Comparative Effectiveness of Pain Cognitive Behavioral Therapy and Chronic Pain Self-Management Within the Context of Opioid Reduction: The EMPOWER Study
Phase: NA
Conditions: Chronic Pain
Sponsor: Stanford University

  
 
 
Study Protocol for Comparative Effectiveness of Pain Cognitive Behavioral Therapy and Chronic Pain Self-
Management Within the Context of Opioid Reduction: The EMPOWER Study  
 
 ClinicalTrials.gov: NCT03445988 
 Date: 09/19/2023 
 
 Table of Contents  
 
Project Summary .........................................................................................................................2 
General Information ....................................................................................................................2 
Study Goals and Objectives ........................................................................................................3 
Study Design ...............................................................................................................................3 
Methodology ...........................................................................................................................3–5 
Study Outcomes ..........................................................................................................................5 
Study Arms .................................................................................................................................6 
Sample Size Calculations and Study Power............................................................................ 6-7 
Statistical Analysis Plan .......................................................................................................... 7-8 
Appendix A. Data Measurement Plan .......................................................................................10 
Appendix B. Stanford Informed Consent Form ..................................................................11–22 
References .................................................................................................................................23 
 
 

 
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Project Summary 
The purpose of this pragmatic clinical trial is to transform care, reduce health risks, and improve outcomes for patients with chronic pain who 
are taking long-term prescription opioids. Our proposed study will address several critical evidence gaps that currently hinder patients and 
physicians from making informed decisions about pain care. This project will provide both patients taking opioids and their prescribers with the 
specific evidence needed to choose the most effective strategies for reducing opioid doses and minimizing pain, reducing pain interference, and 
improving role function. 
 
For patients interested in reducing opioid use, we aim to: (1) reduce prescription opioid use while maintaining pain control; and (2) compare 
the effectiveness of the Chronic Pain Self-Management Program (CPSMP), cognitive behavioral therapy for chronic pain (pain-CBT), and no 
behavioral treatment, all within the context of patient-centered collaborative opioid tapering. The acronym EMPOWER stands for Effective 
Management of Pain and Opioid-Free Ways to Enhance Relief. 
 
[Please note: Along with the EMPOWER randomized controlled trial, PCORI funded a separate sub-study involving a national observational 
study of people taking daily prescription opioids (not tapering). As this observational sub-study was not part of the randomized controlled trial, 
it is not described in this protocol.] 
 
General Information 
 
Stanford University Institutional Review Board (IRB) Protocol Title: Comparative Effectiveness of Pain Cognitive Behavioral Therapy and 
Chronic Pain Self-Management Within the Context of Opioid Reduction 
 
Stanford University IRB eProtocol #44918 
 
Protocol Approved: 03/27/2018 
 
ClinicalTrials.gov: NCT03445988 
Trial Registration: 02/26/2018 
Protocol Access: https://clinicaltrials.gov/study/NCT03445988 
 
Funding: Patient-Centered Outcomes Research Institute (PCORI®) Award: OPD-1610–37007 
 
Project Principal Investigator: Beth Darnall, PhD; Professor of Anesthesiology, Perioperative and Pain Medicine at Stanford University School 
of Medicine. Dr. Darnall is Director of the Stanford Pain Relief Innovations Lab. 1070 Arastradero Road, Ste 200, MC5596, Palo Alto, CA 
USA 94304. Email: bdarnall@stanford.edu 
 
Project Manager: Luzmercy Perez, BA. Stanford Pain Relief Innovations Lab. 1070 Arastradero Road, Ste 200, MC5596, Palo Alto, CA USA 
94304. Email: luzmercy.perez@stanford.edu 
 
Statistician: Lu Tian, PhD; Professor of Biomedical Data Science (and by courtesy) Statistics at Stanford University School of Medicine. 
Email: lutian@stanford.edu 
 
Biostatistician: Juliette Hong, MS; Anesthesiology, Perioperative and Pain Medicine at Stanford University School of Medicine, 1070 
Arastradero Road, Ste 200, MC5596, Palo Alto, CA USA 94304. Email: jhong5@stanford.edu 
 
 
 
 

 
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Study Goals and Objectives 
 
Aim 1: Reduce or Contain Prescription Opioid Use While Maintaining Pain Control. 
Hypothesis 1a. At one year, 40% of participants in the Taper Only group (no behavioral treatment) will successfully reduce prescription 
opioids by ≥50% in MEDD without worsening pain intensity, pain interference, or satisfaction with social roles and activities at 12 months. 
Hypothesis 1b. Success with patient-centered opioid tapering will not be associated with the starting MEDD. 
 
Aim 2: Compare the Effectiveness of (1) Taper + CPSMP, or (2) Taper + pain-CBT, or (3) No Behavioral Treatment (Taper Only) within 
the Context of Patient-Centered Collaborative Opioid Tapering. 
Hypothesis 2a. Participants receiving behavioral interventions (Taper + pain-CBT or Taper + CPSMP) will be more likely to reduce their 
opioid dose than those in the Taper Only group (no behavioral intervention). 
Hypothesis 2b. There will be no significant differences in dosage reduction or the percentage of participants reducing dosage between the 
Taper + pain-CBT and Taper + CPSMP groups. 
Hypothesis 2c. Participants in the Taper + pain-CBT group will experience less pain, less pain interference, and decreased depression 
compared to those in the Taper + CPSMP or Taper Only groups. 
Hypothesis 2d. Participants in the Taper + CPSMP group will show greater improvements in satisfaction with social roles and activities 
and self-efficacy compared to those in the Taper + pain-CBT or Taper Only groups. 
 
Exploratory Hypothesis 2e. Opioid escalation will be less common among participants in the behavioral intervention groups (Taper + pain-
CBT or Taper + CPSMP) compared to those in the Taper Only group. 
 
Study Design 
 
This is a pragmatic, prospective, longitudinal, multi-center, three-arm, randomized controlled clinical trial. The study will include 594 
patients receiving daily prescription opioids in primary care and pain clinics at EMPOWER study sites (see Table 1 for a list of study 
locations). 
 
    Table 1. Study Sites  
 
Study Site 
Setting 
Payer System 
Type 
Location 
Stanford Pain Management Center 
Pain Clinic 
Open 
Academic Regional Org. 
Redwood City, CA 
Stanford Primary Care 
Primary Care 
Open 
Academic Regional Org. 
Palo Alto, CA 
Phoenix Veterans Affairs Health Care System 
Pain Clinic 
Closed Network 
Veteran Healthcare 
Phoenix, AZ 
Stieg Pain Clinics/MedNOW Clinics 
Pain Clinic 
Open 
Private Practices 
Colorado 
Intermountain Health 
Primary Care 
Closed Network 
Regional Org. 
Layton, UT 
Kaiser Permanente Oakland 
Primary Care 
Closed Network 
Regional Org. 
Oakland, CA 
Lehigh Valley Health Network 
Pain Clinic 
Closed Network 
Regional Org. 
Allentown, PA 
 
Methodology 
 
At all sites, patient recruitment will occur through the following methods: identifying eligibility in medical records, in-house advertising, 
external community-based advertising, and use of the CHOIR database at Stanford University.1 Study coordinators will review the clinic 
schedule daily to identify eligible patients based on pain and opioid information available in the electronic medical record. Clinicians will 
discuss EMPOWER with patients and obtain permission from interested patients to be contacted by study staff. Study coordinators will 
then obtain informed consent and register participants in the CHOIR research learning health system database to initiate survey 
deployment. After completing the baseline survey, participants will be randomized to one of three intervention arms: (1) EMPOWER 
Taper Only (no behavioral treatment); (2) EMPOWER Taper + pain-CBT; or (3) EMPOWER Taper + CPSMP. Block randomization with 
variable block sizes, stratified by study site, will be utilized. The Executive Research Team, including the Principal Investigator and the 
data analytic team, will remain masked to intervention assignment throughout recruitment, enrollment, and data collection. Participants, 
EMPOWER clinicians, and study coordinators will be aware of intervention assignment. For the study flow diagram, see Figure 1. 
 
