Background
The opioid overdose epidemic continues to surge across the country, resulting in a record number of fatal overdoses in 2017 [
1]. With more than 2 million individuals meeting criteria for opioid use disorder (OUD) [
2], there is need to expand access to evidence-based treatments. Medications for opioid use disorder (MOUD) is the current gold standard treatment for this population [
3]. Of the FDA-approved MOUD, buprenorphine-naloxone (buprenorphine), a long-acting partial opioid agonist, has grown in popularity because of its more flexible administration through office-based programs [
4]. Buprenorphine works by reducing cravings, alleviating withdrawal symptoms, and blocking the euphoric effects of opioids [
5]. Meta-analyses highlight the effectiveness of buprenorphine in reducing adverse outcomes [
6]. However, a significant proportion of patients return to illicit opioid use and/or discontinue treatment before achieving stabilization (i.e., period of time following medication induction in which medication dose is adjusted to be effective in reducing cravings/withdrawal, minimize potential side effects, and eliminate illicit substance use) [
5,
7,
8]. This is notable as early lapses are related to poor treatment prognosis and retention [
8,
50].
A negative reinforcement model of substance use posits that individuals may use opioids to mitigate aversive internal states [
8,
9]. Consistent with this perspective, negative affect has been cited as a primary precipitant of early lapse among opioid users [
10]. Distress tolerance (DT), defined as the perceived or actual ability to handle uncomfortable physical or emotional states, is a transdiagnostic vulnerability factor implicated in the development and maintenance of affective symptoms/disorders and substance use [
11,
12]. DT involves the ability to withstand negative reinforcement opportunities by exerting control over behavioral responding that would otherwise provide immediate relief from distress [
13]. DT is inversely related to a range of drug use outcomes, including frequency and severity of use [
14,
15], premature termination of treatment [
16], and early lapse/relapse [
17,
18]. Preliminary work suggests that addressing DT during substance use treatment may improve outcomes by promoting the ability to persist in goal directed activity even when experiencing distress and discomfort [
19].
Personalized feedback interventions (PFI), such as decisional balance feedback, represent a promising method to effectively motivate engagement in and adherence to buprenorphine treatment, particularly among individuals characterized by low DT. Decisional balance feedback involves an evaluation of the advantages/disadvantages of engaging in a certain behavior (e.g., opioid use), compared to the advantages/disadvantages of an alternative behavior (e.g., abstinence), and also offers strategies for changing problematic behavior (e.g., DT skills training) [
20,
21]. Although PFIs have shown promise for reducing substance use across a variety of adult populations [
21,
22], no integrated protocols exist to enhance motivation and facilitate DT skills training among individuals with OUD.
Given that negative internal states may occur in participants’ natural environments in response to drug cues, stressors, or the context of withdrawal, this population may benefit from a motivational and DT-based intervention that can be delivered on a mobile platform. In the United States almost 95% of adults own a mobile phone [
23]. Text message interventions have demonstrated efficacy for health promotion and behavior change, with personalized messages showing the greatest benefit [
24]. These platforms also offer the advantage of being delivered outside of structured treatment sessions and allow for the content, timing, and frequency of messages to be individually tailored to times when certain skills and motivational reminders are most salient [
25].
This paper describes the study design and procedures for a behavioral treatment development trial that examines the feasibility, acceptability, and preliminary efficacy of a digital health intervention (iCOPE) designed to promote engagement in and adherence to buprenorphine through motivational enhancement and DT skills training among individuals initiating outpatient addiction treatment.
Methods
Study design overview
The current study meets the objectives of Stage I of the NIDA Behavioral Therapies Development Program, which provides a conceptual framework grounded in basic science, for intervention development [
26]. Stage I includes two phases—Stage 1A and Stage 1B. Stage 1A involves the creation of a new intervention, while Stage 1B establishes feasibility through pilot testing [
26]. In Phase 1 (Stage 1A), our team will develop and refine, through formative evaluation, an interactive computer- and text message-delivered PFI that incorporates DT skills training for persons who have elected to initiate outpatient buprenorphine (iCOPE). Specifically, this intervention is designed to promote medication induction and stabilization following standard clinic intake procedures. All participants will receive standard outpatient buprenorphine treatment, including medication visits, counseling, case management, and peer recovery (treatment as usual; TAU). In Phase 2 (Stage 1B), we will conduct a pilot randomized controlled trial. Eighty patients with a history of OUD, actively seeking outpatient buprenorphine, will be randomly assigned to iCOPE or TAU, using a 3:1 randomization ratio. We propose a 3:1 randomization ratio to maximize the information gained about the iCOPE intervention while including a comparison condition. All participants will complete assessments at treatment initiation as well as 1-, 4-, 8- and 12-weeks post-initiation. These data will be used to inform the development of a large-scale, fully-powered trial. At the time of this report, recruitment for Stage 1A is ongoing.
