Treating Chronic Pain in Buprenorphine Patients in Primary Care Settings
Phase: NA
Conditions: Opioid-Related Disorders
Sponsor: Boston University

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 1 of 32 
 
 
Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 
Protocol Version Number: 1.0 
Protocol Version Date: April 8th, 2025  
ClinicalTrials.gov number: NCT03698669 
Funding Mechanism:  NIDA 1R01DA045695 
Principal Investigator: Michael Stein 
 
Phone: 617 358 1956   
 
E-mail: mdstein@bu.edu 
 
 
 
Statistical Analysis Plan pages 23-25 
 
 
 
 
 
CONFIDENTIAL 
 
This document is confidential and the property of Boston University School of Public Health. No part 
of it may be transmitted, reproduced, published, or used by other persons without prior written 
authorization from the institution.  
© 2025 Trustees of Boston University. All rights reserved. 
 
 
 
 
 
 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 2 of 32 
TABLE OF CONTENTS 
1 List of Abbreviations .............................................................................................................. 3 
2 Protocol Summary .................................................................................................................. 3 
3 Background/Rationale & Purpose ....................................................................................... 4 
3.1 Background Information .............................................................................................. 4 
3.2 Rationale and Purpose ................................................................................................ 5 
4 Objectives ................................................................................................................................ 5 
4.1 Study Objectives ........................................................................................................... 5 
4.2 Study Outcome Measures ........................................................................................... 6 
4.2.1 
Primary Outcome Measures ......................................................................... 6 
4.2.2 
Secondary Outcome Measures ................................................................... 6 
4.2.3 
Exploratory Outcome Measures .................................................................. 6 
5 Study Design ........................................................................................................................... 6 
6 Potential Risks and Benefits ................................................................................................. 7 
6.1 Risks ............................................................................................................................... 7 
6.2 Potential Benefits .......................................................................................................... 9 
6.3 Analysis of Risks in Relation to Benefits ................................................................... 9 
7 Study Subject Selection ........................................................................................................ 9 
7.1 Subject Inclusion Criteria ............................................................................................. 9 
7.2 Subject Exclusion Criteria ........................................................................................... 9 
8 Study Intervention ................................................................................................................ 10 
9 Recruitment and Retention Procedures ........................................................................... 11 
9.1 Recruitment Procedures ............................................................................................ 11 
9.2 Retention Procedures ................................................................................................ 13 
10 Screening Procedures ......................................................................................................... 14 
11 Consent Procedures ............................................................................................................ 16 
12 Study Procedures ................................................................................................................. 17 
13 Assessment of Safety and Data Safety Monitoring Plan (DSMP) ................................ 20 
13.1 Definitions for Safety Assessment ........................................................................... 20 
13.2 Safety Review ............................................................................................................. 21 
13.3 Reporting Plans .......................................................................................................... 21 
13.4 Stopping Rules ............................................................................................................ 22 
14 Data Handling and Record Keeping .................................................................................. 22 
14.1 Confidentiality .............................................................................................................. 22 
14.2 Study Documentation, Source Data, and Case Report Forms (CRFs) ............. 23 
14.3 Study Records Retention .......................................................................................... 23 
15 Statistical Plan ...................................................................................................................... 23 
15.1 Study Hypotheses ...................................................................................................... 23 
15.2 Sample Size Determination ...................................................................................... 24 
15.3 Statistical Methods ..................................................................................................... 24 
16 Ethics/Protection of Human Subjects ................................................................................ 25 
17 Literature References .......................................................................................................... 25 
18 Appendix ................................................................................................................................ 27 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 3 of 32 
 
 
1 
List of Abbreviations 
 
 
Abbreviation 
Abbreviation definition 
TOPPS 
Treating Opioid Patients’ Pain and Sadness 
HE 
Health education 
BHS 
Behavioral Health Specialist 
OBAT 
Office-based addiction treatment 
BHS 
Behavioral Health Specialist 
RA 
Research Assistant 
CAM 
Complementary and Alternative Medicine 
OUD 
Opioid Use Disorder 
BA 
Behavioral Activation 
ACT 
Acceptance and Commitment Theory 
BPI 
Brief Pain Inventory 
VAS 
Visual Analog Scale 
PHQ-9 
Patient Health Questionnaire-9 
BADS 
Behavioral Activation for Depression Scale 
PASS 
Pain Anxiety Symptoms Scale 
SOP 
Standard Operating Procedure 
MSSI 
Modified Scale for Suicidal Ideation 
SCID 
Structured Clinical Interview for DSM 
SSTAR 
Stanley Street Treatment and Resources 
BMC 
Boston Medical Center 
BU 
Boston University 
BUP 
Buprenorphine 
EHR 
Electronic Health Records 
CDW 
Clinical Data Warehouse 
MOUD 
Medications for Opioid Use Disorder 
RW 
Risa Weisberg (PI) 
AE 
Adverse Event 
SAE 
Serious Adverse Event 
DSMB 
Data Safety and Monitoring Board 
IRB 
Institutional Review Board 
CRF 
Case Report Form 
MICE 
Multiple imputation by chained equation 
MAR 
Missing at random 
SEM 
Structural Equation Models 
ICH 
International Council for Harmonization 
 
2 
Protocol Summary 
 
Title: 
Treating Opioid Patients’ Pain and Sadness (TOPPS) 
Population: 
163 participants currently being treated with buprenorphine 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 4 of 32 
Intervention: 
Intervention: 12-week lifestyle psychoeducation about pain, 
depression, and opioid use; as well as values-based, behavioral 
activation to increase engagement in meaningful activities. 
Timing: 3-months  
Method: Randomized controlled trial 
Objectives: 
1) to determine whether the TOPPS intervention, compared to HE, 
results in less pain interference and pain severity over the 3-month 
treatment phase; 2) to determine whether TOPPS, compared to HE, 
results in less depressive symptoms over 3 months; 3) to determine 
whether TOPPS, compared to HE, results in sustained 
improvements in pain interferences, pain severity, depressive 
symptoms, and buprenorphine treatment retention (self-reported 
continuous treatment) over the 12 months of the study. 
Design/Methodology: 
163 participants who are currently being treated with 
buprenorphine and who endorse pain and depressive symptoms 
were randomized into the trial. Recruitment occurred from two 
primary care, office-based addiction treatment (OBAT) 
buprenorphine clinics, as well as through online advertisement. 
Following consent and the baseline interview, participants were 
randomized to one of two study arms: the TOPPS intervention or 
health education. The TOPPS intervention consists of 3 main 
components: 1) psychoeducation about pain, depression, opioid 
use, their interactions, and the role of avoidance; 2) coaching in 
how to be an informed, activated patient; and 3) values-based, 
behavioral activation, to increase engagement in meaningful 
activities. The intervention is a total of 6 phone-based sessions over 
12 weeks with a Behavioral Health Specialist (BHS). The control arm 
(health education) involves six sessions led by the same BHS. The 
first health education session is titled “What to Eat.” Participants 
then select five additional topics, one for each of the remaining 
sessions. Topics include, “What Not to Eat,” “Colds, Germs, and 
Flu,” “Preventing Cancer,” “Diabetes,” “Protecting your heart,” 
“Getting a Good Night’s Sleep,” “Complementary and Alternative 
Medicine (CAM),” “Caffeine,” and “Physical Activity.” Follow-up 
interviews are conducted by trained Research Assistants (RAs) at 1, 
2-, 3-, 6-, 9-, and 12-months (for participants enrolled prior to XX) 
post-enrollment. 
Total Study Duration: 
5 years 
Subject Participation Duration: 9-12 months 
 
3 
Background/Rationale & Purpose 
 
3.1 
Background Information 
An estimated 1.7 million adults used prescribed buprenorphine in 2019 [1]. >40% of those individuals 
have pain that interferes with daily activities and affects buprenorphine treatment outcomes [2]. 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 5 of 32 
Approximately 29–48% of individuals with substance use disorder are estimated to have depression 
[3,4]. Further, depression and pain often co-occur, with estimates of up to 72% of people with chronic 
pain meeting criteria for depression [5]. Though both pain and depression are common among patients 
with OUD (Opioid Use Disorder), these conditions often go unaddressed [6]. There are limited non-
pharmacological treatments available with the goal of improving pain outcomes. Furthermore, pain can 
interfere with effectiveness of antidepressants [7,8]. However, addressing pain or depression alone can 
be ineffective for patients suffering with both [9]. Studies have demonstrated that behavioral 
interventions are effective in patients with comorbid conditions, including substance use, depression, 
and chronic pain [10]. 
 
This study will be conducted in compliance with the protocol, applicable regulatory requirements, and 
policies and procedures of the Boston Medical Center and Boston University Medical Campus Human 
Research Protection Program and of the Institutional Review Board of Boston University Medical 
Campus 
 
3.2 
Rationale and Purpose  
 
We sought to develop and study an intervention to address this commonly occurring and often 
debilitating triad of conditions, pain, depression, and opioid use disorder. The TOPPS (Treating Opioid 
Use, Persistent Pain, and Sadness) intervention integrates and builds upon existing behavioral therapies 
for chronic pain and depression. Studies have shown that behavioral activation (BA) and values-based 
approaches such as Acceptance and Commitment Therapy (ACT) are efficacious treatments for chronic 
pain and depression [11,12]. Behavioral activation is frequently used in treatments for chronic pain and 
depression to counteract behavioral avoidance that interferes with daily functioning by increasing 
engagement with valued and enjoyable life activities [13]. BA therapy and ACT have demonstrated 
reductions in pain interference, stress, depression, and pain-related anxiety [14,15]. Similar to the ACT 
model, the TOPPS intervention supports participants in clarification of personal values, long and short-
term goal setting and behavioral activation in service of these values, and nonjudgmental acceptance of 
experiences as they pursue their goals. 
 
We have performed two promising pilot trials addressing pain depression together in vulnerable 
populations. The first involved persons living with HIV (N = 58) [16]. A more recent randomized trial 
(N =21) of TOPPS in persons receiving buprenorphine at two primary care sites showed promising 
decrements in pain interference with daily activities and pain severity when compared to the Health 
Education (HE) control condition. We thus planned to further evaluate the effectiveness of TOPPS in 
a fully powered trial. The TOPPS intervention includes psychoeducation about pain, depression, and 
opioid use; as well as values-based, behavioral activation to increase engagement in meaningful 
activities. The main study outcomes are reduced and sustained pain severity, pain interference, 
depressive systems, and buprenorphine treatment retention. 
 