 

 
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Figure 1. Study Flow Diagram 
 
 
 
Eligibility Criteria. Inclusion criteria are: adults aged 18–85 years, diagnosed with chronic non-cancer pain (lasting at least six months), 
and actively taking prescription opioids (at least 10 MEDD) for at least three months at any of our seven study sites. Eligibility will not be 
restricted to specific pain conditions. Exclusion criteria include: clinician-determined moderate or severe opioid use disorder (OUD) as 
defined by a brief screening tool;2 inability to provide informed consent; inability to meaningfully participate in group interventions (e.g., 
due to cognitive impairment or lack of English fluency); or known disruptive behavior that could interfere with the group learning 
experience and treatment outcomes for the cohort. Patients with moderate to severe OUD will be referred for addictionology consult or 
triaged per local systems. 
 
Patients with active substance use disorder (SUD) may enroll and local systems will refer them for SUD evaluation and treatment as 
clinically indicated. No special vulnerable populations will be recruited (e.g., children or patients pregnant at the time of enrollment). All 
research procedures will take place at the seven clinical sites, with data collection and some treatment elements occurring online. 
 
Consent Procedures. Electronic consent will be administered through CHOIR1 following completion of the screening visit. Participants 
will provide consent by entering their full name and date on the consent form webpage in CHOIR after reviewing the form with study 
staff. A copy of the consent form will be securely emailed to the participant. Two study sites (Phoenix Veterans Affairs Health Care 
System and Kaiser Permanente Oakland) will administer consent locally. 
 
Participant Compensation. Participants will receive a $25 Amazon gift card code for completing assessments at baseline, month 6, and 
month 12, and $5 for completing weekly surveys from weeks 1–24 and monthly surveys from months 7–11 (29 total surveys).Total 
possible compensation for study participation is $220. For participants who do not complete their 12-month survey and do not respond to 
any of the contact attempts made by the study team including the EMPOWER clinician we will offer an additional $50 incentive for 
completing the last survey.  
 
Learning Health System and Informatics Platform. CHOIR (https://choir.stanford.edu/) is an electronic informatics platform that serves 
multiple study functions.1 It is a secure (password-protected), HIPAA-compliant platform hosted by the Stanford University School of 
Medicine. CHOIR will collect patient-reported data at each time point using surveys tailored to the study and will be standardized across 
all study sites. Additional CHOIR functions include obtaining online consent, automated post-enrollment randomization, deployment of 
tailored surveys based on treatment arm assignment, a patient-reported outcomes data system that minimizes response burden using 
computer adaptive testing for NIH PROMIS measures, a centralized study database, an automated electronic payment system for survey 
completion, real-time display of patient progress for study clinicians, generation of personalized opioid tapering plans, monitoring for 
patient adverse events, and deployment of alerts to various stakeholders to address patient risks, minimize missing data, and manage 
participant payments. Clinicians will be able to view individual patient progress and longitudinal data in real time. Paper surveys will be 
mailed to participants who lack access to email, computers, or smartphones, and study staff will input the data into the electronic database. 

 
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Weekly CHOIR surveys: All patients will receive weekly CHOIR e-surveys via email to assess taper discomfort symptoms or other issues, 
with the explicit purpose of informing clinical care, symptom triage, and any necessary adjustments to their taper plan. Taper-related 
symptoms of moderate severity will trigger an automated e-alert to the prescriber, study site director, site coordinator, and study manager. 
Patients will also receive automated e-response messages with recommended actions, such as calling the clinic for telephone triage or 
scheduling an in-clinic visit. At each follow-up visit, taper discomfort symptoms will be reviewed and confirmed by the prescribing 
clinician as either related or unrelated to the taper. Moderate and severe symptoms will be reported to the local IRB, the Data Safety and 
Monitoring Board (DSMB), and the study sponsor. 
 
Monthly CHOIR surveys: Patients will be assessed monthly for satisfaction with the study, current opioid use, hospital or emergency 
medical visits, depressive symptoms, suicidality, and other factors that may indicate symptom worsening and require follow-up. 
Suicidality will trigger e-alerts to the prescribing clinician, site director, site coordinator, study manager, and the overall principal 
investigator. Site-specific messages will provide patients with instructions for non-emergency triage (e.g., calling the clinic for telephone 
or in-person follow-up) and emergency triage options in their community (e.g., calling 911), rapid contact with clinic staff, and crisis 
hotlines.  
 
Weekly and monthly surveys will ensure careful monitoring of patients, triage of issues, and close connections with study staff and 
prescribing providers to enable rapid taper adjustments and address any additional needs. Study clinicians may securely access 
EMPOWER CHOIR via a web browser to review patient responses and coordinate participant activities. Comprehensive patient-reported 
survey batteries will be administered at baseline and at six and 12 months, including data on opioid use.  
 
Randomization. Each site will conduct a site-specific randomized controlled trial using a randomized design, allowing rapid accrual of 
patient cohorts (N=8–18 per cohort) assigned to the same intervention arm and timely delivery of behavioral interventions. Patients 
entering the study will be automatically assigned to the currently open intervention arm. The ordering of intervention arms will remain 
blinded to patients and clinicians, who cannot choose or direct group assignment. Study coordinators, while unblinded, will be trained to 
maintain clinician and patient blinding. After enrollment and baseline measures, group assignments will be revealed to participants. A 
statistician unaffiliated with patient care will create unique randomization schemes for each site, enabling prompt receipt of behavioral 
interventions for those assigned to such arms (ideally within two to ten weeks of taper initiation). Behavioral intervention timing will be 
recorded. 
 
Study Outcomes 
Primary Outcome (Aim 1) – Taper Success at 12 months 
Taper success will be defined as a ≥50% reduction in MEDD from baseline to 12 months without significant pain intensity increase (≤1-
point increase) or no opioid increase with significant pain relief (≥2-point decrease in pain intensity). Please see Appendix A, Data 
Measurement Plan, for more details. 
 