Stage 1A
Qualitative, in-depth, individual interviews are currently being conducted with patients actively engaged in buprenorphine treatment (target N = 24). The sample is balanced by gender, primary type of opioid use (prescription pills; heroin), and phase of recovery [early (≤ 8 weeks of treatment) vs. late (> 8 weeks of treatment)]. Interviews will continue until saturation is achieved. Following informed consent, demographic and clinical data are obtained. Interviews are conducted by the Principal Investigator (KJL) or a trained Research Assistant, and follow a semi-structured interview protocol that stems from primary research questions and project goals. Specific questions focus on participants’ use of computers, mobile phones, and other technologies; prior engagement in MOUD; barriers/facilitators to engaging in MOUD; reactions to and perceived usefulness of proposed intervention; and preferences, benefits, and likelihood of engaging in digital health interventions. All interviews are conducted in a private office to ensure confidentiality and are digitally recorded. Each interview takes approximately 60–90 min to complete; participants receive a $30 gift card for their time/effort. Interviews are transcribed by a professional agency, and the written transcripts are later reviewed to resolve discrepancies.
Qualitative analyses will be conducted to inform intervention development and refinement. Both thematic (deductive) and data driven (inductive) codes will be utilized. Deductive codes will be drawn from the topics in questions used to facilitate the interviews; inductive codes will capture additional concepts that emerge from the participants. Early interviews will be coded by three team members, until stability of the coding structure is reached. All interviews thereafter will be independently coded by two team members using the coding scheme, then compared to ensure agreement. Agreed upon codes will be entered into NVivo. Throughout the process, a framework matrix will be created. This data reduction tool, a matrix of cases and themes based on interview debriefs and individual interview codes, will be used to track emergent ideas and concepts that impact intervention design and future interviews [
27‐
29]. After every few interviews, research team members will examine the framework matrix, identify reoccurring major themes, make changes to intervention content as appropriate, then test the edits in subsequent interviews. This method will allow for quick, iterative turnaround of participant feedback to intervention edits and modifications of interview questions.
We will further refine the intervention by recruiting an additional 16 participants for open pilot testing. These participants will be in the initial 8 weeks of treatment and will be balanced by gender and primary type of opioid use. At the end of the iCOPE intervention, semi-structured interviews, in combination with measures of protocol adherence, will be used to evaluate and then improve upon the intervention’s appropriateness and comprehensibility. During the interviews, participants will be queried about their comfort with technology (computer and text message); ease of using the technology formats; level of understanding of intervention content; perceived usefulness of material; satisfaction with format and content; likelihood of recommending the intervention; likelihood of continued use; and suggestions for improvement. To guide refinements, we will collect data on the feasibility and acceptability of the intervention. Feasibility will be determined by assessing study recruitment and refusal rates, intervention completion, follow-up rates, and rates of study attrition. Acceptability will be determined by the (a) System Usability Scale, a participant-completed, reliable and valid metric for measuring usability and acceptability of technologies; [
30‐
32] and (b) Relative Subjective Count, the quotient of the participant’s estimate of the number of times the system delivers a text, divided by the number of texts actually delivered [
33]. All proposed changes will be integrated into the final version of iCOPE for testing in Phase 2.
Stage 1B
Stage 1B will employ a randomized controlled trial design to pilot test iCOPE relative to the TAU control condition (see description of treatment conditions below). Adult patients (N = 80) meeting eligibility criteria will be randomly assigned to either the iCOPE or TAU conditions.