4 
Objectives 
 
4.1 
Study Objectives 
 
The described study is a randomized clinical trial of the Treating Opioid Use, Persistent Pain, and 
Sadness (TOPPS) intervention compared to health education (HE) contact-control condition among 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 6 of 32 
persons receiving buprenorphine for opioid use disorder. The study objectives are as follows: 1) to 
determine whether the TOPPS intervention, compared to HE, results in less pain interference and pain 
severity over the 3-month treatment phase; 2) to determine whether TOPPS, compared to HE, results in 
less depressive symptoms over 3 months; 3) to determine whether TOPPS, compared to HE, results in 
sustained improvements in pain interferences, pain severity, depressive symptoms, and buprenorphine 
treatment retention (self-reported continuous treatment) over the 12 months of the study. Mechanisms 
by which TOPPS may reduce pain interference will also be examined, including 1) (increased) activities of 
engagement); 2) (decreased) avoidance of meaningful life activities; and 3) (decreased) fear of pain. 
4.2 
Study Outcome Measures 
 
 
4.2.1 Primary Outcome Measures 
 
The primary aim of this study is to test the hypothesis that participants randomized to the TOPPS 
intervention, compared to the Health Education condition will 1) have less pain interference and pain 
severity, as measured by the BPI (Brief Pain Inventory) and a Visual Analog Scale (VAS) at the end of the 
3-month treatment phase. 
4.2.2 Secondary Outcome Measures 
 
• 
Depression 
The PHQ-9 (Patient Health Questionnaire-9) will be used to measure depression severity and 
suicidality. It is a commonly used clinical interview that yields a depression severity score between 0 
and 27. 
• 
Buprenorphine treatment retention 
Buprenorphine treatment retention will be measured via chart review and participant self-report. 
4.2.3 Exploratory Outcome Measures 
 
We will examine potential mediators of change in our primary outcomes during the 3- month treatment 
period, decreased avoidance of life activities (BADS [Behavioral Activation for Depression Scale]), and 
decreased pain anxiety or fear of pain (PASS [Pain Anxiety Symptoms Scale]).  
, 
5 
Study Design 
 
Eligible participants will be adult men and women currently receiving buprenorphine. Participants will 
be randomized to either the TOPPS intervention or a health education intervention (HE). We will provide 
both interventions over three months and follow participants for a total of 9 months in order to observe 
both short-term and longer-term effects of the intervention. Participants are recruited from two primary 
care, office-based addiction treatment (OBAT) buprenorphine clinics in New England: a large, university-
affiliated, hospital-based clinic and a community health center’s buprenorphine program. In October 
2021, during the COVID-19 pandemic, recruitment was expanded to include targeted online 
advertisement primarily seen on social media sites, facilitated by BuildClinical LLC, a private software 
platform. After confirming study eligibility, the RA administers and documents informed consent within 
14 days of the participant screening eligible. Prior to March of 2020, informed consent procedures 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 7 of 32 
occurred in-person and took place on the same day as the participant’s baseline visit. All onsite research 
activities were paused at the onset of COVID-19 pandemic. Remote research activities resumed in 
October of 2020. At that time, the study team transitioned all research activities to be conducted over 
the phone and via mail. Informed consent is collected via an e-consent form. Upon signing of the 
informed consent, a subsequent baseline interview is scheduled. Eligible participants are administered 
the assessment and are randomized to one of the two study arms upon completion of the interview. 
Randomization is stratified on three factors: study enrollment site, disability status, and currently taking 
an antidepressant medication using randomly permuted blocks. There is a 1:1 random allocation of the 
intervention between the study groups. Follow up interviews are conducted by trained RAs at 1-, 2-, 3-, 
4-, 6-, 9-, and 12-months (for participants enrolled prior to October 2023) post-enrollment. 
 
6 
Potential Risks and Benefits 
 
6.1 
Risks 
 
There are four major areas of risk: 
• 
Confidentiality and loss of privacy. Study personnel will be collecting considerable information 
about the study participants. This may create some distress and could cause social and 
psychological risk if released inappropriately. This risk is a serious one but we believe that it is 
highly unlikely. We have extensive experience taking measures appropriate to safeguarding 
confidential information. 
• 
Increased distress due to assessment or intervention procedures. It is possible that some 
patients will experience increased intrapersonal or interpersonal psychological distress as a 
result of participating in assessment or intervention. Psychological risks of TOPPS may include 
discomfort with attention to unpleasant thoughts, feelings or body sensations. Some individual 
may experience an initial increase in undesirable feelings with increased attention to them. 
However, participants are self-guided and are encouraged to set their own limitations. In 
addition, the intervention is specifically geared towards dealing with such discomfort. In the vast 
majority of cases, we believe that any increased distress experienced will be mild and transitory 
in nature. 
• 
Ineffective intervention. It is possible that some participants will not experience improvements 
in pain or depression-related outcomes OR will experience clinical deterioration or suicidality 
• 
Potential coercion. It is possible that individuals may feel coerced into participating. This risk is a 
serious one but we believe that it is highly unlikely given informed consent processes and the 
ease with which one may withdraw from the study. 
 
The following steps will be taken in order to protect and/or mitigate risk: 
• 
Interview: Before conducting research assessments, participants will be assured of 
confidentiality and told that they have the right to terminate the interview or to refuse to 
answer specific questions. Some interview questions may be considered sensitive and may 
cause emotional distress. It will be critical to make clear to participants that they can terminate 
the interview at any time for any reason. The interviewer will be trained to be sensitive to signs 
of participant discomfort and to suggest breaks where it seems appropriate. 
• 
Intervention: Participation in the intervention may result in an initial increase in undesirable 
feelings. Interventionists will be trained to be aware of this possibility and how to help the 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 8 of 32 
participant manage these feelings. In addition, participants are instructed to pace themselves 
through the intervention, and are encouraged to set their own limitations. Furthermore, the 
intervention is specifically geared towards dealing with such discomfort. 
• 
Confidentiality: Loss of confidentiality is another possible risk. All information will be referenced 
to a participant identification number and will be sequestered in locked file cabinets in a locked 
office. The participant’s ID number can be connected to the participant’s name only through a 
single master file, password-protected, accessible only to senior research staff. We will protect 
all data files with passwords and lock any paper-based data collection instruments in cabinets. 
Risk of loss of confidentiality in conducting follow-ups will be avoided by having our interviewers 
never indicate to anyone other than the participant the purpose of the contact, unless the 
participant has given prior informed consent to do so. 
• 
Risk of ineffective intervention: The risk of possible ineffective intervention will be minimized 
by the fact that study participants will continue with their current medication or other 
treatment for chronic pain and for depression. Study participants may choose to discontinue 
study participation at any time if they wish to enroll in non-study psychotherapy during the 
intervention phase 
 
Given that all participants will have risk factors for suicidality (i.e., chronic pain and elevated depressive 
symptoms), some participants may experience suicide ideation or behavior in the course of study 
participation. Significant risk for suicide will be defined by PHQ-9 total score of 18 or greater, a score of 
greater than 0 on question 9 of PHQ-9 (both indicating suicide ideation or intent or behavior), OR the 
report of a desire or intent to hurt oneself to study staff. All staff members will be trained by Dr. Stein 
on the study’s Suicide Ideation Protocol. Details on the procedural steps will be included in the study’s 
Standard Operating Procedures (SOP), a copy of which all Research Assistants have with them at all 
times. The Suicide Ideation SOP details key warning signs and/or language of a participant with possible 
suicidal or homicidal thoughts and procedures for next steps. If a staff member encounters an individual 
who endorses suicide or homicide ideation, they will use the MSSI (Modified Scale for Suicidal Ideation) 
to ask a series of follow up questions to determine if a participant has a plan to hurt themselves or 
others, if they have tried to do so in the past, and if they have access to a specific method of self-harm. 
Following this brief discussion, the research member will immediately call a senior staff member to 
review the participant’s responses and determine if immediate action is necessary. Each site will have at 
least two licensed clinicians identified to assist with study participants who endorse harming themselves 
or others. This individual will be called and/or paged and will reach out to the participant immediately 
for evaluation. When a clinician is asked to conduct an immediate evaluation, he or she will conduct a 
suicide risk assessment. The clinician will determine whether it is necessary to take immediate action to 
prevent the participant from causing harm to him/herself. If the participant is not in immediate danger 
of hurting him or herself, we will take the following actions. First, we will inform the patient about 
procedures for contacting emergency services should they find themselves at risk for self-harm. Second, 
with the patient’s permission, we will contact their primary care physician or other clinician to inform 
them of the suicidality. We will urge the patient to make an appointment with that provider to discuss 
treatment options. Third, if the patient consents, we will speak with one of their family members to 
ensure that he/ she is aware of the seriousness of the patient’s symptoms and the agreed-upon 
treatment plan. We will provide treatment referrals if the patient wishes. Regardless of outcome, 
suicide assessments are always documented in writing.  
  

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 9 of 32 
If a participant endorses suicide or homicide ideation over the phone, all procedures will remain the 
same, however, we first ask the participant where they are in case emergency services need to be called 
to their location. The research staff will keep the participant on the phone and conference in the study 
clinician to conduct the suicide risk assessment. Additionally, all participants will be given a brochure at 
enrollment with information about local resources for mental health services and suicide prevention. 
 
6.2 
Potential Benefits 
 
From a societal standpoint, this research endeavor could lead to the incorporation of a theoretically-
driven and effective behavioral health treatment for patients with pain and depression into OUD care. 
This would be the first large-scale study of behavioral health treatment for chronic pain in people with 
OUD. We believe that this treatment will lead to improved pain, depression, and OUD outcomes. The 
risks of suicide or homicide are inherent in this patient population. All participants may acquire an 
increased awareness of their connections between pain and depression, and how these connections 
may relate to their OUD care plan. Participants assigned to the Life Goals intervention may further 
benefit by developing pain and mood management skills. Participants assigned to the HE intervention 
may benefit by increasing their knowledge of general health issues. Given that the risks of participation 
are fairly low, the risks to participants are judged to be acceptable relative to the anticipated benefits. 
 
6.3 
Analysis of Risks in Relation to Benefits 
 
The risks to participants are judged to be acceptable relative to the anticipated benefits. By participating 
in the clinical research project, participants may benefit from the intervention that they will receive. The 
potential benefits to others in the future and to the scientific community, and thus to society, are 
considerable, and the risk-benefit ratio is deemed favorable. 
 
