Integrated Health Services to Reduce Opioid Use While Managing Chronic Pain

Study Design and Approach This is a large-scale randomized pragmatic trial of implementing
pharmacotherapy guidelines and behavioral interventions in real-world settings. This study
provides the opportunity to advance the science on effectiveness-implementation hybrid study
designs because we can assess both clinical effectiveness and implementation issues.

In this trial, the researchers will examine the comparative effectiveness of two approaches
to reducing opioid dosages for chronic non-cancer patients (CNCP) who are on chronic opioid
therapy (COT): shared decision making (SDM) and guideline-concordant pharmacotherapy (Arm 1)
compared with cognitive behavioral therapy for chronic pain and motivational interviewing
(CBT-CP+MI) and guideline-concordant pharmacotherapy (Arm 2).

Rationale:

Believing that an intervention will have a positive outcome is a key tenet of Social Learning
Theory and self-efficacy is a main tenet of Bandura's Social Cognitive theory that refers to
one's belief in their ability to succeed in specific situations. Self-efficacy has
consistently been demonstrated as a reliable predictor of numerous health-related outcomes
and is one of the primary constructs targeted by CBT for individuals with chronic pain. We
posit that enhancing patients' self-efficacy, knowledge, and skills for managing their pain
will lead to decreases in pain interference, self-reported pain status, and symptoms of
anxiety and depression. Ultimately, this will lead to increases in physical functioning, and
for some, decreases in opioid use or discontinuation of opioid use. Our model further
acknowledges that there are certain benefit-risk tradeoffs involved with this study. For
example, the intended effect of decreased opioid use in the CBT-CP+MI arm may also result in
increased reports of pain. Our analyses will explore these and other unintended effects to
the extent possible. Further, the use of CBT-CP+MI is expected to influence outcomes through
various other intermediate factors (e.g., reduced negative thought that "nothing can be done
to help my pain").

Aims:

The research team will examine the impact of the 2 approaches on several outcomes. The study
will examine which set of patients have greater opioid dose reduction, greater rates of
opioid discontinuation, improved functioning, and/or lower pain scores.

The specific aims are:

Aim 1: To test whether CNCP patients who receive guideline-concordant pharmacotherapy
integrated with a CBT-CP+MI intervention (Arm 2) have greater opioid dose reduction relative
to their counterparts, who receive guideline-concordant pharmacotherapy integrated with SDM
(Arm 1).

Aim 2: To test whether CNCP patients who receive guideline-concordant pharmacotherapy
integrated with an CBT-CP+MI intervention (Arm 2) have greater rates of opioid
discontinuation relative to their counterparts, who receive guideline-concordant
pharmacotherapy integrated with SDM (Arm 1).

Aim 3: To test whether CNCP patients who receive guideline-concordant pharmacotherapy
integrated with an CBT-CP+MI intervention (Arm 2) have improved functioning relative to their
counterparts, who receive guideline-concordant pharmacotherapy integrated with SDM (Arm 1).

Aim 4: To test whether CNCP patients who receive guideline-concordant pharmacotherapy
integrated with an CBT-CP+MI intervention (Arm 2) have lower pain scores relative to their
counterparts, who receive guideline-concordant pharmacotherapy integrated with SDM (Arm 1).

The research team chose these comparison arms and outcomes based on input from patients,
patient advocates, and therapists.

Timeline:

The project commenced in February 2018. In 2018, researchers will develop a formal study
protocol documenting the approach and implementation steps, and then proceed with requesting
Institutional Review Board (IRB) approval. Researchers will finalize arrangements with
clinical practices in 2018. The study team will conduct clinician training related to the
interventions to promote consistency in its delivery across the various clinical practices
prior to initiating the intervention.

Recruitment, Screening, Enrollment, and Randomization:

The proposed study will enroll 530 participants in each arm, from primary care and pain
clinics at three medical centers. Participants will have used opioids at the level of 50 mg
or greater daily morphine equivalent doses (MED) for 90 or more days, will not have a
terminal cancer diagnosis, and will not currently be in psychotherapy.

Patient recruitment will occur on a rolling basis beginning early in 2019 and last for up to
26 months. Delivery of the intervention will also occur on a rolling basis with the
recruitment process. We will identify eligible patients monthly and will invite them to
participate in the study. Patients who are potentially eligible will be identified through
electronic health records (EHRs) and contacted by mail and phone with an invitation to
participate. Interested patients will be met at their next clinic visit by a Research
Coordinator to complete additional screening, enrollment, and randomization.

The study will use real-time randomization to limit participant loss prior to treatment.
Eligible patients will be randomized using a stratified, permuted-block design, as this
constrained randomization approach ensures balance between treatment groups within each of
the 3 clinical institutions (our only stratification factor) at the completion of each block.
Consequently, throughout the trial, the treatment arms will have approximately equal sample
sizes both within a site and across the study. Patients will be provided study information
based on their treatment assignment. Patients assigned to Arm 2 will be scheduled for initial
MI and CBT-CP sessions.

Interventions:

In Arm 1, patients and clinicians will engage in Shared Decision Making (SDM). In Arm 2,
patients will participate in cognitive behavioral therapy for chronic pain (CBT-CP) and
motivational interviewing (MI).

Patients in both study arms will receive guideline-concordant pharmacotherapy treatment,
based on clinical guidelines for opioid therapy for CNCP. Guideline-concordant care specifies
current best practices for COT, and the treatment will include the following: patient risk
assessment, including screening for prior substance use disorders; screening for behavioral
health issues; regular monitoring for pain/analgesia with self-reported pain scores (0 to 10,
with 10 = worst possible pain) at each visit; urine drug screens; elicitation of adverse
reactions or aberrant medication behavior; and patient education and goal setting.

Because this is a pragmatic trial, we will not go to excessive lengths to ensure patient
adherence, as might be done in an efficacy trial. If a patient misses a session, we will call
him or her once, as would be done in most clinics.

Control variables will include demographic characteristics, intervention dosage for a subset
of the analyses (e.g., number of intervention sessions attended, overall comorbidity using
the Charlson Comorbidity Index, mental health disorders, and number and type of CNCP
conditions per ICD-9 (International Statistical Classification of Diseases and Related Health
Problems 9th edition) codes. Comorbidities will be extracted from EHR data.

Data Analysis and Reporting:

In a large pragmatic trial such as the one planned, the probability is small that the groups
will have imbalance by age, sex, health behaviors, or other measured or unmeasured possible
confounding factors. Nevertheless, researchers will assess whether randomization has
successfully created comparable groups by descriptively comparing their baseline demographic
characteristics and potential confounders, including baseline pain score, comorbidities,
opioid dosage, and number and type of CNCP conditions.

Researchers will evaluate clinical outcomes and patient-reported outcomes using longitudinal
analyses. Analyses will use longitudinal (mixed effects) models to compare opioid dose over
18 months between the two study arms. Time-to-event models will be used to compare time until
discontinuation of opiates between study arms. Researchers also will explore differences in
the intervention effect according to participant characteristics, such as age, sex, baseline
pain level, baseline opioid dose, and the presence of physical comorbidities, mental health
comorbidities, or a history of substance abuse.

Inclusion Criteria:

- Participants will be patients at participating primary care or specialty pain
management clinics at study sites

- Patients will be 18-75 years,

- Patients will have used opioids at the level of ≥50 mg daily MED for 90 or more days
(based on EHR data).

- Patients will not have a terminal cancer diagnosis

- Patients will not currently be in psychotherapy (based on self-report).

Exclusion Criteria:

- Patients whose providers refuse permission will not be eligible.