considered dropouts, and we will look at when these events occur. Dropout rates will be 
calculated as proportions of participants randomized, and as a cumulative probability of 
remaining in the study, using survival analysis techniques such as the product-limit estimator. 
Unlike proportions, the latter statistics, which can be estimated at various times following 
randomization, take into account when dropouts occur. The information contained in these 
descriptive analyses may help us to devise strategies for keeping people in the study. 
10.3 Quality Assurance  
10.3.1 Training 
Protection of Human Subjects Training: All the members of the study team, investigators and 
staff, will complete the required training on protection of human subjects before engaging in any 
activities related to human subjects. According to the institution’s requirements, they will 
recertify if and when needed.  
 
Training of Mindfulness Instructors: We will train the Mindfulness instructors before starting 
the trial. We will explain the treatment protocol, appropriate adaptations for patient’s comfort 

 
Study Product Guidelines and Considerations 
35 of 57 
Version 1.1 
 
 
13 November 2020 
and emotional stresses and when to discontinue treatment. We will develop procedures for 
instructors so as to ask questions when issues surface and to communicate that information to 
instructors at other HCS sites. All sites have back-up instructors if needed. 
 
Training of Informed Consent Takers: Study personnel who will be taking informed consent 
from the study participants will be trained for the procedure.  
 
10.3.2 Quality Control Committee  
Principal Investigator (PI), Site Principal Investigators (s-PI), Co-Investigators (Co-I), 
Biostatistician and other study members as needed, will have a weekly or monthly (depends on 
study recruitment) to keep up with the day to day operations at each HCS site and assist if 
needed. They will discuss the progress of the trial, recruitment status and IRB concerns if 
applicable.  
10.3.3 Metrics 
We will develop automated reports that will include the number of participants screened, number 
enrolled, study assessments completed, participants missing assessments, and those participants 
with upcoming assessments. We will monitor intervention adherence with bimonthly reports. We 
will obtain data on age, gender, race and ethnicity to assure balanced randomization. For each 
timepoint we aim to achieve an 85% or higher follow-up rate. We anticipate other metrics and 
reports will be developed as we implement the pilot study. 
10.3.4 Protocol Deviations 
A protocol deviation will be defined as any lack of compliance with the study protocol, manual 
of operations or any other study related procedures that could increase the risk to the participant 
or affect the integrity of the trial. These deviations will be tracked down in a scheduled manner 
and reviewed at study team meetings. Additionally, they will be documented for IRB or NIH.  
10.3.5 Monitoring 
Study staff will all undergo training to obtain consent and administer measures. Fidelity will be 
monitored monthly for the MBSR instructors. Recruitment and retention will be monitored and 
reviewed at weekly meetings across sites. Safety will be monitored at monthly meetings. 
Additional monitoring procedures will be developed as required during the pilot trial.  
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 Institutional Review Board (IRB) Review  
The OPTIMUM study uses a single IRB (sIRB) which is the University of Pittsburgh. The 
protocol and the informed consent document (Appendix A) and any subsequent modifications 
will be reviewed and approved by the sIRB who is responsible for oversight of the study. The 
consent form and protocol are separate documents. 

 
Study Product Guidelines and Considerations 
36 of 57 
Version 1.1 
 
 
13 November 2020 
11.2 Informed Consent Forms 
A verbal consent  will be obtained from each participant. The consent form will describe the 
purpose of the study, the procedures to be followed, and the risks and benefits of participation. A 
copy will be emailed to each participant.  
11.3 Participant Confidentiality  
All precautions will be taken to ensure that participant’s privacy is respected. The collection of 
sensitive information related to participants is limited to the amount necessary to achieve the 
aims of the research, so that no unneeded sensitive information is being collected. Any screening 
that will be done in the clinic or research office will be done in a private room.  
 
All efforts will be taken to keep all the data collection electronic. Documents will be password 
protected and accessibility will be given only to the approved staff. All computer entry and 
networking programs will be done using PIDs only.  Minimum paper format data collection will 
be attempted. Any paper format data will be kept in locked file cabinets in locked offices and 
access to these files will be limited to study personnel. 
  
Identifying information will be coded and a key to decipher the code will exist, enabling linkage 
of the identifying information to the private information. If the participant withdraws from the 
study, any identifiable research or medical information recorded for or resulting from 
participation in the study before the date the participant formally withdraws consent may 
continue to be used and disclosed by the investigators for the purposes described in the study 
protocol. Research records including identifiable data will be securely stored indefinitely.  
11.4 Study Discontinuation  
The study may be discontinued at any time by the IRB, the NCCIH, the OHRP, or other 
government agencies as part of their duties to ensure that research participants are protected.  
12. COMMITTEES 
Collaboratory Core Working Group Members:  
 
Ethics/Regulatory: 
• Natalia Morone (PI) 
• Susan Gaylord (Site-PI) 
 
Biostatistics and Study Design, Health Care Systems Interactions: 
• Janice Weinberg (Co-I) 
 
Patient-Centered Outcomes: 
• Carol Greco (Site-Co-I) 
 
Electronic Health Records 
• Kathleen Mctigue (Site Co-PI) 
• Kim Faurot (Site Co-PI) 

 
Study Product Guidelines and Considerations 
37 of 57 
Version 1.1 
 
 
13 November 2020 
 
Health Care Systems 
• Natalia Morone (PI) 
13. PUBLICATION OF RESEARCH FINDINGS  
Publication of the results of this trial will be governed by the policies and procedures developed 
by the Collaboratory and Core Working Group Members. Any presentations, abstracts, or 
manuscripts will be made available for review by the NIH and the NCCIH prior to submission.  
14. REFERENCES  
 