7 
Study Subject Selection 
 
7.1 
Subject Inclusion Criteria 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
• 
Between 18 and 65 years of age 
• 
Have chronic pain, defined as pain duration for at least three months with a mean score of 4 or 
higher on the BPI Pain Interference Scale 
• 
Pain severity of 4 or higher on a Numeric Rating Scale (0-10) indication “worst pain in the last 
week” 
• 
If using an antidepressant, the dose must be stable for the previous 2 months 
• 
Has received buprenorphine from current primary care provider for at least the last month 
• 
Score of at least 4 on the PHQ-8 during prescreen and score of at least 4 on PHQ-9 during 
screening 
• 
Gives informed consent to participate in the study 
 
7.2 
Subject Exclusion Criteria 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
• 
Expected surgery in the next 3 months 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 10 of 32 
• 
Pain thought to be due to cancer 
• 
Greater than or equal to 10 days of cocaine/crack/methamphetamine use in the past month 
• 
Current mania or past year psychosis as determined via SCID (Strutured Clinical Interview for 
DSM) Modules A and B/C 
• 
Lifetime diagnosis of schizophrenia or other chronic psychotic condition as determined by the 
study PI 
• 
Planning to stop using buprenorphine in the next 6 months 
• 
Headache/migraine is the only reported site of pain 
• 
Pregnancy or planned pregnancy in the next 6 months 
• 
Greater than 8 homeless nights in the past month 
• 
Suicide ideation or behavior requiring immediate attention 
• 
Not able to complete interviews in English 
• 
Unable to provide names and contact information for at least two verifiable locator persons 
who will know where to find them in the future 
• 
Greater than or equal to 45 days without a phone in the past 3 months/no reliable access to 
phone 
• 
REMOTE ONLY: Does not have internet access or mailing address 
• 
IF PASSIVE RECRUITMENT: Cannot confirm active buprenorphine prescription 
 
8 
Study Intervention 
 
The TOPPS study will compare two groups:  TOPPS intervention (Intervention condition) and Health 
Education (Control Condition). The intervention will last three months. All participants will participate in 
6 intervention sessions with a trained Behavioral Health Specialist (BHS). For both TOPPS and HE 
participants, Session 1 will be a one-on-one conversation between the BHS and the participant. Session 
1 can be completed in the same day as the baseline assessment or it can be completed on a different 
day either by phone or in-person. Sessions 2-6 may be conducted over the phone for both intervention 
groups but can also occur in-person, if necessary. Intervention sessions 2-6 will occur in order, the 
interventionists will not move on to the next session until the previous one has been completed. 
Participants will schedule intervention sessions separately with study staff based on BHS availability. 
  
 
TOPPS: 
TOPPS consists of three main components: (1) psychoeducation about pain, depression, opioid use, their 
interactions, and the maintaining role of avoidance; (2) coaching in being an informed, activated patient 
(based in part on the chronic care model and on approaches to self-management of chronic illness); and 
(3) behavioral activation to increase engagement in meaningful activities. Life Goals Behavioral Health 
Specialists (BHS) do not directly treat substance misuse/abuse, but they do assess substance use and 
support all efforts to attain or maintain sobriety as part of buprenorphine care and retention; these may 
become part of the patient’s life goals. Life Goals BHSs describe their goal as helping patients to engage 
more in their life as a patient with chronic illness by reducing avoidance and increasing achievement of 
life goals. Consistent with an effort to engage patients, Life Goals will aim to involve an initial face-to-
face meeting followed by regular phone meetings. In preliminary research, patients found this format to 
be convenient. The initial meeting includes the patient and the BHS. After each Life Goals session, with 
patient permission, the BHS mails or emails a copy of the clinical note to the patient. This note increases 
the contact between patient and BHS, serves as a reminder to patients about their goals, and 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 11 of 32 
encourages the patient to be informed and activate in their own healthcare. Additionally, each 
participant is provided with a workbook that reviews the key elements of each treatment session and 
provides exercises for at-home practice of skills. Session 1 will last for 45 minutes. All following sessions 
will last for a maximum of 30 minutes. Sessions 1-6 will occur over the phone or in-person, if necessary. 
 
Health Education: 
The initial meeting includes the patient and the BHS to discuss nutrition. For the next 5 sessions, they 
choose from a menu of topics, including: a second session on nutrition; germs, colds and the flu; 
preventing cancer; diabetes; protecting your heart; getting a good night’s sleep; complementary and 
alternative medicine; caffeine, or physical activity. This control condition was accepted by our 
participants in preliminary studies; it does not directly target functional impairment, and participants do 
not set tailored goals relating to their own values. Session 1 will last for 45 minutes. All following 
sessions will last for a maximum of 30 minutes. Sessions 1-6 will occur over the phone or in-person, if 
necessary. 
 
9 
Recruitment and Retention Procedures 
 
9.1 
Recruitment Procedures 
 
Participants will be recruited from two sites: Boston Medical Center Office Based Addiction Treatment 
(OBAT) program and Stanley Street Treatment and Resources (SSTAR) in Fall River, Massachusetts, as 
well as through advertising and passive recruitment. 
Potential participants recruited through OBAT and SSTAR will be recruited through letters mailed or 
emailed by a member of the research team, flyers given by clinic staff during the potential participant's 
scheduled medical appointment in the OBAT program or through SSTAR, or following RA introduction by 
a member of OBAT or SSTAR clinic staff. Potential participants may opt out from the study before eligibility 
screening occurs. Patients who do not opt out will be contacted (by phone or in person) by a member of 
the research team. Potential participants may also reach out to study staff directly based on response to 
advertisements or following passive recruitment (e.g. word-of-mouth, current participant referral, or 
flyer). 
 
On initial approach, the RA will introduce the study, review the screening consent form and obtain verbal 
consent prior to administering the eligibility screening questionnaire. Recruitment data will be collected 
through REDCap. Patients who meet the initial eligibility requirements will be asked to schedule a 
telephone call or to meet in-person with a member of the research team to conduct the informed consent 
procedures, administer the post-written consent eligibility screener (to confirm eligibility and to link their 
screening data to identifiers), administer additional post-written consent screening measures (namely the 
PHQ-9 and the SCID Module A and Module BC, and confirm buprenorphine prescription for those 
recruited via advertisements or passive recruitment) and complete the baseline assessment, and if 
eligible, complete intervention procedures. All of these procedures may take place on the same day but 
are not required to occur on one day. 
1. EHR/CDW Data Pull: Patient lists will be generated by the Electronic Health Record (EHR) data pull or 
Clinical Data Warehouse (CDW) and may include either: 
1) Patients who, (1) currently receive buprenorphine, and (2) have an encounter with the OBAT 
clinic within the specified date range; 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 12 of 32 
2) Or may include patients who, (1) currently receive buprenorphine, (2) have an encounter with 
the OBAT clinic within the specified date range, and (3) have at least one of the following listed in 
their medical record: pain diagnosis, depression diagnosis, or a prescription for an antidepressant. 
Providers will be provided with the generate list of their patients to be screened either in person or via a 
note in the EHR, and will have the chance to remove patients from the list that they feel should not be 
approached. To minimize undue burden on potential participants and providers, research staff may access 
the electronic medical record to confirm eligibility by CDW criteria prior to adding potential participants 
to the provider lists. Research staff will mail or email individualized letters to potential participants using 
“opt-out” language, such that the potential participant must call the study phone number to avoid being 
contacted by research staff. This letter will be signed by and sent on behalf of  the Medical Director or 
head nurse of the medication-assisted treatment program (in the case of SSTAR) or by the Medical 
Director (in the case of OBAT). 
2. In-person Recruitment: Participants who have received an opt-out letter but cannot be reached by 
phone may be approached by study staff during their clinic appointment. Study staff will request approval 
from the potential participant’s provider before approaching the participant. Study staff will provide the 
participant with information about the study and if the participant is interested and has time, complete 
screening procedures. 
Participants may also be identified by clinic staff and may either be given a brochure with information 
about the study or be directly introduced to study staff (warm hand-off). 
3. Passive Recruitment: Study staff may hang flyers advertising the study and study contact information. 
Study staff may advertise the study (e.g. via Google Ads, Reddit, Craigslist, StudyFinder, Facebook, Twitter, 
Suboxone-related websites/online forums, and paper flyers) or participants may be referred to the study 
by other means (e.g. enrolled participant referral). We have expanded passive recruitment via the service 
of BuildClinical. BuildClinical is a data-driven software platform that helps academic researchers recruit 
participants for research studies more efficiently using social media, software, and machine learning. They 
utilize study-specific advertisements to engage participants on digital platforms such as Facebook, Google, 
WebMD, etc., and redirect them to a study-specific landing page should they click it. Interested 
participants who reach out to study staff for more information (either by phone or in-person) will be 
screened for eligibility.  RAs also have the option to send potentially eligible participants a private 
scheduling link using Microsoft Bookings for Me,a HIPAA-compliant Microsoft-based scheduling tool that 
integrates directly with BU (Boston University) Outlook emails and calendars. When potentially eligible 
participants fill out a pre-screening form from BuildClinical, RAs will reach out via text or email with the 
15-minute phone screen scheduling link, and the participants will have the option to self-schedule a time 
on the research assistant’s calendar. Participants would only be able to see the times the RA is available; 
no other details of the RA’s calendar will be visible. RAs could also send this link to potentially eligible 
participants who filled out the BuildClinical screening form and we have not yet been able to get in contact 
with (before the implementation of Bookings With Me). Participants recruited via passive recruitment 
who report being on BUP (buprenorphine) will be asked to provide confirmation that they are actively 
receiving a buprenorphine prescription during screening measures after full consent. Following initial 
screening measures, if eligible and interested, potential participants will be informed they will need to 
provide proof of active BUP prescription at their next study appointment. Participants who report being 
on BUP during screening will provide confirmation through self-report. This will be confirmed through 
objective data. Verification of BUP can occur through the following: 
1. Participant providing a pill bottle or image thereof that confirms the BUP prescription belongs 
to them. Study staff will review the pill bottle/image of pill bottle but will not retain any data from 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 13 of 32 
the bottle; study staff will only report Y/N was buprenorphine prescription confirmed and the 
avenue by which it was confirmed. 
2. Participant providing written script or image thereof that confirms the BUP prescription belongs 
to them. Study staff will review the script/image of script but will not retain any data from the 
script; study staff will only report Y/N was buprenorphine prescription confirmed and the avenue 
by which it was confirmed. 
3. Participant providing description of injectable BUP receipt which can include: date, provider 
name, and dosage amount. Study staff will review responses with study PI(s) and Research 
Manager to confirm participant eligibility. This information will not be saved with the participant’s 
screening data; study staff will only report Y/N was buprenorphine prescription confirmed and 
the avenue by which it was confirmed. 
4. Verbal or written communication from MOUD (medications for opioid use disorder) prescriber 
or opioid treatment program after participant has signed 42 CFR Part 2 compliant ROI. Written 
communication will not be retained; study staff will only report Y/N was buprenorphine 
prescription confirmed and the avenue by which it was confirmed. 
RA will simply mark, BUP prescription confirmed, Y/N and the route of confirmation in the screening form. 
The RA will not retain data beyond confirmation and route of confirmation. 
If remote, participants will be asked to send a photo of options 1-2 via secure email or text message. For 
the transfer of sensitive BUP data, study staff will always attempt to request this data via BU's secure 
email service, DataMotion. Study staff will send an encrypted email to participants via DataMotion during 
screening measures after full consent. Participants will be instructed to create a username and password 
for DataMotion and respond with a photo of options 1 or 2. If the participant requests to send this photo 
via unencrypted email or text message, study staff will remind participants of the risks of sending sensitive 
data via unencrypted communication methods, as written in the Locator Form and make note in the 
Locator Form notes section of the participant’s final choice in method of data transfer. If the participant 
chooses to send BUP confirmation data via unencrypted communication methods, study staff will advise 
participants to delete the message/image from their electronic devices. Once the BUP prescription is 
confirmed, this photo will be immediately deleted and wiped from memory by study staff.  
If in person, participants will be asked to bring options 1 or 2 to their study appointment. 
If receiving injectable BUP participants should be prepared to answer a series of questions regarding their 
injectable BUP, the answers of which will not be recorded by study staff. 
If participants recruited via passive recruitment cannot confirm active BUP prescription, they will not be 
able to be enrolled in the study. 
 