Following the initial evaluation, in which patients are admitted to buprenorphine treatment, staff will refer potentially eligible patients to study personnel. Interested participants will meet with study personnel in a private setting at the clinic. Informed consent will be obtained, and final eligibility will be determined. Eligible participants will complete a baseline assessment, including two brief behavioral measures of DT (Mirror Tracing and Breath Holding; see Assessments). Participants will then be randomly assigned to iCOPE or TAU. Participants in the iCOPE condition will complete the brief computerized intervention. They will also be informed about the text message element of the intervention and instructed in these procedures. We will recruit 80 participants who will be assigned to condition at a 3:1 ratio, with 60 participants assigned to iCOPE and 20 participants assigned to TAU. Participants will be scheduled to return to the clinic for follow-up appointments consisting of an online survey, behavioral DT measures, and urine collection. Follow-ups will occur at 1-, 4-, 8- and 12-weeks post-treatment initiation.
Participants
Participants will include 80 males and females between the ages of 18 and 75 initiating OUD treatment, specifically the use of buprenorphine. For inclusion, participants must meet current Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), criteria for OUD and have access to a cell phone with text message capability. To reduce the risk of adverse events and potential confounds, we will employ the following exclusion criteria: (1) active suicidality and/or psychosis that would interfere with the ability to participate in the intervention, (2) not fluent in English as translation is beyond the current study resources, and (3) limited mental capacity or inability to provide informed written consent.
Study setting
The Lifespan Recovery Center at Rhode Island Hospital will serve as the proposed recruitment site. The Lifespan Recovery Center is an outpatient addiction treatment program that offers buprenorphine and ancillary services (e.g., counseling, case management, peer recovery). The clinical team includes: four physicians, four therapists, a case manager, and a peer recovery specialist. On average, there are approximately 20 new patient admissions per month. As part of routine clinical care at the Lifespan Recovery Center, patients typically attend an intake evaluation and medication induction appointment, followed by weekly follow-up visits for the initial 8 weeks of treatment (stabilization). Once stabilized, patients continue to attend monthly follow-up appointments for the duration of treatment.
Compensation and retention
In an effort to bolster study retention, we have aligned study follow-up assessments with routine clinic visits. Additionally, follow-up reminders will occur via emails, telephone calls, and text messages. Participants will earn a $25 gift card for completing the initial assessment and a $20 gift card for completing each follow-up assessment. Participants completing all required follow-ups will earn an additional $25 gift card. Participants have the potential to earn up to $130 for completing all study assessments.
Discussion
The prevalence of OUD has reached epidemic rates in United States, and opioid-involved overdoses are now the country’s leading cause of injury deaths [
50]. MOUD, including the use of buprenorphine, is effective at producing significant reductions in illicit opioid use as well as improvements in health-related outcomes (e.g., reduced risk of HIV) [
6,
51]. However, despite the many advantages associated with buprenorphine treatment, nearly half of participants are unable to achieve stabilization [
7], and many patients lapse or discontinue treatment in the initial weeks [
8]. This is notable as early lapses are related to poor treatment prognosis and retention [
8,
52]. Given high rates of noncompliance and/or discontinuation, there have been recent calls to find innovative interventions to enhance motivation, adherence, and retention in buprenorphine treatment [
53].
Consistent with a negative reinforcement model of substance use, aversive internal states, that occur in the context of early periods of abstinence, may contribute to difficulties with buprenorphine stabilization [
54]. Accordingly, an intervention that (a) cultivates motivation for abstinence over and above the reinforcing effects of opioids and (b) teaches adaptive strategies for tolerating physical and psychological discomfort may optimize stabilization on buprenorphine to improve the likelihood of long-term recovery. This Stage 1 behavioral treatment development trial seeks to develop, and pilot test, an innovative digital health intervention that aims to enhance motivation to engage in treatment and increase tolerance of distress to facilitate buprenorphine stabilization by providing skills training and motivational reminders in ‘real-time.’
At the conclusion of this study, our goals are to (1) evaluate the feasibility, acceptability, and preliminary efficacy of the iCOPE intervention components and (2) explore potential mechanisms underlying the effects of the intervention. Results of this study will be used to determine whether to proceed with further testing through a large-scale, fully-powered trial. Even if this study produces null effects of the proposed intervention, the data will still yield valuable information to inform future intervention development efforts.
This work has the potential to improve treatment outcomes by reducing illicit opioid use, increasing adherence/retention, and preventing future incidence of overdose. If successful, this study has high clinical and public health significance by developing and pilot testing the preliminary efficacy of an intervention that may reach a high-risk and vulnerable segment of the population. Further, by leveraging digital health platforms, this proposal has the potential for high scalability and impact.
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