1. 
Soni A. Back Probems: Use and Expenditures for the U.S. Adult Population, 2007. 
Rockville, MD: Agency for Healthcare Research and Quality;2010. 
2. 
Chou R, Deyo R, Devine B, et al. The Effectiveness and Risks of Long-Term Opioid 
Treatment of Chronic Pain. Evidence Report/Technology Assessment No. 218. (Prepared 
by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2012-
00014-I.) AHRQ Publication No. 14-E005-EF. Rockville, MD: Agency for Healthcare 
Research and Quality; September 2014.  
https://effectivehealthcare.ahrq.gov/topics/chronic-pain-opioid-treatment/research. Accessed 
2/2/2019.  
 3. 
Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid 
therapy for chronic pain: a systematic review for a National Institutes of Health Pathways 
to Prevention Workshop. Ann Intern Med. 2015;162(4):276-286.  
4. 
Deyo RA, Mirza SK, Turner JA, Martin BI. Overtreating chronic back pain: time to back 
off? Journal of the American Board of Family Medicine : JABFM. 2009;22(1):62-68. 
2729142. 
5. 
Morone NE, Greco CM, Moore CG, et al. A Mind-Body Program for Older Adults With 
Chronic Low Back Pain: A Randomized Clinical Trial. JAMA Intern Med. 
2016;176(3):329-337. NIHMSID766182  
6. 
Cherkin DC, Sherman KJ, Balderson BH, et al. Effect of Mindfulness-Based Stress 
Reduction vs Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional 
Limitations in Adults With Chronic Low Back Pain: A Randomized Clinical Trial. 
JAMA. 2016;315(12):1240-1249. PMC4914381. 
7. 
Qaseem A, Wilt TJ, McLean RM, Forciea MA, Clinical Guidelines Committee of the 
American College of P. Noninvasive Treatments for Acute, Subacute, and Chronic Low 
Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann 
Intern Med. 2017;166(7):514-530.  
8. 
Deyo RA, Mirza SK, Martin BI. Back pain prevalence and visit rates: estimates from 
U.S. national surveys, 2002. Spine (Phila Pa 1976). 2006;31(23):2724-2727.  
9. 
Centers for Disease Control and Prevention. National Ambulatory Medical Care Survey: 
2015. Table 11, page 13.  
https://www.cdc.gov/nchs/data/ahcd/namcs_summary/2015_namcs_web_tables.pdf. 
Accessed 2/2/2019.  
10. 
In: Relieving Pain in America: A Blueprint for Transforming Prevention, Care, 
Education, and Research. Washington (DC)2011. 

 
Study Product Guidelines and Considerations 
38 of 57 
Version 1.1 
 
 
13 November 2020 
 11. 
Hush JM, Cameron K, Mackey M. Patient satisfaction with musculoskeletal physical 
therapy care: a systematic review. Physical therapy. 2011;91(1):25-36.  
12. 
Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. BMJ. 2015;350:g6380.  
13. 
Krebs EE, Gravely A, Nugent S, et al. Effect of Opioid vs Nonopioid Medications on 
Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis 
Pain: The SPACE Randomized Clinical Trial. JAMA. 2018;319(9):872-882. 
PMC5885909. 
14. 
Skelly AC, Chou R, Dettori JR, et al. In: Noninvasive Nonpharmacological Treatment for 
Chronic Pain: A Systematic Review. Rockville (MD)2018. 
15. 
Gaynor CH, Vincent C, Safranek S, Illige M. FPIN's clinical inquiries. Group medical 
visits for the management of chronic pain. Am Fam Physician. 2007;76(11):1704-1705.  
16. 
Eisenstat SA, Ulman K, Siegel AL, Carlson K. Diabetes group visits: integrated medical 
care and behavioral support to improve diabetes care and outcomes from a primary care 
perspective. Curr Diab Rep. 2013;13(2):177-187.  
17. 
Jaber R, Braksmajer A, Trilling JS. Group visits: a qualitative review of current research. 
J Am Board Fam Med. 2006;19(3):276-290.  
18. 
Shaw S, Dresner D, Gardiner P, Barnett KG, Saper R. Integratvie Medicine Group Visits 
and Emergency Department Utilization. J Altern Complement Med. 2014;20(5):A67-
A68.  
19. 
Smith CE, Piamjariyakul U, Wick JA, et al. Multidisciplinary group clinic appointments: 
the Self-Management and Care of Heart Failure (SMAC-HF) trial. Circ Heart Fail. 
2014;7(6):888-894. PMC4241146. 
20. 
Housden LM, Wong ST. Using Group Medical Visits With Those Who Have Diabetes: 
Examining the Evidence. Curr Diab Rep. 2016;16(12):134.  
21. 
Levine MD, Ross TR, Balderson BH, Phelan EA. Implementing group medical visits for 
older adults at group health cooperative. J Am Geriatr Soc. 2010;58(1):168-172. 
PMC3005126. 
22. 
Gardiner P, Lestoquoy AS, Gergen-Barnett K, et al. Design of the integrative medical 
group visits randomized control trial for underserved patients with chronic pain and 
depression. Contemp Clin Trials. 2017;54:25-35.  
23. 
Dresner D, Gergen Barnett K, Resnick K, Laird LD, Gardiner P. Listening to Their 
Words: A Qualitative Analysis of Integrative Medicine Group Visits in an Urban 
Underserved Medical Setting. Pain Med. 2016 
24. 
Gardiner P, Dresner D, Barnett KG, Sadikova E, Saper R. Medical group visits: a 
feasibility study to manage patients with chronic pain in an underserved urban clinic. 
Glob Adv Health Med. 2014;3(4):20-26. PMC4104558. 
25. 
Clarke TC BL, Stussman BJ, Barnes PM, Nahin RL. Trends in the Use of 
Complementary Health Approaches Among Adults: United States, 2002-2012. National 
Health Statistics Reports;2015. 
26. 
Morone NE, Rollman BL, Moore CG, Li Q, Weiner DK. A mind-body program for older 
adults with chronic low back pain: results of a pilot study. Pain Med. 2009;10(8):1395-
1407. PMC2849802. 
27. 
Morone NE, Lynch CS, Greco CM, Tindle HA, Weiner DK. "I felt like a new person." 
the effects of mindfulness meditation on older adults with chronic pain: qualitative 
narrative analysis of diary entries. J Pain. 2008;9(9):841-848. PMC2569828. 