 
9.2 
Retention Procedures 
 
Maintaining a high follow-up rate will be essential to the successful completion of this study. 
Participants will take part in the following research assessments: baseline, 1-, 2- 3-, 6,  9-, and 12-month. 
Within each assessment period, there is an interview that is estimated to last between 60 and 120 
minutes. To enhance participant retention, participants will receive compensation for each individual 
interview. Participants will receive compensation following assessment completion. The amount of 
compensation for assessment completion is based on the length of the assessment (larger 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 14 of 32 
compensation for baseline and 3 month) and will increase incrementally throughout the course of the 
study to aid in study retention. The maximum total participants can earn for completing study 
interviews is $370 or $430 (for those who complete a 12-month interview). 
 
To assist in maintaining high follow-up rates for study assessments, study staff will contact participants 
by phone, email, and text message to communicate about assessment reminders, scheduling, re-
scheduling, etc.  
 
Study staff will also mail out letters to hard-to-reach participants to remind them of their upcoming 
intervention sessions, if needed. 
 
10 Screening Procedures 
 
Potential participants will be recruited through letters mailed by a member of the research team, by 
flyers given by clinic staff during the potential participant's scheduled medical appointment in the OBAT 
program or through SSTAR, or following RA introduction by a member of OBAT or SSTAR clinic staff. 
Potential participants may also reach out to study staff directly based on response to advertisements or 
following passive recruitment (eg. word-of-mouth, current participant referral, or flyer). Potential 
participants may opt out from the study before eligibility screening occurs. Patients who do not opt out 
will be contacted (by phone or in person) by a member of the research team (see Recruitment section). 
 
1. EHR/CDW Data Pull: Patient lists will be generated by Electronic Health Record or Clinical Data 
Warehouse and and may include either: 
Patients who (1) currently receive buprenorphine, and (2) have an encounter with the OBAT clinic within 
the specified date range; Or may include patients who (1) currently receive buprenorphine, (2) have an 
encounter with the OBAT clinic within the specified date range, and (3) have at least one of the 
following listed in their medical record: pain diagnosis, depression diagnosis, or a prescription for an 
antidepressant. 
Providers will be provided with the generate list of their patients to be screened either in person or via a 
note in the EHR, and will have the chance to remove patients from the list that they feel should not be 
approached. To minimize undue burden on potential participants and providers, research staff may 
access the electronic medical record to confirm eligibility by CDW criteria prior to adding potential 
participants to the provider lists. Research staff will mail or email individualized letters to potential 
participants using “opt-out” language, such that the potential participant must call the study phone 
number to avoid being contacted by research staff. This letter will be signed by and sent on behalf of the 
patient's provider (in the case of SSTAR) or by the Medical Director (in the case of OBAT). 
 
2. In-person Recruitment: Participants who have received an opt-out letter but cannot be reached by 
phone may be approached by study staff during their clinic appointment. Study staff will request 
approval from the potential participant’s provider before approaching the participant. Study staff will 
provide the participant with information about the study and if the participant is interested and has 
time, complete screening procedures. 
 
Participants may also be identified by clinic staff and may either be given a brochure with information 
about the study or be directly introduced to study staff (warm hand-off). 
 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 15 of 32 
3. Passive Recruitment: Study staff may hang flyers advertising the study and study contact information. 
Study staff may advertise the study (e.g. via Google Ads, Reddit, Craigslist, StudyFinder, Facebook, 
Twitter, Suboxone-related websites/online forums, and paper flyers) or participants may be referred to 
the study by other means (e.g. enrolled participant referral). The screening process for participants 
recruited via BuildClinical will be identical to those screened via passive recruitment (i.e., those who 
reach out to the study team upon seeing an advertisement on Craigslist), with the addition of the 
BuildClinical landing page and pre-screening form (BuildClinical Pre-Screening Questionnaire). Upon 
clicking on the advertisement, potential participants will be brought to the TOPPS study landing page 
built by BuildClinical, which provides basic information on the study and acts as a Brief Screening 
Agreement in this way. If the potential participant is interested in the study and would like to see if they 
are eligible, they would then click the link to the Pre-Screening Questionnaire. Research Assessors will 
be able to review participant’s responses to the questionnaire and reach out to them if they are eligible 
based on the questions, which represent a subset of the questions on the full screener. From there, RAs 
would contact the potential participant, administer the approved Brief Screening Agreement, obtain 
verbal consent, and complete the TOPPS Screening Questionnaire, as usual. 
 
Interested participants who reach out to study staff for more information (either by phone or in-person) 
will be screened for eligibility. Participants recruited via passive recruitment who report being on BUP 
will be asked to provide confirmation that they are actively receiving a BUP prescription during 
screening measures after full consent. Following initial screening measures, if eligible and interested, 
potential participants will be informed they will need to provide proof of active BUP prescription at their 
next study appointment. Participants who report being on BUP during screening will provide 
confirmation through self-report. This will be confirmed through objective data. 
Verification of BUP can occur through the following: 
•Participant providing a pill bottle or image thereof that confirms the BUP prescription belongs to them. 
Study staff will review the pill bottle/image of pill bottle but will not retain any data from the bottle; 
study staff will only report Y/N was buprenorphine prescription confirmed and the avenue by which it 
was confirmed. 
•Participant providing written script or image thereof that confirms the BUP prescription belongs to 
them. Study staff will review the script/image of script but will not retain any data from the script; study 
staff will only report Y/N was buprenorphine prescription confirmed and the avenue by which it was 
confirmed. 
•Participant providing description of injectable BUP receipt which can include: date, provider name, and 
dosage amount. Study staff will review responses with study PI(s) and Research Manager to confirm 
participant eligibility. This information will not be saved with the participant’s screening data; study staff 
will only report Y/N was buprenorphine prescription confirmed and the avenue by which it was 
confirmed. 
•Verbal or written communication from MOUD prescriber or opioid treatment program after participant 
has signed 42 CFR Part 2 compliant ROI. Written communication will not be retained; study staff will 
only report Y/N was buprenorphine prescription confirmed and the avenue by which it was confirmed. 
RA will simply mark, BUP prescription confirmed, Y/N and the route of confirmation in the screening 
form. The RA will not retain data beyond confirmation and route of confirmation. 
 
If remote, participants will be asked to send a photo of options 1 or 2 via secure email or text message. 
For the transfer of sensitive BUP data, study staff will always attempt to request this data via BU's 
secure email service, DataMotion. Study staff will send an encrypted email to participants via 
DataMotion during screening measures after full consent. Participants will be instructed to create a 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 16 of 32 
username and password for DataMotion and respond with a photo of options 1-2. If the participant 
requests to send this photo via unencrypted email or text message, study staff will remind participants 
of the risks of sending sensitive data via unencrypted communication methods, as written in the Locator 
Form and make note in the Locator Form notes section of the participant’s final choice in method of 
data transfer. If the participant chooses to send BUP confirmation data via unencrypted communication 
methods, study staff will advise participants to delete the message/image from their electronic devices. 
Once confirmed, this photo will be immediately deleted and wiped from memory by study staff. 
 
If in person, participants will be asked to bring options 1 or 2 to their study appointment. 
 
If receiving injectable BUP participants should be prepared to answer a series of questions regarding 
their injectable BUP, the answers of which will not be recorded by study staff. 
 
Participants can also choose to sign a release form to allow study staff to confirm BUP prescription with 
their current provider. If remote, this will be signed via REDCap. 
 
If participants recruited via passive recruitment cannot confirm active BUP prescription, they will not be 
able to be enrolled in the study. 
 
Patients who do not opt out will be contacted (by phone or in person) by a member of the research 
team. On initial approach, the RA will introduce the study, review the screening consent form and obtain 
verbal consent prior to administering the eligibility screening questionnaire. Screening data will be 
collected through REDCap. We will de-identify the data for all participants who are screened out of the 
study. Data for participants who remain enrolled in the study will also be de-identified. Patients who 
meet the initial eligibility requirements will be asked to schedule a telephone call or to meet in-person 
with a member of the research team to conduct the informed consent procedures, administer the 
eligibility screener (to confirm eligibility and to link their screening data to identifiers), administer 
additional screening measures (namely the PHQ-9 and the SCID Module A and Module B/C, and confirm 
BUP prescription for those recruited via advertisements or passive recruitment) and complete the 
baseline assessment, and if eligible, complete intervention procedures. 
 