Secondary Outcomes (Aim 2) – Pain Characteristics for the Three Intervention Arms at 12 months 
Taper success (MEDD and pain intensity), pain interference, pain self-efficacy, and depression and satisfaction with social roles and 
activities will be assessed (for more details, see Appendix A). Specifically, depression and satisfaction with social roles and activities will 
be assessed using National Institutes of Health PROMIS short-form measures which are commonly used in pain research. These domains 
were identified by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials as core outcomes.3,4 Web-based 
PROMIS assessment center software will calculate short-form T scores using Item Response Theory scoring algorithms that apply the 
Bayesian expected a posteriori method.  
 
EMPOWER Patient-Centered Opioid Taper (received by all three study arms). Following study enrollment, all participants will engage 
with their EMPOWER clinician in a patient-centered prescription opioid tapering program. All opioid prescribing will be managed by the 
EMPOWER clinician. Opioid dose data will be sourced from study surveys and the patient’s electronic medical record. All aspects of 
tapering will be individualized, including the timing of taper initiation, the dose reduction goal (set collaboratively with the patient), and 
the pace of the taper. The basic patient-centered opioid taper protocol will mirror the pilot methods described in Darnall et al.5 Importantly, 
complete opioid cessation will only be a goal if the patient chooses it. The recommended taper speed will be a 5% reduction of the starting 
dose, with one dose decrease per month until the patient is stable, without physical discomfort or psychological distress. Patients will be 
assessed at each visit; dose decreases or increases in taper speed will only occur after consultation with and consent from the patient. 
Patients will have the choice to set the pace of their taper, pause their taper, or withdraw from the taper or the study at any time. The taper 
will not be unidirectional: EMPOWER will not restrict needed opioid increases for acute pain or for patients with poor responses to the 
taper. Participation in the study will not prevent patients from receiving any needed medical care. Patients will not be removed from the 
study if they increase their opioid dose; on the contrary, we will seek to follow these patients to understand their experiences, responses, 
and unmet treatment needs. 
 
Clinicians may use the electronic CHOIR opioid taper tool to create a taper schedule that remains flexible based on patient responses to 
prior dose reductions. Micro-dose reductions will be recommended for the first few decrements, followed by dose reductions as tolerated, 
not exceeding a 10% opioid dose reduction per month. Recommendations will include tapering one opioid at a time and avoiding 

 
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concurrent tapering of other medications. Participants will receive in-person or online medical follow-ups with their EMPOWER clinician 
approximately every three to four weeks. Participants will complete weekly and monthly CHOIR symptom surveys, which will be 
reviewed during medical follow-ups to determine whether reported withdrawal symptoms are related to the taper or are unrelated (e.g., 
seasonal allergies). If CHOIR detects severe or worsening symptoms indicative of participant struggle or deterioration, immediate (real-
time) electronic alerts will be sent to the participant, clinic, and prescribing clinician, with follow-up actions based on symptom severity.  
 
The study protocol will encourage the use of adjuvants within the scope of normal clinical practice and training and will not restrict other 
analgesic prescribing, such as initiating SNRI medications. The protocol will provide guidance on reducing short- and long-acting opioids 
and recommend tapering one medication at a time. Concurrent tapering of other medications will be discouraged.  
 
The EMPOWER taper program may only be administered by a prescriber clinician trained in EMPOWER methods. 
 
CHOIR Opioid Taper Tool. EMPOWER will include an electronic taper calculator allowing clinicians to input the patient’s current dose, 
number of daily doses, desired taper timeframe, taper goal, and taper pace. The tool will generate precise guidance for doses/pills per dose 
daily over several months. Because the taper will be flexible, the opioid taper tool can be used multiple times to recalculate a patient’s 
taper plan based on new circumstances, such as a desired taper pause or a patient’s request to adjust the taper speed.  
 
Study Arms 
(1) EMPOWER Taper + Cognitive Behavioral Therapy for Chronic Pain (pain-CBT).6 Pain-CBT is a behavioral treatment that reduces 
chronic pain and its impacts through patient education, skills acquisition, and social support. Research on pain-CBT indicates benefits for 
reducing pain intensity, pain catastrophizing, depression, and the social impact of pain.7 CBT is considered the gold-standard 
psychobehavioral treatment for pain, with other behavioral treatments demonstrating non-inferiority but not superiority.8-9 A general pain-
CBT therapist manual and corresponding patient workbook were developed for the EMPOWER study (EMPOWER CBT). A relaxation 
MP3 audio file accompanies the patient workbook. Consistent with general pain-CBT, the EMPOWER CBT protocol includes interactive 
discussion, pain education, relaxation training practice, goal setting, cognitive restructuring, problem-solving, and action planning, with 
home exercises incorporated into each session. Participants will learn to effectively manage their pain and symptoms while working 
towards achieving the goals that matter to them. A mental health will deliver the eight-week group intervention to cohorts of patients 
(N=8–18) assigned to this arm. Intervention sessions will be delivered weekly and last two hours. To ensure consistency across all study 
sites and cohorts, therapists will be trained in the common eight-session CBT protocol, with competency assured by Director Dr. Heather 
King. The structured format of the CBT intervention ensures treatment fidelity, with the trained therapists using PowerPoint slides (for 
didactic content), corresponding worksheets from the participant workbook, and optional reading from an additional book. The study 
coordinator will be present at each treatment session and facilitate intervention fidelity by ensuring participants have corresponding 
materials, including the relaxation audio. Participants assigned to this intervention arm will not receive CPSMP during the study period. 
No other aspects of pain care will be constrained. 
 
(2) EMPOWER Taper + The Chronic Pain Self-Management Program (CPSMP).10-11 CPSMP is an evidence-based behavioral 
treatment delivered by two certified healthcare clinicians or peer co-leaders with lived experience in successful pain self-management. 
Certification as a CPSMP leader requires 24 hours of training over four days. The CPSMP manualized protocol includes patient education 
about pain and strategies for effective self-management of pain, its impacts, and other symptoms. Based on self-efficacy theory, CPSMP is 
delivered in six weekly 2.5-hour group sessions to cohorts of 8–18 participants. All participants receive a book on pain self-management 
and an exercise CD. Like pain-CBT, CPSMP incorporates interactive discussions, relaxation training, action planning, and home exercises 
into each session. Patients learn to live better with chronic pain by making daily choices that support improved health and function. 
Participants assigned to this arm will not receive group pain-CBT during the study period. No other aspects of pain care will be 
constrained, including individual psychological treatment; receipt of non-study treatments will be tracked. 
Prior research has shown that pain-CBT and CPSMP have both shared and distinct effects, suggesting some individuals may respond 
better to one treatment than the other. However, no evidence currently exists to guide a best-practice choice between the two. While pain-
CBT and CPSMP are both effective for chronic pain, they have not been tested within an active opioid reduction protocol. We hypothesize 
that these behavioral interventions will help patients reduce opioids and associated risks, manage pain, and restore function in ways 
superior to opioid reduction alone. 
  
(3) EMPOWER Taper Only (usual care). Participants assigned to this intervention arm will participate in the voluntary EMPOWER 
patient-centered opioid tapering program and will not receive group pain-CBT or CPSMP during the 12-month study period. No other 
aspects of pain care will be constrained.  
 