 
Study Product Guidelines and Considerations 
39 of 57 
Version 1.1 
 
 
13 November 2020 
28. 
Morone NE, Greco CM, Weiner DK. Mindfulness meditation for the treatment of chronic 
low back pain in older adults: a randomized controlled pilot study. Pain. 
2008;134(3):310-319. PMC2254507. 
29. 
Morone NE, Greco CM, Rollman BL, et al. The design and methods of the aging 
successfully with pain study. Contemp Clin Trials. 2012;33(2):417-425. PMC3268822. 
30. 
Luiggi-Hernandez JG, Woo J, Hamm M, Greco CM, Weiner DK, Morone NE. 
Mindfulness for Chronic Low Back Pain: A Qualitative Analysis. Pain Med. 
2018;19(11):2138-2145.  
31. 
Morone NE, Moore CG, Greco CM. Characteristics of Adults Who Used Mindfulness 
Meditation: United States, 2012. J Altern Complement Med. 2017;23(7):545-550.  
32. 
Taren AA, Gianaros PJ, Greco CM, et al. Mindfulness meditation training alters stress-
related amygdala resting state functional connectivity: a randomized controlled trial. Soc 
Cogn Affect Neurosci. 2015;10(12):1758-1768. PMC4666115. 
33. 
Simkin-Silverman LR, Conroy MB, Bhargava T, McTigue KM. Development of an 
online diabetes prevention lifestyle intervention coaching protocol for use in primary care 
practice. Diabetes Educ. 2011;37(2):263-268.  
34. 
McTigue KM, Conroy MB, Hess R, et al. Using the internet to translate an evidence-
based lifestyle intervention into practice. Telemed J E Health. 2009;15(9):851-858.  
35. 
McTigue KM, Conroy MB, Bigi L, Murphy C, McNeil M. Weight loss through living 
well: translating an effective lifestyle intervention into clinical practice. The Diabetes 
educator. 2009;35(2):199-204, 208.  
36. 
Smith KJ, Kuo S, Zgibor JC, et al. Cost effectiveness of an internet-delivered lifestyle 
intervention in primary care patients with high cardiovascular risk. Prev Med. 
2016;87:103-109.  
37. 
Arterburn D, Wellman R, Emiliano A, et al. Comparative Effectiveness and Safety of 
Bariatric Procedures for Weight Loss: A PCORnet Cohort Study. Ann Intern Med. 
2018;169(11):741-750.  
38. 
Toh S, Rasmussen-Torvik LJ, Harmata EE, et al. The National Patient-Centered Clinical 
Research Network (PCORnet) Bariatric Study Cohort: Rationale, Methods, and Baseline 
Characteristics. JMIR Res Protoc. 2017;6(12):e222. PMC5736875. 
39. 
Gaylord SA, Whitehead WE, Coble RS, et al. Mindfulness for irritable bowel syndrome: 
protocol development for a controlled clinical trial. BMC Complement Altern Med. 
2009;9:24. PMC2729728. 
40. 
Gaylord SA, Palsson OS, Garland EL, et al. Mindfulness training reduces the severity of 
irritable bowel syndrome in women: results of a randomized controlled trial. Am J 
Gastroenterol. 2011;106(9):1678-1688.  
41. 
Garland EL, Gaylord SA, Palsson O, Faurot K, Douglas Mann J, Whitehead WE. 
Therapeutic mechanisms of a mindfulness-based treatment for IBS: effects on visceral 
sensitivity, catastrophizing, and affective processing of pain sensations. J Behav Med. 
2012;35(6):591-602. PMC3883954. 
42. 
Bluth K, Gaylord S, Nguyen K, Bunevicius A, Girdler S. Mindfulness-based Stress 
Reduction as a Promising Intervention for Amelioration of Premenstrual Dysphoric 
Disorder Symptoms. Mindfulness (N Y). 2015;6(6):1292-1302. PMC4651211. 
43. 
Garland EL, Gaylord SA, Boettiger CA, Howard MO. Mindfulness training modifies 
cognitive, affective, and physiological mechanisms implicated in alcohol dependence: 

 
Study Product Guidelines and Considerations 
40 of 57 
Version 1.1 
 
 
13 November 2020 
results of a randomized controlled pilot trial. J Psychoactive Drugs. 2010;42(2):177-192. 
PMC2921532. 
44. 
Garland EL, Boettiger CA, Gaylord S, Chanon VW, Howard MO. Mindfulness is 
Inversely Associated with Alcohol Attentional Bias Among Recovering Alcohol-
Dependent Adults. Cognit Ther Res. 2012;36(5):441-450. PMC3532517. 
45. 
Jerger KK, Lundegard L, Piepmeier A, et al. Neural Mechanisms of Qigong Sensory 
Training Massage for Children With Autism Spectrum Disorder: A Feasibility Study. 
Glob Adv Health Med. 2018;7:2164956118769006. PMC5894902. 
46. 
Foley P, Steinberg D, Levine E, et al. Track: A randomized controlled trial of a digital 
health obesity treatment intervention for medically vulnerable primary care patients. 
Contemp Clin Trials. 2016;48:12-20. PMC4885789. 
47. 
Saper RB, Lemaster C, Delitto A, et al. Yoga, Physical Therapy, or Education for 
Chronic Low Back Pain: A Randomized Noninferiority Trial. Ann Intern Med. 
2017;167(2):85-94.  
48. 
Saper RB, Sherman KJ, Delitto A, et al. Yoga vs. physical therapy vs. education for 
chronic low back pain in predominantly minority populations: study protocol for a 
randomized controlled trial. Trials. 2014;15:67. PMC3944007. 
49. 
Saper RB, Boah AR, Keosaian J, Cerrada C, Weinberg J, Sherman KJ. Comparing Once- 
versus Twice-Weekly Yoga Classes for Chronic Low Back Pain in Predominantly Low 
Income Minorities: A Randomized Dosing Trial. Evid Based Complement Alternat Med. 
2013;2013:658030. PMC3710634. 
50. 
Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 
diabetes with lifestyle intervention or metformin. The New England journal of medicine. 
2002;346(6):393-403. 1370926. 
51. 
Deyo RA, Dworkin SF, Amtmann D, et al. Report of the NIH Task Force on research 
standards for chronic low back pain. Pain Med. 2014;15(8):1249-1267.  
52. 
Kabat-Zinn J. Mindfulness-based interventions in context: Past, present, and future. 
Clinical Psychology: Science & Practice. 2003;10(2):144-156.  
53. 
Goldsmith ES, Taylor BC, Greer N, et al. Focused Evidence Review: Psychometric 
Properties of Patient-Reported Outcome Measures for Chronic Musculoskeletal Pain. J 
Gen Intern Med. 2018;33(Suppl 1):61-70. PMC5902346. 
54. 
Cella D, Riley W, Stone A, et al. The Patient-Reported Outcomes Measurement 
Information System (PROMIS) developed and tested its first wave of adult self-reported 
health outcome item banks: 2005-2008. J Clin Epidemiol. 2010;63(11):1179-1194. 
PMC2965562. 
55. 
Meltzer EC, Rybin D, Saitz R, et al. Identifying prescription opioid use disorder in 
primary care: diagnostic characteristics of the Current Opioid Misuse Measure (COMM). 
Pain. 2011;152(2):397-402. PMC3027065. 
56. 
Fals-Stewart W, O'Farrell TJ, Freitas TT, McFarlin SK, Rutigliano P. The timeline 
followback reports of psychoactive substance use by drug-abusing patients: psychometric 
properties. J Consult Clin Psychol. 2000;68(1):134-144.  
57. 
McTigue KM, Bhargava T, Bryce CL, et al. Patient perspectives on the integration of an 
intensive online behavioral weight loss intervention into primary care. Patient Educ 
Couns. 2011;83(2):261-264.  
58. 
McTigue KM, Conroy MB. Use of the internet in the treatment of obesity and prevention 
of type 2 diabetes in primary care. Proc Nutr Soc. 2013;72(1):98-108.  