11 Consent Procedures  
 
If the individual is willing to participate, the research assistant will administer informed consent (Written 
Consent Form) for study participation. The consent process will take place in a private space either at 
Boston University Medical Campus or SSTAR, or may occur electronically or over the phone with a 
witness. A Written Consent Form will be given to potential participants prior to consent either in person 
or by mail, secure email, or REDCap, if remote. The potential participant will be given time to read the 
study consent form and fact sheet prior to consent. Participants will not be consented to the study if 
they have not yet received a consent form from study staff. The forms will be reviewed with the 
potential participant either in person or by an audio only phone call, Zoom teleconferencing software, or 
BU Teams communications platform. There will be time for the potential participant to ask questions 
prior to consenting to study participation. The potential participant may postpone consent if they would 
like more time to consider study participation prior to consent. 
 
The informed consent form explains the purpose of the research, the nature and duration of the study, 
that the study is voluntary, that a participant may withdraw consent at any time during the study, 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 17 of 32 
potential disadvantages of participation, alternatives to participation, and procedures for safeguarding 
confidentiality. To ensure informed consent comprehension RAs will utilize the Informed Consent 
Checklist and Teach Back. Participants will be given a copy of their signed consent when in person or 
sent an electronic PDF of their signed consent via REDCap or secure email, if possible. 
 
If in person, participants will provide consent by signing a physical consent form. If the participant is a 
limited or non-reader, an impartial witness will also be present during consent and will sign confirming 
the consent process was completed appropriately. 
 
If remote, consent may occur electronically via REDCap - this can occur via the e-consent method or the 
remote signature consent method. Participants who provide consent using the e-consent method will be 
directed to sign the consent form electronically via REDCap. Participants who provide consent using the 
remote signature method will direct a witness taking part in the consent discussion to sign on behalf of 
the participant. If a participant is a limited- or non-reader the witness will be impartial and will NOT be a 
member of the study team. The witness will be present for the entire consent discussion. For 
participants who are NOT limited- and non-readers but who are unable to engage in e-consent, the 
witness can be a member of the study team since there is no requirement for an impartial witness in this 
study but may also be an impartial witness if a study team member is unavailable. The witness will be 
present for the end of the consent discussion when the signature is applied to the consent form but can 
also be present for the entire consent discussion, if they so choose. The participant will be reminded to 
apply their signature or mark on their copy of the consent form. 
 
If a participant is consented via the remote signature consent process, meaning they cannot 
electronically sign the consent form, the witness signature will suffice as signature via proxy. If the 
participant completes an assessment in person in the future, staff will make every effort to have the 
participant physically sign the witness signed consent form. The form signed would be the same consent 
form version they were originally consented with using the remote signature consent process. The 
participant will be instructed to sign with the date of original consent and a note to file will be created 
that indicates the signature was formally applied at an in-person visit. If staff are unable to get a 
participant signature during an in-person assessment for any reason, consent remains intact.  
 
For participants who are limited- and non-readers but do have access to internet, we will attempt to 
obtain an electronic signature via REDCap if there is someone present with them who can read and help 
them sign (e.g., spouse). If no such person is available, then we will utilize the remote signature consent 
process as described above. 
 
12 Study Procedures 
 
See the Appendix for the schedule of events.  
 
Baseline and Follow-Up Assessments: 
The baseline visit with take place at BMC (Boston Medical Center) or SSTAR if possible, but may also be 
conducted by telephone. At consent/baseline, research staff will collect participants’ contact 
information, including phone number(s), mailing address, and e-mail address if applicable. Staff will also 
collect the phone numbers for two alternate contacts that they may call if unable to reach the 
participant. Research staff will keep in regular contact with participants by phone or by text message, 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 18 of 32 
and participants will be encouraged to contact the study team if they change their contact information. 
If participants report that they plan to enter a temporary residence, shelter, or facility, they will be 
asked to fill out a form authorizing the facility to release their admission status and/or contact 
information to study staff. If remote, this form can be sent electronically (REDCap/Docusign). If this is 
not possible, we will wait to complete this form until assessments can occur in person. If a participant 
becomes incarcerated during study participation, research staff will not complete assessments with 
them while incarcerated but will monitor release date to re-engage the participant upon release. 
Participants will be compensated for each assessment and FitBit Inspire return and we will attempt to 
contact participants for all assessments regardless of whether they remain in the assigned treatment 
(see Table 1). Compensation can include Visa® gift cards or electronic gift cards. We may also cover local 
transportation costs and offer offsite or phone assessments to increase convenience for participants.  
 
The baseline interview is administered by trained RAs and takes approximately two hours to complete. A 
list of assessment measures is included in the Appendix. Participants are mailed or emailed assessment 
scales prior to the scheduled call. Participants’ eligibility is reassessed at this time, and if they are found 
to be no longer eligible, they are compensated and thanked for their time. Eligible participants are 
administered the assessment and are randomized upon completion of the interview. 
 
Assessments will be conducted in-person and over the phone. Baseline assessments will take a 
maximum of one hour to complete (expected 45 minutes). Follow-up assessments will take one half 
hour to complete. Assessments will be directly entered into REDCap when possible, however paper 
versions will be available if an assessment is conducted off-site. Participants will receive compensation 
following assessment completion. The amount of compensation for assessment completion is based on 
the length of the assessment (larger compensation for baseline and 3 month) and will increase 
incrementally throughout the course of the study to aid in study retention. 
 
FitBit Inspire Tracking: 
All study participants will receive a FitBit Inspire to collect the number of steps taken per day. 
Participants will not be given access to the FitBit web-based or smartphone applications. Participants 
will be asked to wear the FitBit continuously for 7 days after baseline and return the FitBit either in 
person or via pre-paid envelopes. Participants will be compensated for returning their FitBit Inspire. 
 
Intervention Sessions: 
TOPPS 
The TOPPS intervention consists of 3 main components: 1) psychoeducation about pain, depression, 
opioid use, their interactions, and the role of avoidance; 2) coaching in how to be an informed, activated 
patient; and 3) values-based, behavioral activation, to increase engagement in meaningful activities. 
Throughout the intervention, three core messages are discussed with participants: 1) Everyone 
experiences sadness and pain. Just because something hurts, it doesn’t mean it’s dangerous; 2) It is 
natural to want to be comfortable. Nearly everyone wants to avoid sadness and pain; and 3) Sometimes 
working towards important goals is worth it, even if it temporarily increases pain or discomfort. 
Participants are informed that the primary goal of this intervention is not take away all of their pain, but 
rather to help them ‘live the life they want, as comfortably as possible”. 
 
There are a total of six phone-based sessions. The first two sessions last approximately 50 min each; the 
remaining four sessions are approximately 30 min in duration. Session 1 is focused on a) rapport 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 19 of 32 
building; b) validating the participant’s experience with both physical and emotional pain; c) 
psychoeducation about the differences between acute and chronic pain, the relationship between pain 
and depression, and the role of avoidance in maintaining a cycle of pain, depression, and substance use; 
d) values clarification; and e) beginning to set long-term goals in service of the participant’s values. 
During values clarification, interventionists work with participants to help them identify the things that 
matter most to them (e.g., family, helping others, community, friendship, health, etc.) and to 
understand the ways in which their aspirations have been altered or unfulfilled due to their pain and 
substance use. Long-term goals are set collaboratively, with the interventionist assisting the participant  
to identify things they would like to achieve in life, in service of their values, and which are manageable 
with whatever restrictions their pain and substance use history may have caused. 
During session 2, identification of long-term goals is completed. Interventionists then teach SMART goal 
setting, helping patients to make Specific, Measurable, Achievable, Relevant, and Time-bound short-
term goals as the steps needed to take to get to achieve their long-term goals. For example, the 
participant sets a goal to spend 30 min, on Monday and Wednesday evening, using his laptop to 
research potential volunteer opportunities in his area. He also set goals to text one of his old friends to 
say hello and that he felt badly he been out of touch for so long and to begin taking short, 10-min walks, 
3 days a week. 
Sessions three – six are focused on review of previous short-term goal progress, setting new short-term 
goals, and establishing goal-setting skills to be used by the participant independently in the future. Time-
based pacing, a technique common to behavioral treatments for chronic pain in which participants 
identify the amount of time they can perform a task without an increase in pain and then plan to break 
the activity into time blocked segments of this duration, is also taught. The goal of time-based pacing is 
to help ensure that participants don’t take on too much physical activity all at once in pursuing their 
short-term goals leading to increases in pain and feeling unable to continue working towards their goals. 
Skills to be a more active and informed participant in care of their chronic conditions (pain, substance 
use) are also taught, such as making a list of questions for their healthcare providers keeping a calendar 
with all their appointments listed, etc. 
The intervention is delivered by Behavioral Health Specialists (BHSs), who have backgrounds in mental 
health counseling (i.e., clinical psychology graduate students, MSWs, and PhD psychologists). Upon 
randomization, each participant assigned to the intervention is assigned a specific BHS with whom they 
meet for the duration of the intervention. The first session is scheduled to take place within two weeks 
of the baseline assessment. All sessions are audio-recorded. At each session, the BHS administers the 
Patient Health Questionnaire-2 (PHQ-2), a pain questionnaire, and buprenorphine adherence questions.  
Sessions 1 and 2, and sessions 2 and 3 are ideally scheduled to take place within one week of each 
other. Remaining sessions are scheduled approximately two weeks apart. To allow for flexibility, 
participants have 3 months to complete all six sessions. 
 
Control Condition- Health Education 
Participants randomized to the control HE condition are offered six sessions led by the BHSs. As with 
TOPPS, each participant is assigned one BHS who delivers all their sessions. The same pool of BHSs 
provides TOPPS and HE. TOPPS research assistants have also been trained to deliver HE if BHS caseload 
capacity is low. RAs do not administer assessments to any participants to whom they deliver HE. 
Delivery, timing, and duration of the HE sessions are identical to the TOPPS intervention condition. The 
first health education session is titled “What to Eat.” Participants then select five additional topics, one 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 20 of 32 
for each of the remaining sessions. Topics include, “What Not to Eat,” “Colds, Germs, and Flu,” 
“Preventing Cancer,” “Diabetes,” “Protecting your heart,” “Getting a Good Night’s Sleep,” 
“Complementary and Alternative Medicine (CAM),” “Caffeine,” and “Physical Activity.” At each session, 
the Behavioral Health Specialists also administer the same mood, pain, and buprenorphine adherence 
questionnaires as in the TOPPS condition. 
 