Virtual Format for Behavioral Treatment Groups  
Background: In March 2020, the COVID-19 pandemic led to social distancing safety requirements, which prevented the continuation of in-
person delivery of our behavioral treatment groups. In response, with PCORI approval, we demonstrated the feasibility of virtual groups by 
piloting a virtual option with participants who were already enrolled in the study (i.e. enrolled prior to 03/26/2020). We now offer virtual 
(live, online) delivery of our behavioral treatment groups as another option for all participants including new enrollments. Due to ongoing 
and unpredictable COVID-19 restrictions on group gatherings, live virtual treatment delivery is essential to ensure successful completion of 
our RCT.  

 
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Content: Virtual pain-CBT and CPSMP treatments are delivered exactly as outlined in the protocol where the same content and materials 
(e.g., participant workbooks, presentation slides, etc.) by live facilitators with live participants. The only difference between virtual and in-
person is the video format in the virtual groups and materials are distributed via traditional mail instead.  
 
Platform – Each site delivers the virtual treatments using a HIPAA compliant and secured platform endorsed by their respective institution 
(Zoom at Stanford and Colorado, VA Video Connect at the Phoenix VA, and WebEx at Intermountain Health). The platforms are broadly 
utilized for telehealth at the sites. 
 
Facilitator Training – To assure high-quality and standardized delivery, the facilitators who conduct the in-person groups at each site, are 
also the same facilitators delivering the virtual treatments. Additionally, we centralized our virtual system across Stanford Pain, Stanford 
Primary Care and Colorado where we have Stanford psychologists (or Telligen peer leaders) leading a cohort comprised of both Stanford 
and Colorado participants. As closed payer systems, Phoenix VA and Intermountain Health do not permit external services. The facilitators 
practiced delivering the programs on the virtual platform up to three times before the start of the first series.  
 
Participant Training – The facilitators, study coordinators, and the core manager collaborated in developing materials to prepare participants 
to successfully engage in the virtual groups. Before the first session, the local study coordinator conducts an orientation with each 
participant to review how to use the platform and etiquette expectations (e.g., be situated in a private, quiet place during each session). 
Please see accompanying documents (Study Coordinator Procedures/Script, Group Telehealth Agreement, Facilitator Work Flow and 
Guidelines, Welcome to the Group, Welcome Letter, and Zoom Application Instructions). 
 
Patient-Centered Opioid Tapering (taper-only, no behavioral treatment) 
Virtual Format - Each recruitment site enhanced their clinic schedules to make virtual medical visits more accessible to patients at the onset 
of the COVID-19 pandemic in March 2020. Participants continue to have the option to schedule an in-person or virtual appointment for their 
follow-up visits with their EMPOWER clinician. All sites had an established telehealth system, which allowed a smooth transition into 
conducting more virtual visits. Video and messaging features are included in the telehealth system. For participants who do not have access 
to a smartphone or computer, the Phoenix VA loans tablets to patients to address this issue. 
 
Institutional Review Board (IRB). The study will adhere to the common protocol and procedures approved by local IRBs at all study sites. 
 
Sample Size Calculations and Study Power 
 
The power calculation is primarily based on the study aims for comparative effectiveness. The original power calculation was for N = 850, 
with N = 750 patients completing the month-12 survey. The study sample size was later reduced to N = 489 participants completing the 
month-12 survey (n = 163 patients per intervention arm on average). As a result, the study's power is lower than initially planned but 
remains adequate for the objectives, summarized as follows: 
Hypothesis 1a. N = 163 Taper Only participants provide 80% power to confirm that the taper success rate is above 40% at a two-sided 
significance level of 0.05, when the true success rate is 51.5%.  
Hypothesis 1b. Comparing the taper success rate between n = 140 Taper Only participants with an initial dose < 200 MEDD and n = 23 
Taper Only participants with an initial dose ≥ 200 MEDD, the expected 95% confidence interval (CI) for the difference in success rates 
is [-22%, 22%], assuming a true taper success rate of 50% independent of the initial dose. The width of the CI increases by only 24% due 
to the sample size reduction.    
Hypothesis 2a. N = 163 participants per intervention arm provide 80% power for detecting a taper success rate difference of 40% versus 
53.5% at a two-sided significance level of 0.05.  
Hypothesis 2b. N = 163 participants per intervention arm yield an expected 95% CI of [-11%, 11%] for estimating the difference in taper 
success rates between the Taper + pain-CBT and Taper + CPSMP arms, assuming a taper success rate of 50% in both arms.  
Hypothesis 2c and 2d. N = 163 participants per intervention arm provide 80% power to detect a between-group difference of 0.311 
standard deviation in the 12-month change of continuous outcomes using a two-sample t-test at a two-sided significance level of 0.05.  
 
We also assume an annual drop off rate is less than 19% and we will include all drop outs in our ITT analyses. We will enroll a total of 594 
patients to assure the minimum group size requirements for analysis of comparative effectiveness. 
 
Statistical Analysis Plan 
 
Aim 1: Reduce or contain prescription opioid use while maintaining pain control. 
Hypothesis 1a: We will estimate the proportion of patients achieving patient-centered opioid taper success and test whether this proportion 
exceeds 40% (treatment success estimate derived from Darnall et al.5). We will estimate the binomial proportion of patients with opioid 
taper success and use the exact test to test whether the proportion is greater than 40%.  
Hypothesis 1b: We will compare opioid tapering success rates among patients in different initial opioid dose categories: Low (10–49 
MEDD), Moderate (50–89 MEDD), High (90–199 MEDD) and Super-High (≥200 MEDD). 
 

 
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Aim 2: Examine the balance in key patient characteristics such as initial opioid dose, pain intensity, and functional measures separately for 
the three interventions arms. We will use Chi-square or Fisher's exact tests to compare success rates between opioid dose groups. 
Hypothesis 2a: We will compare the intervention success rate of 500 patients in behavioral intervention arms (pain-CBT and CPSMP) with 
250 patients receiving patient-centered opioid tapering only (no behavioral intervention; Taper Only). We will use a Chi-square test to 
compare the success rate between groups. We will apply logistic regression to adjust for baseline covariates. 
Hypothesis 2b: We will estimate the difference in intervention success rates between pain-CBT and CPSMP arms using an intention-to-
treat procedure and construct 95% CIs for the difference.  
Hypothesis 2c: We will compare changes in pain intensity, pain interference, and depression scores (baseline to 12 months) between the 
pain-CBT and Taper Only as well as between the pain-CBT and CPSMP arms using two-sample t-tests. We will apply an analysis of 
covariance based on multiple regression to adjust for baseline covariates. 
Hypothesis 2d. We will compare improvements in satisfaction with social roles and activities, and self-efficacy for Taper + CPSMP against 
Taper + pain-CBT and Taper Only. 
 
We will compare the intervention success rate between participants who received the behavioral interventions with participants who 
received Taper Only using Fisher’s exact test. The difference in success rates between Taper + pain-CBT and Taper + CPSMP will be 
assessed with 95% confidence intervals (CI) to determine equivalence. Secondary outcomes—including pain intensity, pain interference, 
depression, self-efficacy, and satisfaction with roles and activities—will be compared between Taper + pain-CBT and Taper Only and 
between Taper + pain-CBT and Taper + CPSMP at months 6 and 12 using mixed effects model for repeated measurements regression. 
This analysis will incorporate baseline, month 6, and month 12 outcomes as dependent variables, with an unstructured variance–covariance 
matrix for within-subject correlations.   
 
