Study Design
This single-center two-group randomized (1:1 ratio) trial will examine the feasibility, acceptability, and preliminary efficacy of IPGT on patients with chronic pain who are at risk for opioid misuse. The study protocol and procedures were approved by the University of Pittsburgh Institutional Review Board for human subject’s research. The ClinicalTrials.gov Identifier is NCT03648177. Patients who meet all study criteria for inclusion will be required to provide written informed consent. Following consent and enrollment, participants will complete a baseline assessment and then will be randomly assigned to the Treatment as Usual (TAU) or IPGT study conditions. Outcome variables will be collected at pre and post-treatment (6 weeks), in addition to a follow up (9 weeks) assessment. Figure. 1 depicts the study’s CONSORT diagram.
The study's hypotheses include:
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Feasibility: There will be no difference in the frequency of attrition across experimental group and control group (IPGT vs. TAU) in addition to successful delivery of all intervention components to 75% of IPGT treatment recipients
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Acceptability: IPGT will demonstrate high levels of intervention satisfaction and retention (75%) at study completion as determined through the completion of a Patient Satisfaction Questionnaire, which will include a 16 item 5-point Likert scale.
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3. a) Preliminary efficacy for knowledge on opioid medication, opioid overdose, and opioid overdose response: Chronic pain patients who are at risk for opioid misuse who receive IPGT when compared with those who receive TAU will demonstrate significantly greater improvements in knowledge related to opioid medication, opioid overdose, and overdose response.
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3. b) Preliminary efficacy for opioid misuse: Chronic pain patients who are at risk for opioid misuse who receive IPGT when compared with those who receive TAU will demonstrate significant reduction in opioid misuse.
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3. c) Preliminary efficacy for pain severity, pain interference, and pain catastrophizing: Chronic pain patients who are at risk for opioid misuse who receive IPGT when compared with those who receive TAU will demonstrate significantly greater improvements in pain severity, pain interference, and pain catastrophizing.
Study Setting
The study will be conducted at an interdisciplinary outpatient pain clinic, affiliated with an academic medical center in Southwestern Pennsylvania. This clinic provides comprehensive research, clinical, and educational components committed to the evaluation and treatment of the entire range of pain, disability, and rehabilitation concerns. This clinical setting is an exceptional site as it serves the target population for this study and there is a group room in the clinic which is an accommodating setting for the intervention to occur.
Participants and Recruitment Methods
The study is registered with Pitt + Me through the University of Pittsburgh, which is a voluntary database of individuals who have agreed to be contacted to participate in potential research studies. The Registry's software matches participants, based on their demographics,
ICD-9/10 codes, in addition to health preferences, with studies for which they may be eligible
(CTSI, 2018) to participate. Study flyers will also be posted at the study clinic. Prospective participants will be screened by research staff members to determine eligibility and reasons for ineligibility will be collected for purposes of adhering to the Consolidated Standards of Reporting Trials (CONSORT) standards [10]. The patients will be informed that if they are eligible to enroll in the study and that they will be compensated up to $165 for full participation.
Sample Size Justification
Power analyses are often used to determine the sample size needed to offer
statistical power to detect a clinically meaningful difference with the specified inferential
statistical test. However, given that this is a small scale RCT, a pilot sample size is instead based
on the pragmatics of recruitment and the necessities for testing feasibility [11].
Inclusion and Exclusion Criteria
Inclusion and exclusion criteria will be assessed by a combination of self-reported measures and review of medical records. Patients will be included if they (1) have chronic pain for > 3 months’ duration, (2) currently prescribed opioid medication, (3) score moderate or high-risk (score of > 4) on the Opioid Risk Tool (ORT). We selected the ORT as opposed to other opioid risk tools due to both the brevity and validity of the instrument [12] (4) English speaking, and ≥ 18 years. Patients will be excluded if they meet any of the following criteria: (1) are receiving active cancer treatment, palliative, and/or end-of-life care as these patients often have unique therapeutic goals, ethical considerations, and typically experience different intensities of pain and varying sensitivities from cancer related symptoms and from the drugs used within their treatment [13] [14]; (2) are pregnant, given that opioids used in pregnancy can be associated with additional risks to both mother and fetus [15]; (3) have experienced a psychotic and/or manic episode in the last 30 days, due to potential issues regarding follow up with this patient population [16]; psychosis and/or mania will be assessed by the psychosis subscale from the Behavior and Symptom Identification Scale which has demonstrated both reliability and validity [17]; (4) plan to leave the Pittsburgh area for an extended period of time within the next 4 months of enrollment.