 
Study Product Guidelines and Considerations 
41 of 57 
Version 1.1 
 
 
13 November 2020 
59. 
Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic 
Pain - United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49.  
60. 
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying 
prognostic comorbidity in longitudinal studies: development and validation. J Chronic 
Dis. 1987;40(5):373-383.  
61. 
Hanks G, Cherny N. Opioid analgesic therapy. In: Doyle D, Hanks G, MacDonald N, 
eds. Oxford Textbook of Palliative Medicine. Second ed. Oxford: Oxford University 
Press; 1998:331-355. 
62. 
Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-
2 tool: designing trials that are fit for purpose. BMJ. 2015;350:h2147.  
63. 
Donner A, Klar N. Design and Analysis of Cluster Randomization Trials in Health 
Research. London, U.K.: Arnold Publishing Company; 2000. 
 
 
 
 
 
 
15. SUPPLEMENTS/APPENDICES 
 
Appendix A: Informed Consent Form Updated 
 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
Title: Group-based mindfulness for patients with chronic low back pain  
in the primary care setting versus usual care 
 
Principal Investigator: 
 
<Insert local Principal Investigator here> 
 
Co-Investigators: 
<Insert local Co-Is here> 
 
 
Source of Support: National Institutes of Health, National Center for Complementary and 
Integrative Health 
 
 
 
CONCISE SUMMARY 
The purpose of this research study is to determine whether a group pain management program   
modeled on Mindfulness-Based Stress Reduction can improve pain and function for persons with 
chronic low back pain as compared to persons receiving usual care by their primary care 
providers. All persons who are eligible will complete surveys about pain, function, sleep, pain 
medicine use, tobacco, alcohol and substance use, mood and anxiety symptoms, experience with 
telehealth and quality of life. The surveys will take up to an hour to complete. Once the surveys 
are complete, all persons will be randomized to the group-based pain management program or to 

 
Study Product Guidelines and Considerations 
42 of 57 
Version 1.1 
 
 
13 November 2020 
usual care. If you are randomized to the group pain management program you will meet  for 8 
weekly group sessions via ZOOM. Each session will last for 120 minutes. The first 30 minutes 
will be a standard of care telehealth video visit with a primary care provider and the last 90 
minutes will be the  video group pain management program. Regardless of which group you are 
assigned to, you will be emailed and asked to complete  follow-up surveys that will occur at 8 
weeks, 6 months and 12 months. You will also be asked to complete a monthly survey about any 
visits to the hospital or your primary care provider, and you will be called monthly to review 
your pain medications. If you are randomized to the usual care group you will not participate in 
the pain management program, but you will receive the surveys to complete and the monthly 
phone call. The total time for your participation in this study will be 12 months.   
 
The greatest risks of this study if you are randomized to either group is loss of confidentiality. 
The greatest risks of this study if you are randomized to the 8-week pain management program 
include the possibility of discomfort when sitting in a chair or doing mindfulness meditation 
which includes mindful chair exercises, emotional discomfort or distress arising during 
meditation related to increased awareness of negative emotions, thoughts or physical sensations.  
 
ClinicalTrials.gov 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
 
What are some general things you should know about research studies? 
You are being asked to take part in a research study.  To join the study is voluntary. 
You may choose not to participate, or you may withdraw your consent to be in the study, for any 
reason, without penalty. 
 
Research studies are designed to obtain new knowledge. This new information may help people 
in the future.   You may not receive any direct benefit from being in the research study. There 
also may be risks to being in research studies. Deciding not to be in the study or leaving the 
study before it is done will not affect your relationship with the researcher, your health care 
provider, or the <Insert local language here>. If you are a patient with an illness, you do not have 
to be in the research study in order to receive health care. 
 
Details about this study are discussed below.  It is important that you understand this information 
so that you can make an informed choice about being in this research study.  
 
You will be given a copy of this consent form or you will be mailed or emailed a copy of the 
consent form.  You should ask the researchers named above, or staff members who may assist 
them, any questions you have about this study at any time. 
 
Why is this research being done? 
The purpose of conducting this research is to determine if an 8-week mind-body program known 
as Mindfulness-Based Stress Reduction helps adults with chronic low back pain when offered in 
their doctor’s office in a telehealth video visit as compared to usual primary care. 
 

 
Study Product Guidelines and Considerations 
43 of 57 
Version 1.1 
 
 
13 November 2020 
Who is being asked to take part in this research study? 
You are being invited to take part in this research study because you are an English-speaking 
adult who is at least 18 years old and you have chronic low back pain. People invited into this 
study can be either male or female. You will be one of approximately 150 people to be asked to 
participate at this location. At all sites up to 450 volunteers will take part in this study.  
 
What procedures will be performed for research purposes? 
If you decide to take part in this research study, you will undergo the following research 
procedures: 
 
Baseline Testing: 
If you decide to join the study, you will undergo the following procedures that are not part of 
your standard medical care. They will take about 60 minutes of your time and will happen over 
the phone, mailed to you with a self-addressed return envelope, or can be completed online. If 
you complete the questionnaires online you will be sent a link that only you can access.  
You will be asked a series of questions about your mood, pain levels, sleep, health, activity, 
tobacco, alcohol, substance use, experience with telehealth and functional abilities. You will also 
be asked questions about demographic factors like age, gender, and ethnicity, as well as 
questions about medications that you take and healthcare that you receive.  
 
Experimental Procedures 
After you complete the baseline testing, you will undergo the following experimental 
procedures: 
 
Randomization: 
You will be assigned to one of the two options by randomization (like the flip of a coin), and you 
will have a 50% chance of being randomized to one of these options. One option will be usual 
care which means you will not participate in the group pain management program.  
 
The other option will be the group pain management program modeled on the Mindfulness-
Based Stress Reduction Program. The program meets weekly for 8 weeks via ZOOM for a total 
of 2 hours each week. 
 
During the first week you will be introduced to the principles and practice of mindfulness 
meditation. The home  practice assignment of daily meditation (six of seven days/week) will be 
reviewed. Support materials of guided meditation and a group manual will be provided. The 
sessions will occur in a videoconferencing format using HIPPA-compliant ZOOM.  
 