Treatment Fidelity and Training 
Fidelity checklists are used for each session (e.g., rapport building, completion of planned agendas, 
content), including measurement of potential contamination across interventions. Investigator (RW, Risa 
Weisberg) and one or more additional PhD-level psychologists rate 50% of the initial sessions of BHSs in 
the training phase and then 10% of all other sessions. Fidelity ratings are used to measure adherence to 
the interventions and to provide feedback and education to BHSs and promote discussion in biweekly 
supervision sessions. 
Prior to beginning the first intervention case, behavioral health specialists participate in training that 
involved the following elements: a) individually reviewing the intervention manuals; b) three hours of 
training with one of the study investigators (RW), in which the rationale and background science for the 
interventions are discussed, the session structure and primary goals of each session are reviewed, and 
the main therapeutic content of each intervention are reviewed with examples and/or role-playing 
provided on how to deliver these elements; c) listening to recorded example cases of each intervention; 
and d) a follow-up meeting with RW to answer any questions raised when reviewing the example cases. 
 
Follow Up Assessments 
Follow up interviews are conducted by trained RAs at 1-, 2-, 3-, 4-, 6-,9-, and 12-months post-
enrollment. All sections of the assessment are interviewer-administered and entered directly into 
REDCap. Participants are compensated up to $430 in gift cards throughout the study. Participants 
receive compensation at the end of each baseline or follow-up assessment. 
 
13 Assessment of Safety and Data Safety Monitoring Plan (DSMP) 
 
13.1 Definitions for Safety Assessment 
 
The following definitions will be used in the assessment of safety: 
 
Adverse Event (AE) is any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the subject’s participation in the research, whether or not considered 
related to the subject’s participation in the research. 
 
Serious Adverse Event (SAE) is any adverse event that  
(1) results in death; 
(2) is life-threatening; 
(3) results in inpatient hospitalization or prolongation of existing hospitalization; 
(4) results in a persistent or significant disability/incapacity; 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 21 of 32 
(5) results in a congenital anomaly/birth defect; or 
(6) based upon appropriate medical judgment, may jeopardize the subject's health and may require 
medical or surgical intervention to prevent one of the other outcomes listed in this definition 
(examples of such events include allergic bronchospasm requiring intensive treatment in the 
emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse).  
 
Life-threatening means that the event places the subject at immediate risk of death from the event as it 
occurred.  
 
Unanticipated Problem is defined as an event, experience or outcome that meets all three of the 
following criteria:  
• 
is unexpected; AND 
• 
is related or possibly related to participation in the research; AND 
• 
suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.  
 
Possibly related means there is a reasonable possibility that the incident, experience, or outcome may 
have been caused by the procedures involved in the research 
 
Unexpected means the nature, severity, or frequency of the event is not consistent with either: 
• 
the known or foreseeable risk of adverse events associated with the procedures involved in the 
research that are described in (a) the protocol–related documents, such as the IRB-approved 
research protocol (Institutional Review Board), any applicable investigator brochure, and the 
current IRB-approved informed consent document, and (b) other relevant sources of information, 
such as product labeling and package inserts; or 
• 
the expected natural progression of any underlying disease, disorder, or condition of the 
subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the 
adverse event. 
 
13.2 Safety Review 
 
Both the risks listed in Section 4.1 and unknown risks will be monitored as follows: Adverse events and 
serious adverse events, including but not limited to psychological stress or discomfort form research 
interviews, and loss of confidentiality, will be reported by study staff (e.g., research assistants, project 
manager, PIs, etc) and monitored by the principal investigator. SAEs will be evaluated within 48 hours of 
the study staff and team becoming aware of the event for severity, seriousness, and relatedness. We 
have procedures and reminders in place for study staff to notify the principal investigator when an AE or 
SAE is reported. Additionally, we will send a yearly report to our Data Safety Monitoring Board (DSMB) 
who will monitor and review AEs and SAEs. The DSMB will review rates of adverse events to determine 
any changes in participant risk, recruitment and retention, and participant drop out, and will make 
appropriate recommendations for changes in protocol, which will be submitted to the Boston University 
Medical Campus IRB for review. A brief report will be generated yearly for the study record and 
forwarded to the Boston University Medical Campus IRB.  
 
 
13.3 Reporting Plans 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 22 of 32 
 
    
The Principal Investigator at BMC/BU Medical Campus will report Unanticipated Problems, safety 
monitors’ reports, and Adverse Events to the BMC/BU Medical Center IRB in accordance with IRB 
policies: 
 
• 
Unanticipated Problems occurring at BMC/BU Medical Campus will be reported to the BMC/BU 
Medical Campus IRB within 7 days of the investigator learning of the event. 
• 
Adverse Events (including Serious Adverse Events) will be reported in summary at the time of 
continuing review, along with a statement that the pattern of adverse events, in total, does not 
suggest that the research places subjects or others at a greater risk of harm than was previously 
known. 
• 
Reports from safety monitors with recommended changes will be reported to the IRB within 7 
days of the investigator receiving the report.  
• 
Reports from safety monitors with no recommended changes will be reported to the IRB at the 
time of continuing review.  
 
13.4 Stopping Rules 
 
The study has no pre-defined stopping rules.  
 
14 Data Handling and Record Keeping 
 
14.1 Confidentiality 
All data will be collected for research purposes and all records will be stored in locked filing cabinets or 
password protected computers accessible only to research staff. Research data will be collected and 
stored using subject IDs rather than participant names or other direct identifiers such as medical record 
number. Any paper copies will be kept in locked offices. Electronic files containing any identifiable 
information (such as the study key) will be password protected and only research staff will have access 
to the password. The study key will be kept separate from the study data (assessments and audio 
recordings). Files containing audio-recordings of participants will be password protected as well. 
Study data collected by research study staff during research interviews in private locations. Study data 
collected by research study staff includes baseline and follow-up interview data. All research interview 
data will be entered into REDCap, managed by BEDAC. REDCap is a secure, web application designed to 
support data capture for research studies, providing user-friendly web-based case report forms, real-
time data entry validation (e.g. for data types and range checks), audit trails, and data export 
mechanism to common statistical packages (SPSS, SAS, Stata, R/S-Plus). The system was developed by a 
multi-institutional consortium and was initiated at Vanderbilt University. The REDCap is hosted on a 
computer network exploitation -based server. Network transmissions (data entry, survey submission, 
web browsing, etc.) in REDCap are protected via Secure Sockets Layer (SSL) encryption. Access to 
REDCap can be restricted at different levels (e.g., research assistant, PI, and Co-Investigators). Exported 
data from REDCap will be stored on the Boston University Medical Campus’ secure password-protected 
server.  
 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 23 of 32 
Audio-recordings of intervention sessions with participants will be uploaded and stored on a secure, 
HIPAA compliant server (e.g., DropBox, Box.com, SharePoint, etc). A study ID will be used to identify the 
recordings. They are not connected with the primary study database in any way. 
 
14.2 Study Documentation, Source Data, and Case Report Forms (CRFs) 
 
Data sources in the study include pre-screening data collected via BuildClinical, the phone screening 
data, baseline, 1, 2-, 3-, 5-, 6-, 9- and 12-month assessment data to be collected via phone or in-person 
and input into REDCap by study staff, medical record data, and, audio-recordings.  
 
Screening information collected via BuildClinical will be housed securely in BuildClinical’s online 
platform. Screening information on potentially eligible participants collected by BU study staff will be 
housed securely in REDCap. 
 
The phone screen and study baseline and follow-up interview data will be collected verbally from the 
participant to study staff over the phone, and directly entered by research staff into REDCap case report 
forms, and stored electronically in REDcap. Information collected during the phone screening is 
collected to determine eligibility for the study. Research interviews will collect information on 
demographic variables, health and medical status, symptoms of anxiety and depression, pain, recent 
medical appointments, current medications, knowledge of opioids, pain treatments, physical activity, 
substance use, psychosocial functioning, experience of discrimination, satisfaction with the intervention, 
and more. Data collected at the follow up time points are to understand change over time, especially 
after the intervention period.  
RAs conducted medical chart reviews from participants who were recruited from the two primary care, 
office-based addiction treatment (OBAT) buprenorphine clinics in New England to collect data on 
buprenorphine retention at 6- and 12-months post-enrollment.  
Corrections on data collection forms: If any entry error has been made to hardcopy data collection 
forms, to correct such an error, a single straight line will be drawn through the incorrect entry and the 
correct data will be entered above it. All such changes will be initialed and dated.  There will be no 
erasures or white-out on CRFs.  For clarification of illegible or uncertain entries, the clarification will be 
printed above the item, then initialed and dated. 
 
14.3 Study Records Retention 
 
All study records (e.g., informed consent, REDCap survey records, intervention session recordings, etc.) 
from this trial will be retained for a minimum of seven years after the study is completed per Boston 
Medical Center and Boston University requirements. Data stored in REDCap will be managed and 
retained by study staff. Hard copy documents will be stored in locked filing cabinets. After the seven 
years of required data retention, the study PI will determine when the information can be destroyed. 
 
15 Statistical Plan 
 
15.1 Study Hypotheses 
 
1. Participants in the TOPPS intervention, compared to Health Education, will report less pain 
interference and pain severity over the 3-month treatment phase. 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 24 of 32 
2. Participants in the TOPPS intervention, compared to Health Education, will report fewer 
depressive symptoms over the 3-month treatment phase. 
3. The TOPPS intervention, compared to HE, will result in sustained improvements in pain 
interference, pain severity, depressive symptoms and buprenorphine treatment retention over 
the study period. 
Examining mechanisms by which TOPPS may reduce pain interference. Proposed mechanisms include: 1) 
(increased) steps per day (as a measure of general physical activity level); 2) (increased) activities 
engagement; 3) (decreased) avoidance of meaningful life activities; and 4) (decreased) fear of pain. 
 