Exploratory Hypothesis 2e: We will separately estimate the probability of opioid escalation by intervention arm (pain-CBT, CPSMP and 
Taper Only).  
 
For exploratory hypotheses, the probabilities of opioid escalation by intervention group will be estimated and compared with Fisher’s exact 
test. Post-hoc analyses will use logistic regression to examine associations between baseline characteristics and tapering success. There is 
no correction for multiple comparisons. Heterogeneity of treatment effects will be explored by splitting the population into training and 
validation sets of equal sizes. Logistic regression with lasso regularization will identify baseline features predicting tapering success in 
each intervention group. These models will be applied to testing sets to identify the subgroup with the highest predicted success under 
Taper + pain-CBT, and success rates will be compared across intervention arms within the subgroup. Intervention effects will be also 
estimated in predefined subgroups.   
 
Heterogeneity of treatment effects will be explored for each intervention arm considering gender, age, race, initial opioid dose, baseline 
depression, and anxiety level. 
 
Access and Intervention Participation. The comparison across interventions will be performed according to the intention-to-treat principle. 
Additional comparisons based on the actual intervention received will be conducted as a sensitivity analysis. We will also study the effect 
of intervention participation and on treatment outcomes. To this end, we will perform regression analyses to examine the association 
between the success rate for opioid weaning and other outcomes with session attendance for the pain-CBT and CPSMP arms, separately, 
while adjusting for identified confounding factors affecting compliance. We will also investigate how baseline factors, such as 
socioeconomic status, affect the level of compliance.  
 
Virtual Behavioral Treatment Groups: Comparison of participants who receive in person vs. virtual treatment - We will examine mode of 
delivery as a potential covariate in our analytic models, and study statistician Lu Tian will both advise and implement. Outside of this issue 
of treatment delivery mode, we must also recognize that COVID itself has introduced a new variable in the study. We will be examining 
COVID impacts, as well. In regards to the group size and effectiveness of the intervention, the size of the virtual groups are comparable to 
the size of the in person groups where most groups have an average size of 4 participants. Facilitators stated larger groups (more than 4 
participants per cohort) usually provide a more dynamic experience with diverse interactions. While in smaller groups, participants have a 
chance to go into more detail regarding the skills they are learning and using and any barriers that arise.   
 
Sensitivity Analysis. We will perform sensitivity analyses to account for missing data and non-completion of behavioral interventions. In 
addition, we will consider an alternative definition of taper success, replacing the 50% reduction in opioid dose with a 30% reduction in 
opioid dose. A 30% change has been cited as a benchmark for a moderately clinically important difference in the chronic pain literature. 
Similar analyses will be conducted with this new endpoint as part of the sensitivity analyses. 
 
Statistical analysis will be completed using SAS Enterprise Guide Version 8.3 and R Version 4.1.1. 
 
Project Management 
 
As the principal investigator, Dr. Darnall oversees the project along with the site co-investigators (Drs. De Bruyne, Edelson, Flood, Kim, 
Mackey, Mardian, Moore, Nicholson, and Porter). Luzmercy Perez serves as the project manager. Additional study staff include Corinne Jung, 

 
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who facilitates IRB regulation, and study coordinators. Juliette Hong assists with statistical analyses and organization under the supervision of 
Prof Lu Tian. The study site IRBs provide local regulatory compliance oversight. An independent Data Safety and Monitoring Board will meet 
twice yearly to review the project status and adherence to the Data Safety and Monitoring Plan.  
 
Ethics 
As detailed in the Safety Considerations section, ethical considerations include the potential (though unlikely) discomfort when completing 
surveys. This is addressed by making all survey items optional. For increased withdrawal symptoms, a plan to triage participant needs has been 
outlined.  
 
Informed Consent Forms 
The approved Informed consent form is included below (see Appendix B). 
 
 
 

 
10 
 
Appendix A. Data Measurement Plan 
 
 
 
Name of Measure 
 
 
 
 
 
Brief Measure Description 
 
Baseline 
Weekly 
(first 6 
months) 
Monthly* 
 
Months  
6, 12 
Pain 
Catastrophizing 
Scale (PCS)12-13 
13-item scale assesses severity of trait pain catastrophizing tendencies on a 5-
point scale (0 = “not at all”; 4 = “all the time”). 
x 
 
 
x 
Pain Self-Efficacy 
Questionnaire 
(PSEQ)14 
2-items measure self-confidence to manage pain and engage in life activities 
despite pain. 
x 
x 
x 
x 
NIH PROMIS 
Measures 
 
Pain intensity (one-item rates average pain intensity during the previous 7 
days on a scale of 0 (no pain) to 10 (worst pain imaginable);15-16 depression; 
and satisfaction with social roles and activities (The National Institutes of 
Health Patient-Reported Outcomes Measurement Information System short 
form versions will be used to assess depression and satisfaction social roles 
and activities. Questions will be framed according to the experience of 
symptoms or functioning over the past 7 days, and higher scores signify 
greater severity of these symptoms. Scores will converted from raw scores to 
t-scores (M = 50 and SD = 10), consistent with their initial publications).17-18  
x 
x 
x 
x 
Taper collaboration 
Patients rate how much their input was considered by their doctor and overall 
collaboration in their opioid taper. 
x 
x 
x 
x 
Alcohol & 
Substance Use 
AUDIT alcohol abuse screen,19 DAST illicit drug abuse screen, tobacco use.20 
x 
 
 
x 
New Medical 
Problems or Surgery 
New medical issues are assessed, such as dental surgery that might cause a 
new opioid prescription. 
x 
 
x 
x 
Subjective Opioid 
Withdrawal 
Symptom Scale 
(SOWS)21 and 
correlates 
Weekly for the first 6 months questions will assess mood, anxiety, sleep, 
physical function, pain interference, medication use, discomfort with opioid 
reduction, and any emergent medical problems.  
 
x 
x  
 
x 
 
Beck Depression 
Inventory22 (single 
suicide risk item) 
This question is deployed at baseline and also prompted in the weekly survey 
(SOWS) when the PROMS depression question is answered with “often” or 
“always”.  
x 
 
x 
x 
Group Intervention 
Attendance 
Pain-CBT and CPSMP participants will report whether they attended their 
treatment class in the past week (attendance also recorded by staff). 
 
x** 
x** 
 
Satisfaction with 
Group Intervention 
Pain-CBT and CPSMP participants will rate their level of satisfaction with 
their assigned intervention, and separately, with their group instructor on a 7-
point rating scale (0 = “not at all satisfied” to 6 = “extremely satisfied”).  
 
x*** 
 
x*** 
 
 
Life Changes survey 
Items assess changes to employment, disability status, and/or major life events 
(new child, loss of a loved one, divorce, major illness, etc.). 
 