Follow-up Testing for Everyone: 
 
8 Week Follow-Up:  
After about 8-weeks from completing the Baseline surveys you will again be asked to answer the 
questions described under Baseline Testing above. You will also be asked about your satisfaction 
with the program if you were randomized to the pain management program. This will take on 
average 60 minutes, and you will be emailed a unique link to complete the surveys. The surveys  

 
Study Product Guidelines and Considerations 
44 of 57 
Version 1.1 
 
 
13 November 2020 
can also be completed over the telephone, over Zoom, or mailed to you with a self-addressed 
stamped envelope to return the questionnaires. 
 
Monthly Assessments: 
You will receive monthly phone calls or meet over Zoom to review your pain medications. You 
will also be emailed one survey to complete each month about any visits you made to a doctor, 
ER, hospital, or other healthcare facility related to your low back pain. 
 
6-Month and 12-Months Follow-Up: 
You will be asked to answer the questions described under Baseline Testing above after 6 
months and 12 months.  
 
Interview: 
 
If you are randomized to the group pain management program and when you complete the 8-
week program you will be invited to participate in an interview. The purpose of the interview is 
to collect personal accounts of the experience of learning mindfulness and how it has affected 
your life as well as your experience with the videoconferencing format.  
 
In order to ensure that we do not miss any of your comments, we ask permission to audio record 
your interview using ZOOM. This audio recording will only be listened to by members of the 
research team and will be securely stored on password protected servers. We will transcribe the 
recording without your name or any identifiers, but rather with a Study ID. Your identity will 
never be associated with your comments in any reports about this study. If you do not wish to be 
recorded, please let us know, and we will take notes only. 
 
What are the possible risks, side effects, and discomforts of this research study? 
There is less than minimal risk and discomfort associated with this research.  
 
For all participants there is a risk of breach of confidentiality. The risk will be minimized by the 
use of study IDs in place of participant names on all study related materials. 
 
If you are randomized to the 8-week group pain management program you may also have the 
following possible risks: 
• You may experience increased discomfort in your back from sitting on a chair during 
sitting meditation. However, you will be taught how to mindfully change your posture if 
worsened back pain should occur.  
 
• You may experience increased discomfort in your back from doing any of the 
mindfulness meditations like the mindfulness chair exercises. You will also be taught 
how to mindfully change your posture if worsened back pain should occur. 
 
• Emotional discomfort or distress may arise during meditation related to increased 
awareness of negative emotions, thoughts, or physical sensations. These symptoms are 
usually transient.  You can avoid any practices that lead to more than transient 
discomfort.    

 
Study Product Guidelines and Considerations 
45 of 57 
Version 1.1 
 
 
13 November 2020 
 
• 
For the group pain management program we will use Zoom, a videoconferencing 
program that uses end-to-end encryption. Although every reasonable effort has been 
taken, confidentiality during Internet communication activities cannot be guaranteed and 
it is possible that additional information beyond that collected for research purposes may 
be captured and used by others not associated with this study. Moreover, the use of video 
allows other participants to see and hear anything that occurs in your background 
surroundings while the camera and microphone are on during the sessions. We will 
provide a headset to you so that others who are in the room with you cannot hear what is 
being said by others on Zoom. 
 
What are the possible benefits from taking part in this research study?  
The potential benefit of your participation in the study is that you will learn techniques and 
information that may reduce your pain. There is no guarantee that you will receive such a 
benefit, but knowledge will be gained that may help others. 
 
If you agree to take part in this research study, will you be told of any new risks that may be 
found during the course of the study? 
You will be promptly notified if any new information develops during the conduct of this 
research study which may cause you to change your mind about continuing to participate. 
 
Will it cost you anything to be in this study? 
Neither you, nor your insurance provider will be charged for the costs of conducting procedures 
specifically being performed for research purposes. The procedures being performed specifically 
for research are the completion of surveys, the MSBR sessions, the interview when the program 
is finished and a medical record review.  
 
<INCLUDE BELOW LANGUAGE ONLY IF IT APPLIES TO YOUR SITE>However, you or 
your insurance provider will be charged for any procedures performed as part of your standard 
medical care (care you would receive even if you were not participating in this research study), 
in the usual manner. For this research study, the telehealth video group-based medical visits that 
will occur with a physician or primary care provider, prior to the MSBR sessions, are being 
completed for standard of care purposes. You may also need to pay for parking or public 
transportation. You may also need to pay a co-pay for your standard of care medical visit. You 
will not be charged for any other study procedures. 
 
Will you be paid if you take part in this research study? 
<INCLUDE BELOW LANGUAGE FOR WHAT APPLIES TO YOUR SITE> 
You will be paid <INSERT LOCAL AMOUNT TO BE PAID FOR EACH SURVEY> after the 
completion of surveys at baseline, 8 weeks, 6 months, 12 months, and monthly surveys.  This 
means if you complete all the surveys you will receive a total of <INSERT LOCAL AMOUNT 
TO BE PAID FOR COMPLETING  all the SURVEYS>.  You will also be paid <INSERT 
LOCAL AMOUNT TO BE PAID FOR THE INTERVIEW> if you complete the interview. If 
you are randomized to the pain management program and you do not have a computer, laptop, 
smart phone, or tablet then one will be provided for you. This device may be returned at the end 
of your participation. 

 
Study Product Guidelines and Considerations 
46 of 57 
Version 1.1 
 
 
13 November 2020 
 
 
<INSERT LOCAL LANGUAGE - If your institution has any additional local language that is 
needed regarding how payments are provided (cash, debit card) or if personal identifiers such as 
SSN need to be collected to process payments at your institution, insert it here>  
 
Who will pay if you are injured as a result of taking part in this research study? 
 
<Insert local compensation for injury language here> 
 
What if you are a <Insert local language here> student? <If your institution does not have an 
academic center attached to it, this entire section can be deleted> 
You may choose not to be in the study or to stop being in the study before it is over at any 
time.  This will not affect your class standing or grades at the <Insert local language here>.  You 
will not be offered or receive any special consideration if you take part in this research. 
 
What if you are a <Insert local language here> employee? 
Taking part in this research is not a part of your University duties, and refusing will not affect 
your job.  You will not be offered or receive any special job-related consideration if you take part 
in this research. 
 
How will information collected about me be kept confidential? 
We must use information that shows your identity to do this research. Information already 
collected about you will remain in the study record even if you later withdraw.  
 
We will store your information in ways we think are secure. We will store paper files in locked 
filing cabinets. We will store electronic files in computer systems with password protection and 
encryption. However, we cannot guarantee complete confidentiality. 
 