15.2 Sample Size Determination 
 
We plan to recruit 125 subjects to each study condition. Based on an attrition rate of 20% we anticipate 
having approximately 100 participants per condition available for analysis. Our primary power 
calculations are based on Aim 1. Based on the literature [17-19], we determined that a minimally 
significant difference between treatment groups on outcomes would be a standardized mean difference 
(SMD) of at least 0.4 at 3 months. Assuming α/2 = 0.05, we need 99 subjects per arm to detect an SMD 
of 0.4 with 1-β = 0.8. Thus, the proposed design has sufficient power to detect small-moderate effects 
for Aims 1 and 2. 
15.3 Statistical Methods 
 
We will present descriptive statistics. Random effects logistic regression will be used to determine if 
treatment condition, demographic characteristics, or baseline outcome measures predict study attrition. 
Any variables that significantly (p < .10) predict study attrition will be included in multiple imputation 
models and as covariates in multivariate models testing the effects of intervention. Graphical methods 
will be used to evaluate the distributions of outcome variables, examine model residuals, describe 
change in outcomes over time, and guide the specification generalized linear mixed models testing 
intervention effects. A 2-tailed probability of Type I error < 0.05 will be used for all null hypothesis tests. 
Missing data due to participant attrition and item non-response is inevitable. We will conduct intent-to-
treat analysis using multiple imputation by chained equation (MICE) to generate fully populated data 
sets [20]. More specifically we will use the mi impute and mi estimate facilities in Stata 17 to generate 
and analyze the fully populated data files [21]. The number of imputed data sets will be determined by 
using the how many imputations procedure [22]. MICE is a flexible tool that allows imputing values for 
outcomes with a range of distributions (e.g., continuous, dichotomous, count, etc.). MICE assume data 
are missing at random (MAR) (e.g., missing is random conditional on variables in the imputation model). 
Variables used in the imputation models will include treatment assignment, all observed instances of the 
outcome being imputed, and any additional baseline variables found to significantly (p < .10) predict 
subject attrition using mixed-effects logistic regression. Including baseline predictors of attrition 
supports the MAR assumption. 
The BPI, the VAS pain severity scales (worst and average in last week), and the PHQ-9 will be 
administered at baseline and at all follow-up assessments. The effect of intervention on pain 
interference (BPI-I), pain severity, and depressive symptoms during the 3-month treatment phase will be 
evaluated in a generalized linear mixed model framework using the fully populated data sets generated 
by MICE. Models will include baseline pain and PHQ-9 depression measures as covariates. All available 
panel data will be included in the model to support the efficiency of estimation. Time specific estimates 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 25 of 32 
of treatment effects (e.g., the effect of treatment at 3-months) can be obtained by including the 
treatment by categorical (indicator variables) time interaction term. We plan to use the contrast and 
mimrgns post-estimation commands in Stata to recover relevant parameter estimates and test statistics. 
More specifically, a Wald χ2-test will be used to test the simple main effect of treatment at end of 
treatment. Additionally, we will generate graphs plotting the estimated average marginal means to 
facilitate substantive interpretation of results. Parallel methods will be used to evaluate the sustained 
effect of treatment post end-of-treatment (4-, 6-, 9-, and 12- months). Wald χ2-tests will again be used 
to test the simple main effects of treatment at post end-of-treatment assessments to determine if 
intervention effects are sustained over time. 
The Cox proportional hazards model will be used to test the hypothesis that participants randomized to 
TOPPS will have higher buprenorphine treatment retention than persons randomized to HE. The 
outcome will be operationalized as self-reported continuous treatment since the prior interview at the 
time point assessed.  
We will use Mplus 7 [23] to specify and estimate structural equation models (SEM) testing the 
hypothesis that decreased avoidance, and fear of pain mediate the relationship between intervention 
and pain interference and severity. 
Additional baseline covariates will include ratings of pain severity, pain interference, and depression. As 
recommended by MacKinnon et al. [24], the statistical significance of the indirect effect will be assessed 
using bias-corrected bootstrapped standard errors. Significant indirect effects are consistent with the 
hypothesis that change in the purported mechanisms mediates the effect of intervention on outcome. 
16 Ethics/Protection of Human Subjects 
 
This study is to be conducted according to applicable US federal regulations and institutional policies 
(which are based in federal regulations, guidance, and ICH (International Council for Harmonization) 
Good Clinical Practice guidelines). 
 
This protocol and any amendments will be submitted to the Boston Medical Center and Boston 
University Medical Campus IRB / Name of IRB of record for formal approval of the study conduct. The 
decision of the IRB concerning the conduct of the study will be made in writing to the investigator. A 
copy of the initial IRB approval letter will be provided to the sponsor before commencement of this 
study.  
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study. The 
consent form will be submitted with the protocol for review and approval by the IRB. The consent of a 
subject, using the IRB-approved consent form, must be obtained before that subject is submitted to any 
study procedure. Consent will be documented as required by the IRB.   
 
17 Literature References 
 
[1] 
B. Han, C.M. Jones, E.B. Einstein, W.M. Compton, Trends in and Characteristics of 
Buprenorphine Misuse Among Adults in the US, JAMA Network Open 4 (2021) e2129409. 
https://doi.org/10.1001/jamanetworkopen.2021.29409. 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 26 of 32 
[2] 
M.D. Stein, D.S. Herman, G.L. Bailey, J. Straus, B.J. Anderson, L.A. Uebelacker, R.B. Weisberg, 
Chronic pain and depression among primary care patients treated with buprenorphine, J Gen Intern 
Med 30 (2015) 935–941. https://doi.org/10.1007/s11606-015-3212-y. 
[3] 
T. Santo, G. Campbell, N. Gisev, D. Martino-Burke, J. Wilson, S. Colledge-Frisby, B. Clark, L.T. 
Tran, L. Degenhardt, Prevalence of mental disorders among people with opioid use disorder: A 
systematic review and meta-analysis, Drug Alcohol Depend 238 (2022) 109551. 
https://doi.org/10.1016/j.drugalcdep.2022.109551. 
[4] 
B.J. Morasco, J.P. Duckart, S.K. Dobscha, Adherence to clinical guidelines for opioid therapy for 
chronic pain in patients with substance use disorder, J Gen Intern Med 26 (2011) 965–971. 
https://doi.org/10.1007/s11606-011-1734-5. 
[5] 
H. Poole, S. White, C. Blake, P. Murphy, R. Bramwell, Depression in chronic pain patients: 
prevalence and measurement, Pain Pract 9 (2009) 173–180. https://doi.org/10.1111/j.1533-
2500.2009.00274.x. 
[6] 
K.M. Berg, J.H. Arnsten, G. Sacajiu, A. Karasz, Providers’ Experiences Treating Chronic Pain 
Among Opioid-Dependent Drug Users, J Gen Intern Med 24 (2009) 482–488. 
https://doi.org/10.1007/s11606-009-0908-x. 
[7] 
J.I. Russell, P.J. Mease, T.R. Smith, D.K. Kajdasz, M.M. Wohlreich, M.J. Detke, D.J. Walker, A.S. 
Chappell, L.M. Arnold, Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or 
without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-
controlled, fixed-dose trial, Pain 136 (2008) 432–444. https://doi.org/10.1016/j.pain.2008.02.024. 
[8] 
T.W. Meeks, L.B. Dunn, D.S. Kim, S. Golshan, D.D. Sewell, J.H. Atkinson, B.D. Lebowitz, Chronic 
pain and depression among geriatric psychiatry inpatients, Int J Geriatr Psychiatry 23 (2008) 637–642. 
https://doi.org/10.1002/gps.1954. 
[9] 
S.R. Currie, D.C. Hodgins, A. Crabtree, J. Jacobi, S. Armstrong, Outcome from integrated pain 
management treatment for recovering substance abusers, J Pain 4 (2003) 91–100. 
https://doi.org/10.1054/jpai.2003.17. 
[10] 
K. Barrett, Y.-P. Chang, Behavioral Interventions Targeting Chronic Pain, Depression, and 
Substance Use Disorder in Primary Care, J Nurs Scholarsh 48 (2016) 345–353. 
https://doi.org/10.1111/jnu.12213. 
[11] 
J.W. Kanter, R.C. Manos, W.M. Bowe, D.E. Baruch, A.M. Busch, L.C. Rusch, What is behavioral 
activation? A review of the empirical literature, Clin Psychol Rev 30 (2010) 608–620. 
https://doi.org/10.1016/j.cpr.2010.04.001. 
[12] 
D.A. Richards, D. Ekers, D. McMillan, R.S. Taylor, S. Byford, F.C. Warren, B. Barrett, P.A. Farrand, 
S. Gilbody, W. Kuyken, H. O’Mahen, E.R. Watkins, K.A. Wright, S.D. Hollon, N. Reed, S. Rhodes, E. 
Fletcher, K. Finning, Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy 
for Depression (COBRA): a randomised, controlled, non-inferiority trial, Lancet 388 (2016) 871–880. 
https://doi.org/10.1016/S0140-6736(16)31140-0. 
[13] 
E.H. Kim, T.B. Crouch, B.O. Olatunji, Adaptation of behavioral activation in the treatment of 
chronic pain, Psychotherapy 54 (2017) 237–244. https://doi.org/10.1037/pst0000112. 
[14] 
J.P. Sanabria-Mazo, A. Colomer-Carbonell, X. Borràs, J.R. Castaño-Asins, L.M. McCracken, J. 
Montero-Marin, A. Pérez-Aranda, S. Edo, A. Sanz, A. Feliu-Soler, J.V. Luciano, Efficacy of 
Videoconference Group Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy 
for Depression (BATD) for Chronic Low Back Pain (CLBP) Plus Comorbid Depressive Symptoms: A 
Randomized Controlled Trial (IMPACT Study), The Journal of Pain (2023) S1526590023004005. 
https://doi.org/10.1016/j.jpain.2023.04.008. 
[15] 
J.L. Wetherell, N. Afari, T. Rutledge, J.T. Sorrell, J.A. Stoddard, A.J. Petkus, B.C. Solomon, D.H. 
Lehman, L. Liu, A.J. Lang, J. Hampton Atkinson, A randomized, controlled trial of acceptance and 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 27 of 32 
commitment therapy and cognitive-behavioral therapy for chronic pain, PAIN 152 (2011) 2098–2107. 
https://doi.org/10.1016/j.pain.2011.05.016. 
[16] 
L.A. Uebelacker, R.B. Weisberg, D.S. Herman, G.L. Bailey, M.M. Pinkston-Camp, S.L. Garnaat, 
M.D. Stein, Pilot Randomized Trial of Collaborative Behavioral Treatment for Chronic Pain and 
Depression in Persons Living with HIV/AIDS, AIDS Behav 20 (2016) 1675–1681. 
https://doi.org/10.1007/s10461-016-1397-7. 
 [17] 
National Institute for Health and Clinical Excellence, Clinical Guideline 23 (amended): 
Depression: Management of depression in primary and secondary care., National Institute for Health 
and Clinical Excellence, London, UK, 2007. 
[18] 
U. Hegerl, R. Mergl, The clinical significance of antidepressant treatment effects cannot be 
derived from placebo-verum response differences, J Psychopharmacol 24 (2010) 445–448. 
https://doi.org/10.1177/0269881109106930. 
[19] 
R.H. Dworkin, D.C. Turk, K.W. Wyrwich, D. Beaton, C.S. Cleeland, J.T. Farrar, J.A. 
Haythornthwaite, M.P. Jensen, R.D. Kerns, D.N. Ader, N. Brandenburg, L.B. Burke, D. Cella, J. Chandler, P. 
Cowan, R. Dimitrova, R. Dionne, S. Hertz, A.R. Jadad, N.P. Katz, H. Kehlet, L.D. Kramer, D.C. Manning, C. 
McCormick, M.P. McDermott, H.J. McQuay, S. Patel, L. Porter, S. Quessy, B.A. Rappaport, C. Rauschkolb, 
D.A. Revicki, M. Rothman, K.E. Schmader, B.R. Stacey, J.W. Stauffer, T. von Stein, R.E. White, J. Witter, S. 
Zavisic, Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: 
IMMPACT recommendations, J Pain 9 (2008) 105–121. https://doi.org/10.1016/j.jpain.2007.09.005. 
[20] 
M.J. Azur, E.A. Stuart, C. Frangakis, P.J. Leaf, Multiple imputation by chained equations: what is 
it and how does it work?, Int J Methods Psych Res 20 (2011) 40–49. https://doi.org/10.1002/mpr.329. 
[21] 
Stata Statistical Software, (2020). 
[22] 
P.T. Von Hippel, How Many Imputations Do You Need? A Two-stage Calculation Using a 
Quadratic Rule, Sociological Methods & Research 49 (2020) 699–718. 
https://doi.org/10.1177/0049124117747303. 
[23] 
L.K. Muthén, B.O. Muthén, Mplus User’s Guide, Seventh Edition, Muthén & Muthén, Los 
Angeles, CA, 1998. 
[24] 
D.P. MacKinnon, C.M. Lockwood, J. Williams, Confidence Limits for the Indirect Effect: 
Distribution of the Product and Resampling Methods, Multivariate Behav Res 39 (2004) 99. 
https://doi.org/10.1207/s15327906mbr3901_4. 
 