 
 
x 
Study Satisfaction 
Patients will rate their level of satisfaction with the study (0 = “not at all 
satisfied” to 6 = “extremely satisfied”). They may input free text responses and 
we will monitor these closely. 
 
 
 
x 
Study Effects 
Assesses patient-reported effects (positive and negative) as a result of 
participating in the study. 
 
 
 
x 
Patient’s Global 
Impression of 
Change (PGIC)15  
Single item assessing patient’s impression of general improvement as a result 
of participating in the study. 
 
 
 
x 
COVID-19 
Assesses impact of COVID-19 on participants.  
x 
 
x 
x 
Pain Interference 
A nine-item Brief Pain Inventory questionnaire measures the level of pain-
related interference during the past twenty-four hours across seven domains 
(such as mood, general activity, etc.) on a scale of 0 (does not interfere) to 10 
(completely interferes). Higher scores signify worse pain interference. A total 
pain interference score will be created by averaging the seven domain scores 
for each participant.23-24 
x 
 
x 
x 
Opioid Dose  
Participants will self-report their daily prescribed opioid type(s) and dose(s). 
Daily opioid doses will be converted to a total standardized morphine 
equivalent daily dose (MEDD) using the 2016 CDC Guidelines for conversion 
factors including using the escalation of the factor for methadone (i.e. 
methadone’s conversion factor increases at higher doses).25 
 
 
 
 
* Monthly questionnaires will be distributed at months 1–5 and 7–11. They will not be distributed at months 6 and 12.  
** Group Treatment Attendance Form will only be completed while participant is currently in pain-CBT or CPSMP interventions.  
*** Satisfaction with Group Intervention Form will be distributed following the first and final session of the intervention course only.  
 
 

 
11 
 
Appendix B. Stanford Informed Consent Form 
 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director:  Dr. Beth Darnall 
Protocol Title:   Opioid Taper Study  
 
This is a study for people who want to use less or no opioids. A health care professional will 
help everyone slowly taper their opioids. You will have a say in the speed of the taper. The 
EMPOWER study is funded by the Patient-Centered Outcomes Research Institute (PCORI, 
https://www.pcori.org/) 
In addition to tapering, everyone will be randomized to either: 
• 
Cognitive Behavioral Therapy for Chronic Pain 
• 
Chronic Pain Self-Management Program 
• 
No education for the first year (after that you can choose to attend either program) 
Both of the study treatment classes have been shown to help people with chronic pain live 
better lives, and have more control over their pain and symptoms. 
 
PURPOSE OF RESEARCH 
You are invited to participate in a research study of the effectiveness of the Chronic Pain Self-
Management Program (CPSMP), Cognitive Behavioral Therapy for chronic pain (pain-CBT), and 
no behavioral treatment within the context of patient-centered collaborative opioid tapering 
(PCOT). We hope to learn effectiveness of these therapies to reduce patient prescription opioid 
use while maintaining pain control. You were selected as a possible participant in this study 
because you have experienced chronic pain and are interested in reducing your prescription 
opioid use. 
 
If you decide to terminate your participation in this study, you should notify the research team 
at (650) 724-9319. 
 
This research study is looking for 865 participants experiencing chronic pain that are 
interested in voluntarily reducing their prescription opioid use. Enrollment for this study will 
take place across the Western United States. Stanford University expects to enroll 392 
research study participants. 
 
VOLUNTARY PARTICIPATION 
Your participation in this study is entirely voluntary. Your decision not to participate will not 
have any negative effect on you or your medical care. You can decide to participate now, but 
withdraw your consent later and stop being in the study without any loss of benefits or 
medical care to which you are entitled. 
 
 
DURATION OF STUDY INVOLVEMENT 
This research study is expected to take approximately 5 years to complete. Participation will 
last a total of 12 months. Participants will be asked to complete a set of questionnaires lasting 
IRB Use Only 
Approval Date:   March 22, 2022 
Expiration Date: March 22, 2023 

 
12 
 
approximately 30-60 minutes at baseline, 6, and 12 months. For the first 6 months each 
participant will also be asked to complete weekly questionnaires lasting approximately 10 
minutes. For the final 6 months of participation, we will send out monthly questionnaires 
similar in nature and content to the weekly questionnaire.   
 
 
PROCEDURES 
If you choose to participate, Dr. Beth Darnall and her research study staff will ask you to 
participate in the following steps. 
Step 1: Eligibility Visit 
The first step is to confirm your eligibility with the research team. This is to make sure you are 
a good fit for the study. Once your eligibility is confirmed and you have signed this consent, 
you will be asked to fill out a battery of questionnaires assessing medication use, pain and 
symptoms, coping mechanisms, mood, sleep, general health and well-being, and psychological 
traits. This set of questionnaires take approximately 30-60 mins to complete. 
At this visit, we will also mark the launch of the brief weekly questionnaires (e.g., 12 items). 
The weekly questionnaires will be administered weekly for the first 6 months of study 
participation and will include assessments of patient symptoms, satisfaction, and side effects 
of the opioid taper program. For the final 6 months of participation we will send out monthly 
questionnaires similar in nature and content to the weekly questionnaire. All questionnaires will be 
administered online to reduce participant burden. 
Step 2: Opioid Taper 
All participants engaging in a patient-centered opioid taper will collaborate with their physician 
to determine the strategy of the tapering program. Duration of the opioid taper is up to 12 
months to assure patient comfort, though some patients may end their taper sooner. The goal 
of the taper is to achieve the lowest comfortable dose for each patient with patients informing 
the pace of opioid reduction. 
Step 3: Intervention 
Roughly 2-6 weeks following step 1, you may be randomly assigned to one of the following 
groups. Your chance of receiving each intervention is random and determined by a number of 
factors. 
1. Pain-Cognitive Behavioral Therapy (pain-CBT+PCOT) 
A trained psychologist delivers pain-CBT to groups of patients. Group treatment is 
delivered across 8 weekly sessions that last for 2 hours each. Pain- CBT incorporates 
interactive discussion, practice of relaxation training, action planning, and home 
exercises into each session. Pain-CBT is effective for reducing pain intensity, pain 
catastrophizing, depression and social impacts. 