With your permission, we will use texts to send you information like appointment reminders or 
requests to complete study activities. Texting is unencrypted and therefore there is a chance this 
information can be intercepted. However, we will only text information that is not sensitive. If 
you do not wish to be texted, please let us know.  
 
As the Funder of this project, the National Institutes of Health requires that the researchers share 
all of the data we collect in this research study into a National Institutes of Health data repository 
called HEAL (Helping to End Addiction Long-term). The purpose of this data repository is for 
people who do research in the future to use the data to answer more research questions. All of 
your personal identifiers will be removed from the data before being placed in the repository.   
 
This study is covered by a Certificate of Confidentiality (CoC) from the National Institutes of 
Health. All studies funded by the National Institutes of Health that involve identifiable 
information are covered by a CoC. The CoC provides how we can share research information. 
Because we have a CoC, we cannot give out research information that may identify you to 
anyone that is not involved in the research except as we describe below. Even if someone tries to 

 
Study Product Guidelines and Considerations 
47 of 57 
Version 1.1 
 
 
13 November 2020 
get your information in connection with a legal proceeding, we cannot give it to them. The CoC 
does not prevent you from sharing your own research information.  
 
Will this research study involve the use of your medical record information? 
Yes, the Researchers involved in this study are requesting your authorization or permission to 
review your medical records.   
 
Who is requesting the Protected Health Information (PHI) for research? 
The researchers involved in this study are also requesting your authorization or permission to 
review your medical records. 
 
Why is this information needed? 
To determine whether you meet the conditions for participation in this study, to compare your 
earlier test results to the findings from this study, and if possible, to use your previous exam 
results in place of, or in addition to, some of the exams needed for this study. 
 
What will be disclosed? 
We will obtain the following information: your diagnoses, age, past medical history, 
medications, past surgeries, social history, diagnostic procedures including CT scans and MRIs, 
emergency department visits, surgeries, hospitalizations, urgent care visits, visits to your primary 
care clinic, physical therapy visits, injections for your back, and results of any blood tests. 
 
Will research data be placed in the medical record?  
No research data will be placed in the medical record. 
 
How long will this information be made available to the researchers? 
This identifiable medical record information will be made available to members of the research 
team for an indefinite period of time. 
 
Who (other than the investigators) will receive the PHI, and how will they use it? 
Your medical information, as well as information obtained during this research study, may be 
shared with other groups, possibly including authorized officials from the Food and Drug 
Administration, the National Center for Complementary and Integrative Health, the National 
Institutes of Health and the <INSERT name of local office that handles post-approval monitoring 
at your institution>, for the purpose of monitoring this study. Authorized representatives of 
<INSERT LOCAL LANGUAGE HERE> or affiliated health care providers may also have 
access to this information to provide service and addressing billing and operational issues. 
 
Your research data may also be shared with other research investigators who are not involved in 
this particular research study. These secondary research investigators will use the data to conduct 
future research studies. However, all identifiers will be stripped from your data before it’s 
provided to other researchers. So, your identity will not be shared with these secondary 
investigators. 
 
What is the potential risk that PHI will be re-disclosed by a recipient? 

 
Study Product Guidelines and Considerations 
48 of 57 
Version 1.1 
 
 
13 November 2020 
We will protect your privacy and the confidentiality of your records, as described in this 
document, but cannot guarantee the confidentiality of your research records, including 
information obtained from your medical records, once your personal information is disclosed to 
others outside <INSERT LOCAL LANGUAGE HERE> or the University. 
 
How long will this authorization be valid? 
This authorization is valid for an indefinite period of time. 
 
Do I have the right to revoke authorization, and how do I revoke it?  
You can always withdraw your authorization to allow the research team to review your medical 
records by contacting the investigator listed on the first page and making the request in writing. 
 
What are the implications of revocation of authorization? 
If you do so, you will no longer be permitted to participate in this study. Any information 
obtained from you up to that point will continue to be used by the research team. 
 
What are the implications of not providing consent to participate in the study? 
If you do not provide consent you cannot participate in the study. 
 
If you agree to take part in this research study, can you be removed from the study without 
your consent? 
The investigators have the right to stop your participation at any time. This could be because you 
have had an unexpected reaction, or have failed to follow instructions, or because the entire 
study has been stopped. 
 
VOLUNTARY CONSENT: 
All of the above has been explained to me and all of my current questions have been answered. I 
understand that I am encouraged to ask questions about any aspect of this research study during 
the course of this study, and that such future questions will be answered by the researchers listed 
on the first page of this form. 
 
If you have any questions about your rights as a research subject or wish to talk to someone other 
than the research team, please call the <Insert local language here> Human Subjects Protection 
Advocate toll-free at  <Insert local language here>. 
 
Participant’s Agreement: 
I have read the information provided above.  I have asked all the questions I have at this time. I 
provide my voluntary consent to participate in this research study and authorization for my 
medical records to be accessed and recorded for research purposes.  
 
 
 
 
 
 
CERTIFICATION OF INFORMED CONSENT 
 

 
Study Product Guidelines and Considerations 
49 of 57 
Version 1.1 
 
 
13 November 2020 
I certify that I have explained the nature and purpose of this research study to the above-named 
individual(s), and I have discussed the potential benefits and possible risks of study participation. 
Any questions the individual(s) have about this study have been answered, and we will always be 
available to address future questions, concerns or complaints as they arise. I further certify that 
no research component of this protocol was begun until after informed consent was provided. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix B: Important Medical Event Form 
 
 
Participant ID _________________________________    Form Completion Date __________ 
 
Form Completed by ______________________________ Group: _______ Arm:  O1  O2  O3 
 
DO NOT ask the questions below directly (except for #5). Allow the participant to describe the 
event and then ask for clarification, if needed. Fill out a separate form for each event.  
 
1. Important medical event occurred  [  ] Yes  [  ]  No        Date of the event ____________ 
 
2. Nature of the event: 
[  ] Hospitalization 
[  ] Emergency Room visit 
[  ] Acute Care Visit 
[  ] Pregnancy 
[  ] Outpatient Procedure 

 
Study Product Guidelines and Considerations 
50 of 57 
Version 1.1 
 
 
13 November 2020 
[  ] Other, Specify __________________________ 
 
3. Description of the event and its follow up (include details in the space below): 
[  ] Injury    [  ] Illness    [  ] Surgery    [  ] New Medication    [  ] Other (specify) 
 
 
4. Ask the participant: “Was this event related to your participation in the OPTIMUM 
study?”  
[  ] Yes    [  ] No 
 
5. Severity of the event 
[  ] Mild: required no or minimal treatment; able to carry out normal activities 
[  ] Moderate: resolved with treatment; normal activities conducted with some limitations 
[  ] Severe: required extensive medical attention; unable to carry out normal activities 
[  ] Very severe: life-threatening, disabling, fatal 
 
6. Action taken by study staff: 
[  ] Instructed participant to contact PCP                     [  ] Study contacted PCP 
[  ] Instructed participant to follow MD orders            [  ] Study contacted IRB and DSMB 
 
NOTE: This form should be immediately shared with the study Project Coordinator or PI. 
 