Treatment as Usual (TAU)
The control group will receive TAU, which entails any other pharmacologic and non-pharmacologic treatments for chronic pain obtained from their healthcare providers. We will systematically document participants’ receipt of TAU in both arms, including medications, pain specialists, physical therapy, psychosocial treatment etc. A TAU control group permits us to estimate retention rates of controls not receiving any active treatment in pain trials, informing the development of an enhanced TAU control in the planned full-scale trial of IPGT.
Integrated Psychosocial Group Treatment (IPGT)
This behavioral intervention blends evidenced based psychosocial treatments for chronic pain and issues pertaining to opioid misuse. The intervention addresses each issue individually and the interconnections between overlapping problems. The IPGT intervention design based on a more recent literature review [18] and then specifically tailored the content to chronic pain patients at risk for opioid misuse. IPGT consists of 6 weekly group sessions of motivational interviewing and behavioral change, self-management, and pain education focused on adherence to treatment and resisting urges to misuse prescription medications. The intervention also entails an education session on overdose education and naloxone distribution.
Format of Group
The IPGT closed group meets once a week for six weeks, with sessions 90 minutes in duration. Table 1. provides a detailed overview of each individual session. The first session is educational, while the remainder of the group will utilize cognitive behavioral therapy, motivational interviewing, mindfulness-based strategies and relaxation techniques while also allowing for emotional and peer support. Topics covered in the remaining five sessions include: pacing and goal setting, negative thinking, coping with stress and anxiety, managing set-backs, treatment adherence, and quality of life. A more comprehensive overview of the session content can be found in Table 1.
Table 1
Psychosocial Components of Integrated Psychosocial Group Treatment
| Integrated Psychosocial Group Treatment (IPGT) Session Content |
| Treatment Strategies | IPGT uses principles encompassing motivational interviewing, behavioral change, self-management and patient empowerment. The treatment model also employs: • Cognitive behavioral therapy, mindfulness-based strategies, stress reduction and relaxation techniques while also allowing for emotional and peer support • Patient education on chronic pain, mental health, and issues surrounding substance misuse, addiction and treatment adherence |
| Session 1 | ¬ The study facilitator welcomes participants, provides an overview of the study, and works on developing group dynamics and therapeutic alliance ¬ The first session is primarily educational and will cover the following topics: •What is pain (acute vs. chronic) •How pain affects the quality of life •Overview of tolerance, physical dependence, and addiction •The continuum of pain, addiction, and pseudoaddiction •Overview of mental health and comorbid chronic pain •The four A’s of pain treatment outcomes ¬ The session is closed with a group debrief and goal-setting for the upcoming week |
| Session 2 | ¬ The session is started with group check-in and goal-setting ¬ The study facilitator introduces the concept of relaxation techniques and leads the group through a visualization exercise ¬ The remainder of the group is spent on medication adherence, education on overdose and naloxone; participants are afforded the opportunity to ask questions ¬ The session is closed with a group debrief and goalsetting for the upcoming week |
| Session 3 | ¬ The session is started with group check-in and goal-setting ¬ The study facilitator introduces the concept of mindfulness and leads the group through a mindfulness exercise ¬ The remainder of the group addresses the topic of “Stages of Change and Pacing Techniques” with a cognitive behavioral approach addressing both issues of chronic pain in addition to issues around medication adherence ¬ The session is closed with a group debrief and goal-setting for the upcoming week |
| Session 4 | ¬ The session is started with group check-in and goal-setting ¬ The study facilitator revisits the concept of relaxation techniques and leads the group through a breathing exercise ¬ The remainder of the group addresses the topic of “Negative Thinking, Fear Avoidance, and Pain Catastrophizing” with a cognitive behavioral approach ¬ The session is closed with a group debrief and goal-setting for the upcoming week |
| Session 5 | ¬ The session is started with group check-in and goal-setting ¬ The study facilitator re-visits the concept of relaxation techniques and leads the group through an imagery exercise ¬ The remainder of the group addresses the topic of “Coping with Stress and Anxiety” with a cognitive behavioral approach ¬ The session is closed with a group debrief and goal-setting for the upcoming week |
| Session 6 | ¬ The session is started with group check-in and goal-setting ¬ The study facilitator revisits the concept mindfulness techniques and leads the group through a mindfulness exercise ¬ The remainder of the group addresses the topic of “Managing Set-Backs, Treatment Adherence, and Quality of Life” with a cognitive behavioral approach ¬ The session is closed with a group debrief and address ways to continue progress post study participation |
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Treatment Fidelity Procedures
To assess treatment fidelity, a master’s level research assistant and master’s level licensed social worker specialized in chronic pain will review all the audiotaped sessions to assess the adherence to the IPGT treatment protocols. Fidelity assessment sheets were created that are based on the contents of each manualized session, which will then be used to indicate whether the components of the session as described in the manual are included in the session. A fidelity score will be computed for each session that represents the percent of essential components of that session that are successfully completed by the interventionist.