18 Appendix 
 
Schedule of Events  
Table 1. Schedule of Study Measures 
 
 
 
 
Follow-Up Assessment (Months) 
Measure 
Description 
Baseline Sessions 
1 
2 
3 
4 
6 
9 
12 
Sociodemographics 
Baseline 
Demographic 
questions, 
including age 
and 
incarceration 
history 
X 
 
 
 
 
 
 
 
 
Sociodemographics 
Follow-up 
Demographic 
questions, 
X 
 
X 
X 
X 
X 
X 
X 
X 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 28 of 32 
including places 
slept  
PHQ-91 
Measure of 
severity of 
depression 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BPI2 
Ratings of pain 
severity and 
interference 
X 
X 
X 
X 
X 
X 
x 
X 
X 
Pain Experiences3  
Time ratings of 
least severe pain 
X 
 
X 
X 
X 
X 
X 
X 
X 
BADS4  
Measure of 
behavioral 
activation of 
depression 
X 
 
X 
X 
X 
X 
X 
X 
X 
Buprenorphine and 
Pain - Baseline 
Measures of 
how 
buprenorphine 
helps with pain  
X 
 
 
 
 
 
 
 
 
GAD-75  
Measure of 
severity of 
anxiety  
X 
 
X 
X 
X 
X 
X 
X 
X 
TSR – Baseline6  
Compiling a list 
of medical 
appointments in 
the past 3 
months 
X 
 
 
 
 
 
 
 
 
TSR- Follow-Up6  
Compiling a list 
of medical 
appointments 
since last 
follow-up 
 
 
X 
X 
X 
X 
X 
X 
X 
TRAQ7  
Compiling a list 
of current 
medications  
X 
 
X 
X 
X 
X 
X 
X 
X 
Knowledge 
Questionnaire 
Assess patient 
knowledge of 
opioids 
X 
 
 
 
 
 
 
 
 
Pain Treatment 
Questionnaire8  
Endorsements of 
pain treatments 
X 
 
X 
X 
X 
X 
X 
X 
X 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 29 of 32 
used and ranking 
of their 
helpfulness  
IPAQ9  
Measure of 
physical 
activities in the 
past 7 days  
X 
 
X 
X 
X 
X 
X 
X 
X 
CPAQ10  
Assess 
acceptance of 
chronic pain  
X 
 
X 
X 
X 
X 
X 
X 
X 
PASS11  
Assess anxiety 
around pain 
X 
 
X 
X 
X 
X 
X 
X 
X 
PROMIS Global 
Health12  
Assess general 
domains of 
health and 
functions 
X 
 
X 
X 
X 
X 
X 
X 
X 
ASI – Baseline13  
Compile lifetime 
use of drugs and 
in the last 30 
days  
X 
 
 
 
 
 
 
 
 
ASI – Follow-up13  Compile use of 
drugs in the last 
30 days  
 
 
X 
X 
X 
X 
X 
X 
X 
Nicotine14  
Determine 
cigarette use and 
how often 
X 
 
 
 
 
 
 
 
 
DIS15  
Assessing Pain 
sensitivity  
X 
 
 
 
X 
 
X 
 
X 
Perceived Control 
Scale16  
Assessing sense 
of agency  
X 
 
 
 
X 
 
X 
 
X 
CPV-I17  
Determine 
values and 
success living 
according to 
those values 
X 
 
X 
X 
X 
X 
X 
X 
X 
Experience of 
Discrimination18  
Determine 
history of 
discrimination 
based on identity  
X 
 
 
 
 
 
 
 
 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 30 of 32 
Buprenorphine and 
Pain – Follow-up 
Assessing 
buprenorphine 
effectiveness 
with pain 
 
 
X 
X 
X 
X 
X 
X 
X 
Patient Global 
Impression of 
Change19  
Assess impacts 
of study on their 
pain and sadness 
 
 
X 
X 
X 
X 
X 
X 
X 
CSQ-820  
Assess 
satisfaction with 
the intervention 
in general 
 
 
 
 
X 
 
 
 
 
Patient 
Satisfaction21  
Assess 
satisfaction with 
specific aspects 
of the 
intervention 
 
 
 
 
X 
 
 
 
 
CEQ22 
Assess 
effectiveness of 
intervention 
after Session 1  
X 
 
 
 
 
 
 
 
 
Buprenorphine 
Adherence 
Assess current 
use of 
buprenorphine  
 
X 
 
 
 
 
 
 
 
1Patient Health Questionnaire-9 and -2 (PHQ-9, -2), 2Brief Pain Inventory (BPI), 3Pain 
Experience, 4Behavioral Activation for Depression Scale (BADS), 7GAD-7 (General Anxiety 
Disorder-7), 6Treatment Services Review (TSR), 7Transition Readiness Assessment 
Questionnaire (TRAQ), 8Pain Treatment Questionnaire, 9International Physical Activity 
Questionnaire (IPAQ)  , 10Chronic Pain Acceptance Questionnaire (CPAQ), 11Pain Anxiety 
Symptom Scale (PASS), 12Patient-Recorded Outcomes Measure Information System (PROMIS) 
Global Health, 13Addiction Severity Index (ASI), 14The Fagerström Test for Nicotine 
Dependence (Nicotine), 15Discomfort Intolerance Scale (DIS), 16Perceived Control Scale, 
17Chronic Pain Value Inventory (CPV-I), 18Experience of Discrimination, 19Patient Global 
Impression of Change, 20Client Satisfaction Questionnaire-8 (CSQ-8), 21Patient Satisfaction, 
22Credibility/Expectancy Questionnaire (CEQ)  
 
Table 2.  Intervention Topics by Session 
Session 
Number 
Week 
Number 
Contents 
Session 1 
Week 1 
• Introduction to TOPPS intervention 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 31 of 32 
• Elicit history of participants’ opioid use, 
recovery/buprenorphine treatment, pain, and 
depression, including an understanding of 
the participants’ current and planned 
buprenorphine treatment and any medical 
treatment for pain and/or depression  
• Explain the role of avoidance 
• Values clarification 
• Begin to explore participants’ long-term 
goals 
• Describe treatment and enhance motivation 
for the intervention 
• Homework: participant is asked to continue 
identification of long-term goals and think 
about what is important in their life 
Session 2 
Week 2 
• Psychoeducation about core messages of 
TOPPS 
• Pain and discomfort (e.g., sad feelings) are 
not dangerous in and of themselves 
• Avoidance is a natural response to 
emotional and physical pain 
• Pain and discomfort may be necessary to 
achieve important life goals 
• Complete long-term goal setting.  
• Teach SMART goals 
• Set short-term, SMART goals 
corresponding to long- term goals, for the 
next 2 weeks. 
Session 3 
Week 4 
• Review core messages 
• Review of short-term goals set at session 2 
and any barriers to meeting these goals 
• Discussion of time-based pacing 
• Setting a short-term goal to apply pacing to 
physically active task (e.g., walking, 
cleaning) 
• Setting of short-term goals corresponding to 
long-term goals for the following 2 weeks 
Session 4 
Week 6 
• Review core messages 
• Discussion of short-term goals set at 
previous meeting, and barriers to meeting 
these goals 
• Introduce concept of disease self-
management and being an activated, 
informed patient. This includes discussions 

Treating Opioid Patients’ Pain and Sadness (TOPPS) 
 Version 1.0, April 8th, 2025 
 
Page 32 of 32 
of medication adherence, communication 
with provider, and making choices about 
one’s own care. 
• Setting of a goal that will help the 
participant to be more active in the 
management of their chronic conditions 
• Setting of short-term goals corresponding to 
long-term goals for the following 2 weeks 
Session 5 
Week 8 
• Discussion of short-term goals set at 
previous meeting, and barriers to meeting 
these goals 
• Setting of short-term goals corresponding to 
long-term goals for the following 2 weeks 
• Identification of accomplishments made 
during the course of the intervention 
• Planning for the participant to continue this 
work on their own 
Session 6 
Week 11 
• Discussion of short-term goals set at 
previous meeting, and barriers to meeting 
these goals 
• Plan for how participant will continue to 
work towards long-term goals after end of 
therapy