 
 
 
 
 
 
Appendix C: Screening Questions  
 
Obtain verbal consent to continue with these questions before proceeding. 
 
_____ Check here when you have obtained that consent.  DO NOT continue without verbal consent. 
 
 
                           
Today’s Date:  
Time:   
 
Date of Birth:              
 
Age: 
Participants MUST be at least 18 years old. If not STOP AND 
EXCLUDE 
 
Gender: ○ MALE   
○ FEMALE        ○ Unknown        ○ Other, Specify _________________ 
____________________________________________________________________________________
___ 
 
1a. Do you have low back pain or discomfort right now?   ○ Yes ○ No     If yes go to # 2. If no go to # 1b.     
 
1b. Have you ever had low back pain or discomfort?        ○ Yes ○ No     If yes go to # 2. If no STOP AND 
EXCLUDE 
 

 
Study Product Guidelines and Considerations 
51 of 57 
Version 1.1 
 
 
13 November 2020 
2. How long has low back pain been an ongoing problem for you? 
 
○ Less than one month   ○ 1-3 Months         ○ 3-6 months 
     If 1-3 months or less STOP AND 
EXCLUDE 
○ 6 months-1 year   ○ 1-5 years         ○ More than 5 years 
 
 
3. How often has low back pain been an ongoing problem for you over the past 6 months? 
 
○ Every day or nearly every day in the past 6 months  
 
○ At least half the days in the last 6 months  
 
 
 
 
○ Less than half the days in the past 6 months 
 
If less than half the days in the past 6 months STOP AND EXCLUDE 
 
4. a) What number best describes your pain on average in the past week?  
__0 
  __1 
__2 
__3 
__4 
__5 
__6 
__7 
__8 
__9 
__10  
No Pain 
 
 
 
 
 
 
 
 
Pain as bad as you can 
imagine 
 
b) What number best describes how, during the past week, pain has interfered with your enjoyment of 
life? 
__0 
   __1 
__2 
__3 
__4 
__5 
__6 
__7 
__8 
__9 
__10  
Does not 
 
 
 
 
 
 
 
 
Completely Interferes 
Interfere 
 
c) What number best describes how, during the past week, pain has interfered with your general activity? 
__0 
   __1 
__2 
__3 
__4 
__5 
__6 
__7 
__8 
__9 
__10 
Does not 
 
 
 
 
 
 
 
 
Completely Interferes 
Interfere 
 
If the average of the three questions is < 3 STOP AND EXCLUDE 
 
5.  Do you practice mindfulness meditation at least once a week? 
○ Yes   
○ No 
     If Yes, STOP AND EXCLUDE 
 
6.  Have you had any unintentional weight loss?   
 
 
 
○ Yes   
○ No 
How much weight loss?  ____  If ≥ 10 lbs STOP and EXCLUDE 
 
7.  Do you currently have an unexplained fever?   
 
 
 
○ Yes   
○ No 
     If Yes, STOP AND EXCLUDE 
 
8.  Do you have cancer?  If Yes, go to 8a 
 
 
 
 
○ Yes   
○ No 
 
8a.  Are you currently being treated for cancer?    
 
 
 
○ Yes   
○ No  
     If Yes, STOP AND EXCLUDE 
 
9. Has there been a recent unexplained worsening of your pain?   
 
○ Yes   
○ No  
     If Yes, STOP AND EXCLUDE 
 
10.  Is your back pain caused by an injury that occurred within the last 3 months? ○ Yes   
○ No  
     If Yes, STOP AND EXCLUDE 
 
11. Are you pregnant or have plans to become pregnant in the next 3 months? 
○ Yes   
○ No  

 
Study Product Guidelines and Considerations 
52 of 57 
Version 1.1 
 
 
13 November 2020 
     If Yes, STOP AND EXCLUDE 
 
 
Eligible for study?  ○ Yes ○ No 
 
If eligible, interested in participating?     ○ Yes       ○ No      ○ Uncertain/undecided      ○ Declined 
 
If declined, why did he/she decline? 
__________________________________________________________ 
 
 
COMMENTS (please print, enter only essential information): 
 
Contact Information: 
 
Name: _____________________________________________________________________________ 
 
Address: ___________________________________________________________________________ 
 
Phone Number: ______________________________________________________________________ 
 
E-mail Address: ______________________________________________________________________ 
 
 

 
Study Product Guidelines and Considerations 
53 of 57 
Version 1.1 
 
 
13 November 2020 
Appendix D: Timeline of the study updated. 
OPTIMUM – PCT Schedule 
UH3 Phase: Total 450 study participants 
Short Summary: 
TIMUM + PCP Usual Care 
(n=225) 
PCP Usual Care 
(n=225) 
8 Week Mindfulness 
Program 
6 months 
Assessment Date 
12 mon
Assessmen
  
Pittsburgh 
North 
Carolina 
Boston 
Pittsburgh 
North 
Carolina 
1 
Cohort 1 
Cohort 1 
Cohort 1 
Cohort 1 
Cohort 1 
Mar 2021 to Apr 2021 
August 2021 
February
2 
Cohort 2 
Cohort 2 
Cohort 2 
Cohort 2 
Cohort 2 
Jun 2021 to Jul 2021 
November 2021 
May 20
3 
Cohort 3 
Cohort 3 
Cohort 3  
Cohort 3 
Cohort 3 
Late Aug 2021 to Sep 
2021 
February 2022 
August 2
4 
Cohort 4 
Cohort 4 
Cohort 4 
Cohort 4 
Cohort 4 
Nov 2021 to early Jan 
2022 
April 2022 
October 
5 
Cohort 5 
Cohort 5 
Cohort 5 
Cohort 5  
Cohort 5 
Feb 2022 to Mar 2022 
July 2022 
January 
6 
Cohort 6 
Cohort 6 
Cohort 6 
Cohort 6  
Cohort 6 
Late Apr 2022 to Early 
Jun 2022 
September 2022 
March 2
7 
Cohort 7 
Cohort 7 
Cohort 7 
Cohort 7 
Cohort 7 
Jul 2022 to Aug 2022 
December 2022 
June 20
8 
Cohort 8 
Cohort 8 
Cohort 8 
Cohort 8 
Cohort 8 
Late Sep 2022 to Early 
Nov 2022 
February 2023 
August 2
9 
Cohort 9 
Cohort 9 
Cohort 9 
Cohort 9 
Cohort 9 
Dec 2022 to Jan 2023 
May 2023 
Novembe
10 
Cohort 10 
Cohort 10 
Cohort 10 
Cohort 10  
Cohort 10 
Mar 2022 to Apr 2023 
August 2023 
February
 