 
13 
 
2. Chronic Pain Self-Management Program (CPSMP+PCOT) 
The CPSMP is delivered by 2 trained peers who are certified CPSMP leaders. The CPSMP 
consists of six weekly 2-hour group sessions in which two peer co-leaders provide 
patient education about pain, effective self-management, pain impacts, and other 
symptoms from a highly structured manual. CPSMP incorporates interactive discussion, 
practice of relaxation training, action planning, and home exercises into each session. 
3. Patient-Centered Opioid Taper (PCOT) 
Participants allocated to this arm will engage in a physician-guided, patient-centered 
opioid tapering program without additional behavioral intervention. 
Step 4: Follow-up questionnaires 
6 and 12 months following enrollment you will be asked to fill out a battery of questionnaires 
similar to those completed in step 1. They will assess medication use, pain and symptoms, 
coping mechanisms, mood, sleep, general health and well-being, and psychological traits. This 
set of questionnaires take approximately 30-60 mins to complete. 
Longitudinal Arm: 
If you are not interested in participating in the interventions or reducing your current 
prescription opioid medications but are otherwise eligible and interested we may ask you to 
participate in a 12-month observational arm of the study. You will be asked to complete a 
battery of questionnaires at baseline, 6 months, and 12 months following enrollment. 
Women of Childbearing Potential 
If you are a woman who is able to become pregnant, it is expected that you will use an 
effective method of birth control to prevent exposing a fetus to a potentially dangerous agent 
with unknown risk. If you are pregnant or currently breast feeding, you may not participate in 
this study. You understand that if you are pregnant, if you become pregnant, or if you are 
breast-feeding during this study, you or your child may be exposed to an unknown risk. 
To confirm to the extent medically possible that you are not pregnant, you agree to begin the 
study after the onset of your next menstrual period. You must agree to avoid sexual 
intercourse or use a birth control method judged to be effective by the investigator and which 
will not interfere with the proposed investigation. You must accept the risk that pregnancy 
could still result despite the responsible use of reliable method of birth control. You agree to 
notify the investigator as soon as possible of any failure of proper use of your birth control 
method, or if you become pregnant, either of which may result in your being withdrawn from 
the study. 
PARTICIPANT RESPONSIBILITIES 
As a participant, your responsibilities include: 
• 
Follow the instructions of the Protocol Director and study staff. 

 
14 
 
• 
Keep your study appointments. If it is necessary to miss an appointment, please contact 
the Protocol Director or research study staff to reschedule as soon as you know you will 
miss the appointment. 
• 
Tell the Protocol Director or research study staff about any side effects, doctor visits, or 
hospitalizations that you may have. 
• 
Tell the Protocol Director or research staff if you believe you might be pregnant or 
gotten your partner pregnant. 
• 
Complete your questionnaires as instructed. 
• 
Ask questions as you think of them. 
• 
Tell the Protocol Director or research staff if you change your mind about staying in the 
study. 
 
WITHDRAWAL FROM STUDY 
If you first agree to participate and then you change your mind, you are free to withdraw your 
consent and discontinue your participation at any time. Your decision will not affect your 
ability to receive medical care for your disease and you will not lose any benefits to which you 
would otherwise be entitled. 
 
If you decide to withdraw your consent to participate in this study, you should notify the 
research team at (650) 724-9319. 
 
The Protocol Director may also withdraw you from the study without your consent for one or 
more of the following reasons: 
• 
Failure to follow the instructions of the Protocol Director and study staff. 
• 
The Protocol Director decides that continuing your participation could be harmful to you. 
• 
Pregnancy 
• 
You need treatment not allowed in the study. 
• 
The study is cancelled. 
• 
Other administrative reasons. 
• 
Unanticipated circumstances. 
 
POSSIBLE RISKS, DISCOMFORTS, AND INCONVENIENCES 
There are risks, discomforts, and inconveniences associated with any research study. These 
deserve careful thought. You should talk with the Protocol Director, Dr. Beth Darnall, if you 
have any questions. 
• 
Patients who enter the study and engage in patient-centered opioid tapering may 
experience physically uncomfortable and/or distressing opioid withdrawal symptoms 
(e.g., drug craving, anxiety, insomnia, increased pain, vomiting, diarrhea, diaphoresis, 
mydriasis, tremor, tachycardia, or piloerection). Our study is designed to mitigate these 
negative symptoms by tapering at a very slow rate and at the patient’s pace. 
• 
Patients may experience anxiety, mood changes, or greater pain with opioid changes, 
though patients may experience these symptoms as a consequence of opioid use, as 
well. 

 
15 
 
• 
A financial burden may be imposed in the form of copayments if randomization 
procedures allocate the patient to pain-CBT. 
• 
There is a low risk that patients may experience discomfort in the group treatment 
related to content or group discussions, or interpersonal interactions. 
• 
There is a risk you may feel uncomfortable answering some of the questions on the 
questionnaires. You have the right to refuse to answer particular questions. 
Additional Risks 
• 
You may be inconvenienced due to being assigned to a treatment that is not your first 
choice, or to the PCOT taper only. 
• 
Traveling may be a possible inconvenience. There are multiple sessions involved in each 
intervention. 
• 
Part of our screening process involves asking about illegal drug use. The responses to 
questions concerning illegal drug use could be self-incriminating and harmful to you if 
they became known outside the study. As explained in the confidentiality statement of 
the consent, we do not intend to disclose this information. 
• 
It is possible that based on information gained from this study, the researchers may 
have serious concerns (relating to matters such as severe depression, physical abuse, 
etc.) about your health and/or safety; in such a case, the researchers may contact you 
and provide a referral for your care. Additionally, the researchers may be required to 
report information (e.g., information relating to suicide, physical or sexual abuse) to the 
appropriate authorities. 
POTENTIAL BENEFITS 
Long-term opioid use is associated with increased pain, depression, and disability. Participants 
enrolled in the study may decrease their opioid medication use and in turn reduce their risk of 
increased pain, depression, and disability. Patients may also reduce their pain as a result of 
the interventions. 
We cannot and do not guarantee or promise that you will receive any benefits from this study. 
ALTERNATIVES 
Alternatives to tapering include switching medication class or maintaining current dose. The 
study does not constrain prescribing of any other medications while engaging in the opioid 
taper. As such, participants are free to explore any alternative procedures or standard courses 
of treatments while participating in the study. 
PARTICIPANT'S RIGHTS 
You should not feel obligated to agree to participate. Your questions should be answered 
clearly and to your satisfaction. If you decide not to participate, tell the Protocol Director. 
You will be told of any important new information that is learned during the course of this 
research study, which might affect your condition or your willingness to continue participation 
in this study. 

 
16 
 
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. 
CONFIDENTIALITY 
The results of this research study may be presented at scientific or medical meetings or 
published in scientific journals. Your identity and/or your personal health information will not 
be disclosed except as authorized by you or as required by law. However, there is always 
some risk that even de-identified information might be re-identified. 
Patient information may be provided to Federal and other regulatory agencies as required. The 
Food and Drug Administration (FDA), for example, may inspect research records and learn 
your identity if this study falls within its jurisdiction. 
 
 
 
 
 
 
 
 

 
17 
 
Authorization To Use Your Health Information For Research Purposes 
Because information about you and your health is personal and private, it 
generally cannot be used in this research study without your authorization. If 
you verbally indicate your consent, it will provide that authorization. The form is 
intended to inform you about how your health information will be used or 
disclosed in the study. Your information will only be used in accordance with this 
authorization form and the informed consent form and as required or allowed by 
law. Please read it carefully before completing it. 
What is the purpose of this research study and how will my health 
information be utilized in the study? 
The purpose of this study is to investigate the comparative effectiveness of 
group Pain-CBT and CPSMP in individuals who volunteer to participate in a 
patient-centered opioid taper program. 
The longitudinal observational arm of this study will be characterizing individuals 
who are ineligible for the opioid tapering program, either because the patient is 
disinterested in reducing their dose, or due to other factors, such as inability to 
attend treatment classes. 
Do I have to complete this authorization form? 
You do not have to provide oral authorization at the end of this oral consent 
process, but if you do not, you will not be able to participate in this research 
study, including receiving any research-related treatments. 
Completing the form is not a condition for receiving any medical care outside the 
study.  
 