Outcome Measures
All outcome measures will be administered by research staff blinded to the intervention assignment. Assessments will be conducted pre- (within 14 days of randomization and beginning treatment), posttreatment (within 2 weeks of completing treatment) and 9 weeks after randomization and post intervention completion.
Feasibility and Acceptability
Primary outcomes will include feasibility and acceptability of IPGT. For the assessment of feasibility, we will track the percentage of patients who receive the 6-session intervention as well as assess the average number of sessions received by the IPGT recipients. We will also capture feasibility by delivery of all intervention component of IPGT recipients. We will examine acceptability of IPGT completion by assessing satisfaction with a 16-question patient satisfaction questionnaire which will assess topics such as: length and frequency of sessions, increased knowledge, cultural competence, value of patient manual, experience of facilitator, effectiveness of peer support. Acceptability will also be assessed by tracking retention of IPGT recipients at the completion of the study and qualitative feedback will also be collected during the patient satisfaction survey and will examine the participants experience with IPGT.
Preliminary Efficacy
There are various preliminary efficacy outcome measures which will assess opioid misuse behaviors, increased knowledge of opioid medications and overdose response, pain severity and interference, and pain catastrophizing.
Opioid Misuse and Knowledge of Opioid Medication and Overdose Response
The Prescription Opioid Misuse Index (POMI) will evaluate if the participant is engaging in aberrant drug taking behavior (doctor shopping, taking medication at higher doses or more frequently than prescribed, and coping with personal issues) [1] and it has demonstrated both validity and reliability [1]. The Drug Abuse Screening Test-10 (DAST-10) will be used for assessing severity of any drug use and has demonstrated clinical validity [19–21]. The Brief Opioid Overdose Knowledge (BOOK) Questionnaire will assess knowledge on overdose and naloxone distribution. The BOOK is a 3-factor scale, representing opioid knowledge (4 items), opioid overdose knowledge (4 items), and opioid overdose response knowledge (4 items). The questionnaire has demonstrated validity [25].
Pain Measures
The Brief Pain Inventory Short Form (BPI) will assess pain severity and interference. The BPI is one of the most commonly used questionnaire to examine severity of pain and the impact of pain on daily functions. The BPI has excellent test-retest reliability, construct validity, and criterion validity [22–24]. The Pain Catastrophizing Scale (PCS) assesses three components of catastrophizing: rumination, magnification, and helplessness. The PCS is a 13-item instrument that has demonstrated both validity and reliability [24, 25].
Behavioral Health and Demographic Characteristics
We will use various standardized mental health and substance use measures to assess differences in patient characteristics at baseline. Depression and anxiety will measure by the Hospital Anxiety and Depression Screen (HADS). The questionnaire is comprised of seven questions which assess anxiety and seven questions which examine depression. HADS has demonstrated both reliability and validity [26]. Post-Traumatic Stress Disorder (PTSD) will be captured with the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5). The PC-PTSD-5 is a five-item measure that reflects the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) PTSD diagnostic criteria and has demonstrated validity [27]. Lastly, we will capture demographic characteristics including: age, gender, marital status, race and ethnicity, education, and employment status.
Analyses
All study analyses will be intent-to-treat. As an initial step, we will compare baseline characteristics of the treatment groups using Fisher's Exact or Wilcoxon-Mann-Whitney tests in order to determine if there are significant baseline differences despite the randomization.
Feasibility an Acceptability Analyses
To examine feasibility, successful delivery of all intervention components to 75% of IPGT recipients will be analyzed by conducting chi-squares; the frequency of withdrawal will be compared between groups (IPGT vs. TAU). Feasibility will further be analyzed by calculating the total number of participants who completed all 6 IPGT sessions divided by total number of IPGT participants. Acceptability will be examined through the application of a Patient Satisfaction Questionnaire, which will include a 16 item 5-point Likert scale. Means and standard deviations will be calculated for each of the questions and delivery of all intervention components to 75% of IPGT recipients will be analyzed by calculating number of recipients retained at 6 weeks divided by number of consented recipients.
Preliminary Efficacy Analyses
We will conduct a descriptive analysis of frequencies, measures of central tendency, and dispersion to examine our acceptability and feasibility outcomes. We also will assess for imbalances in groups including descriptive statistical measures of participant demographic and health characteristics. A priori intent-to-treat analysis of the longitudinal data using linear mixed models will be conducted. Models of longitudinal change will follow the mixed model procedure described by Singer and Willett [28]. We will build 3 separate models for each dependent variable: pain severity, pain interference, and pain catastrophizing. Baseline, post-treatment (6 weeks), and follow up (9 weeks) values will be the three time points used and time will be considered as a numerical value with effect assumed to be linear. The time by treatment interaction will represent the treatment effect. We will adjust variables that are significantly different between IPGT and TAU.