 
Enrollment Status 
Dates 
Cohorts  
25% Enrollment Complete 
May 2021 
Cohort 1 – Cohort 3  
50% Enrollment Complete 
February 2022 
Cohort 4 – Cohort 5 

 
Study Product Guidelines and Considerations 
54 of 57 
Version 1.1 
 
 
13 November 2020 
75% Enrollment Complete 
August 2022 
Cohort 6 – Cohort 8 
100% Enrollment Complete 
February 2023 
Cohort 9 – Cohort 10 
 
 
 
Detailed Schedule: 
Baseline 
Assessmen
T1) 
Week 1 
Week 2 
Week 3  
Week 4 
Week 5  
Week 6 
Week 7  
Week 8 
8 Weeks 
Post 
Program 
Assessment 
(T2) 
Assessment
at 6 months
(T3) 
ticipants (3 = OPTIMUM + PCP Usual Care, 2 = PCP Usual Care)  
December 
020-
ebruary 
021 
First week 
of March 
2021 
Second 
week of 
March 
2021 
Third 
week of 
March 
2021 
Fourth 
week of 
March 
2021 
Fifth week 
of March 
2021 
First week 
of April 
2021 
Second 
week of 
April 2021 
Third 
week of 
April 2021 
Fourth week 
of April 
2021 
August 2021
ticipants (24 = OPTIMUM + PCP Usual Care, 24 = PCP Usual Care)  
April-May 
021 
First week 
of June 
2021 
Second 
week of 
June 2021 
Third 
week of 
June 2021 
Fourth 
week of 
June 2021 
Fifth week 
of June 
2021 
 
 
 
First week 
of July 
2021 
Second 
week of 
July 2021 
Third 
week of 
July 2021 
Fourth week 
of July 2021 
November 
2021 
ticipants (24 = OPTIMUM + PCP Usual Care, 24 = PCP Usual Care) 
Complete 

 
Study Product Guidelines and Considerations 
55 of 57 
Version 1.1 
 
 
13 November 2020 
uly-August 
021 
Third 
week of 
August 
2021 
Fourth 
week of 
August 
2021 
First week 
of 
Septembe
r 2021 
Second 
week of 
Septembe
r 2021 
Third 
week of 
Septembe
r 2021 
Second 
week of 
October 
2021 
Fourth 
week of 
Septembe
r 2021 
Fifth week 
of 
Septembe
r 2021 
First week 
of October 
2021 
February 
2022 
ticipants (24 = OPTIMUM + PCP Usual Care, 24 = PCP Usual Care) 
eptember-
October 
021 
First week 
of 
Novembe
r 2021 
Second 
week of 
Novembe
r 2021 
Third 
week of 
Novembe
r 2021 
Fourth 
week of 
Novembe
r 2021 
First week 
of 
December 
2021 
Second 
week of 
December 
2021 
Third 
week of 
December 
2021 
Fourth 
week of 
December 
2021 
First week 
of January 
2023  
April 2022 
ticipants (24 = OPTIMUM + PCP Usual Care, 24 = PCP Usual Care) 
Complete 
anuary-
ebruary 
022 
First week 
of 
February 
2022 
Second 
week of 
February 
2022 
Third 
week of 
February2
022 
Fourth 
week of 
February 
2022 
First week 
of March 
2022 
Second 
week of 
March 
2022 
Third 
week of 
March 
2022 
Fourth 
week of 
March 
2022 
Fifth week 
of March 
2022 
July 2022 
ticipants (24 = OPTIMUM + PCP Usual Care, 24 = PCP Usual Care)  
March-
April 2022 
Fourth 
week of 
April 2022 
First week 
of May 
2022 
Second 
week of 
May 2022 
Third 
week of 
May 2022 
Fourth 
week of 
May 2022 
Fifth week 
of May 
2022 
First week 
of June 
2022 
Second 
week of 
June 2022 
Third week 
of June 
2022 
September 
2022 
ticipants (24 = OPTIMUM + PCP Usual Care, 24 = PCP Usual Care) 

 
Study Product Guidelines and Considerations 
56 of 57 
Version 1.1 
 
 
13 November 2020 
May-June 
022 
First week 
of July 
2022 
Second 
week of 
July 2022 
Third 
week of 
July 2022 
Fourth 
week of 
July 2022 
First week 
of August 
2022 
Second 
week of 
August 
2022 
Third 
week of 
August 
2022 
Fourth 
week of 
August 
2022 
Fifth week 
of August 
2022 
December 
2022 
ticipants (24 = OPTIMUM + PCP Usual Care, 24 = PCP Usual Care) 
Complete 
uly-August 
022 
Second 
week of 
Septembe
r 2022 
Third 
week of 
Septembe
r 2022 
Fourth 
week of 
Septembe
r 2022 
First week 
of 
October 
2022 
Second 
week of 
October 
2022 
Third 
week of 
October 
2022 
Fourth 
week of 
October 
2022 
First week 
of 
Novembe
r 2022 
Second 
week of 
November 
2022 
February 
2023 
ticipants (24 = OPTIMUM + PCP Usual Care, 24 = PCP Usual Care) 
October-
November 
022 
First week 
of 
December 
2022 
Second 
week of 
December 
2022 
Third 
week of 
December 
2022 
First week 
of January 
2023 
Second 
week of 
January 
2023 
Third 
week of 
January 
2023 
Fourth 
week of 
January 
2023 
Fifth week 
of January 
2023 
First week 
of February 
2023 
May 2023 
rticipants (26 = OPTIMUM + PCP Usual Care, 25 = PCP Usual Care)  
t Complete 
anuary-
ebruary 
023 
First week 
of March 
2023 
Second 
week of 
March 
2023 
Third 
week of 
March 
2023 
Fourth 
week of 
March 
2023 
First week 
of April 
2023 
Second 
week of 
April 2023 
Third 
week of 
April 2023 
Fourth 
week of 
April 2023 
First week 
of May 2023 
August 2023
 
 
 
 

 
Study Product Guidelines and Considerations 
57 of 57 
Version 1.1 
 
 
13 November 2020