If I provide authorization, can I revoke it or withdraw from the research 
later? 
If you decide to participate, you are free to withdraw your authorization 
regarding the use and disclosure of your health information (and to discontinue 
any other participation in the study) at any time. After any revocation, your 
health information will no longer be used or disclosed in the study, except to the 
extent that the law allows us to continue using your information (e.g., necessary 
to maintain integrity of research). If you wish to revoke your authorization for 

 
18 
 
the research use or disclosure of your health information in this study, you must 
write to: Dr. Beth Darnall at 1070 Arastradero Rd. Suite 200, Palo Alto Ca. 
94304 
What Personal Information Will Be Obtained, Used or Disclosed? 
Your health information related to this study, may be used or disclosed in 
connection with this research study, including, but not limited to, your name, 
contact information, demographics, date of birth, medical history, medications 
and treatment use, and responses to questionnaires. We may also access your 
medical record to obtain additional information about your pain condition, 
current and past treatments, other conditions that may affect your pain, and 
symptoms. 
Who May Use or Disclose the Information? 
The following parties are authorized to use and/or disclose your health 
information in connection with this research study: 
• The Protocol Director, Dr. Beth Darnall 
• The Stanford University Administrative Panel on Human Subjects in Medical 
Research and any other unit of Stanford University as necessary 
• Research Staff 
 
Who May Receive or Use the Information? 
The parties listed in the preceding paragraph may disclose your health 
information to the following persons and organizations for their use in connection 
with this research study: 
• The Office for Human Research Protections in the U.S. Department of 
Health and Human Services 
• The funding agency - Patient-Centered Outcomes Research Institute 
• Collaborating institutions 
Your information may be re-disclosed by the recipients described above, if they 
are not required by law to protect the privacy of the information. 
When will my authorization expire? 

 
19 
 
Your authorization for the use and/or disclosure of your health information will 
end on December 31, 2050 or when the research project ends, whichever is 
earlier. 
Will access to my medical record be limited during the study? 
To maintain the integrity of this research study, you may not have access to any 
health information developed as part of this study until it is completed. At that 
point, you would have access to such health information if it was used to make a 
medical or billing decision about you (e.g., if included in your official medical 
record). 
 
 
 
 
 
 

 
20 
 
FINANCIAL CONSIDERATIONS 
 
Payment 
Payment will be administered in the form of Amazon gift cards. 
Participants will be compensated a maximum of $220 for completion of patient- reported 
outcome (PRO) surveys. 
• 
Baseline, 6-month, and 12-month follow-up surveys will be worth $25 each, totaling 
$75. 
• 
Weekly questionnaires will be worth $5, and will be administered weekly over the course 
of the first 6 months of study participation and then monthly for the final 5 months of study 
participation (29 total surveys), totaling up to $145. 
Payments may only be made to U.S. citizens, legal resident aliens, and those who have a work 
eligible visa. You may need to provide your social security number to receive payment. 
Costs 
If you participate in this study, the study will pay for those services, supplies, procedures, and 
care associated with the study that are not a part of your routine medical care. However, 
there may be additional costs to you. These include basic expenses like transportation and the 
personal time it will take to come to the study visits. You and/or your health insurance must 
pay for services, supplies, procedures, and care that are required during this study for routine 
medical care. You will also be responsible for any co-payments and/or deductibles as 
required by your insurance. Participation in this study is not a substitute for health 
insurance. 
 
Sponsor 
Patient-Centered Outcomes Research Institute is providing financial support and/or material 
for this study. 
 
COMPENSATION for Research-Related Injury 
All forms of medical diagnosis and treatment - whether routine or experimental - involve some 
risk of injury. In spite of all precautions, you might develop medical complications from 
participating in this study. If such complications arise, the Protocol Director and the research 
study staff will assist you in obtaining appropriate medical treatment. In the event that you 
have an injury or illness that is directly caused by your participation in this study, 
reimbursement for all related costs of care first will be sought from your insurer, managed 
care plan, or other benefits program. You will be responsible for any associated co-
payments or deductibles as required by your insurance. 
If costs of care related to such an injury are not covered by your insurer, managed care plan 
or other benefits program, you may be responsible for these costs. If you are unable to pay 
for such costs, the Protocol Director will assist you in applying for supplemental benefits and 
explain how to apply for patient financial assistance from the hospital. 
You do not waive any liability rights for personal injury by completing this form. 
CONTACT INFORMATION 

 
21 
 
Questions, Concerns, or Complaints: If you have any questions, concerns or complaints about 
this research study, its procedures, risks and benefits, or alternative courses of treatment, you 
should ask the Protocol Director, Dr. Beth Darnall at (650) 721-2104.  You should also contact 
her at any time if you feel you have been hurt by being a part of this study. 
Independent Contact: If you are not satisfied with how this study is being conducted, or if you 
have any concerns, complaints, or general questions about the research or your rights as a 
participant, please contact the Stanford Institutional Review Board (IRB) to speak to someone 
independent of the research team at (650)-723-5244 or toll free at 1-866-680-2906. You can 
also write to the Stanford IRB, Stanford University, 1705 El Camino Real, Palo Alto, CA 94306. 
Appointment Contact: If you need to change your appointment, please contact the study team 
at (650) 724-9319. 
Alternate Contact: If you cannot reach the Protocol Director, please contact the Core Manager, 
Luzmercy Perez, at (650) 497-1095. 
EXPERIMENTAL SUBJECT'S BILL OF RIGHTS 
As a research participant you have the following rights. These rights include but are not 
limited to the participant's right to: 
• 
be informed of the nature and purpose of the experiment; 
• 
be given an explanation of the procedures to be followed in the medical experiment, and 
any drug or device to be utilized; 
• 
be given a description of any attendant discomforts and risks reasonably to be expected; 
• 
be given an explanation of any benefits to the subject reasonably to be expected, if 
applicable; 
• 
be given a disclosure of any appropriate alternatives, drugs or devices that might be 
advantageous to the subject, their relative risks and benefits; 
• 
be informed of the avenues of medical treatment, if any available to the subject after 
the experiment if complications should arise; 
• 
be given an opportunity to ask questions concerning the experiment or the procedures 
involved; 
• 
be instructed that consent to participate in the medical experiment may be withdrawn at 
any time and the subject may discontinue participation without prejudice; 
• 
be given a copy of the consent form; and 
• 
be given the opportunity to decide to consent or not to consent to a medical experiment 
without the intervention of any element of force, fraud, deceit, duress, coercion or 
undue influence on the subject's decision. 
If you agree to participate in this research, please verbally indicate this to the researcher. 
The extra copy of this consent form is for you to keep. 

 
22 
 
Yes, subject agrees to participate.
 
No, subject does not agree to participate.
 
Enter Name of Subject 
 
Enter Name of Person Obtaining Authorization 
 
Enter today’s date 
 
Are you participating in any other research studies? 
Yes
 
No
 
May we contact you about future studies that may be of interest to you? 
Yes
 
No
 
 
 

 
23 
 
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