Integrated Services for Pain: Interventions to Reduce Pain Effectively

Chronic Pain Clinical Trial

— INSPIRE  

Official title:

Integrated Health Services to Reduce Opioid Use While Managing Chronic Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03454555
• Other study ID #: PCORI-OPD-1610-37006
• Status: Completed
• Phase: N/A
• Start date: June 21, 2019
• Est. completion date: September 30, 2023

Study information

• Verified date: April 2024
• Source: RTI International
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

What is the research about? Long-term pain -or pain that lasts for months or years-is one of the most common health problems in the United States. Clinicians often treat long-term pain with opioids. Opioids can help ease pain in the short term, but evidence does not support their effectiveness in the long term. For some people, long-term opioid use can lead to addiction and overdose. People need effective options and support to help improve their function and enjoy life as much as possible. What is the research team doing? This study that compared two programs for helping people living with long-term pain to improve their function while managing their pain. People with long-term pain who had been taking opioid medicines for 3 or more months could be in the study. This study was done at primary care and pain care clinics at 3 health systems in North Carolina and Tennessee. The study team assigned people by chance to one of two study programs: (1) Shared Decision Making (SDM) or (2) Cognitive Behavioral Therapy and Motivational Interviewing (CBT+MI). Both programs went by clinical guidelines for opioid prescribing. In the SDM program, the patient and clinician worked together to make decisions that were best for the patient. In the CBT+MI program, the patient learned strategies to better cope with chronic pain. The study team compared the two programs by looking at changes in opioid dose, physical functioning, and pain interference over time. They collected information on prescribed opioid dose from electronic health records. People did surveys at the start of the study and at 6 and 12 months. Study data collection is over, and the study team is analyzing data. Results are forthcoming. The study team worked with an advisory group that included patients, advocates, clinicians, and pain experts. The advisory group met with the study team two to three times per year to provide input on the study.

Description:

Rationale: Up to one-third of Americans suffer from chronic non-cancer pain (CNCP). Opioids are often used to treat CNCP. Once on chronic opioid therapy (COT) individuals often continue with this class of medication for years. Evidence for the effectiveness of COT to treat CNCP is limited, exposing individuals to known risks. Modified or novel pharmacological and nonpharmacological strategies are needed to improve pain management and promote informed decision making regarding possible opioid dose reduction. Study Design and Approach: This is a large-scale, pragmatic randomized controlled trial implementing pharmacotherapy guidelines and behavioral interventions in real-world settings. A pragmatic trial is a study designed to evaluate the effectiveness of interventions in broad patient groups in routine clinical practice. This differs from an explanatory trial, which is designed to evaluate efficacy under ideal conditions. In this trial, the researchers will examine the comparative effectiveness of two approaches to reducing opioid dose for CNCP who are on COT: shared decision making (SDM) and guideline-concordant pharmacotherapy (SDM Arm) versus motivational interviewing plus cognitive behavioral therapy for chronic pain (MI+CBT-CP) and guideline-concordant pharmacotherapy (MI+CBT-CP Arm). This project will evaluate two nonpharmacologic approaches to pain management and opioid reduction in primary care and specialty pain clinics. The approaches are designed to educate medical care providers, educate patients currently being treated for CNCP, help patients address pain and pain coping skills, and enhance patient motivation to reduce or discontinue opioid use. This study will determine the feasibility, effectiveness and potential scalability of these interventions in reducing opioid use in patients who are using ≥ 20 morphine equivalent doses (MED). The study will also assess patient acceptability of the interventions including involvement in their implementation and willingness to incur out-of-pocket costs associated with the visits. Objectives: To conduct a multisite pragmatic trial of two active interventions: SDM as compared with MI+CBT-CP. Primary Objective: * To assess if the interventions result in opioid dose reduction and to compare their effectiveness. Secondary Objectives: - To examine the impact of the interventions on physical function. - To examine the impact of the interventions on pain interference. Timeline: The project commenced in February 2018. Participant recruitment occurred from June 2019 to March 2022. Delivery of the intervention occurred on a rolling basis through March 2023. Recruitment, Screening, Enrollment, and Randomization: The study enrolled 526 participants from primary care and pain clinics at three medical centers in North Carolina and Tennessee. The researchers identified patients who are potentially eligible through electronic health records and contacted these patients with an invitation to participate. A Research Coordinator contacted patients to complete screening, enrollment, and randomization. The researchers randomized enrolled participants to either the SDM Arm or MI+CBT-CP Arm of the intervention. Interventions: In the SDM arm, patients and clinicians engaged in SDM. In the MI+CBT-CP Arm, patients participated in MI+CBT-CP. Patients in both study arms received guideline-concordant pharmacotherapy treatment, based on clinical guidelines for opioid therapy for CNCP. Data Collection: The researchers employed a comprehensive, multi-mode data collection method that included collecting patient-reported outcomes through Web-based and phone-based surveys and leveraging existing harmonized electronic health record (EHR) data. The researchers will use validated measures to measure the impact of the interventions. The researchers will assess the primary outcome, change in opioid dose from baseline, using EHR data at 6 timepoints: 3 months, 6 months, 9 months, 12 months, 15 months, and 18 months. Change from baseline in average daily opioid dose will be measured as prescribed morphine equivalent dose (MED). The researchers will measure the secondary outcomes, physical functioning and pain interference, via participant survey at three timepoints: baseline, 6 months, and 12 months. 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, the 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. The researchers will evaluate clinical outcomes and patient-reported outcomes using cross-sectional and longitudinal intent-to-treat analyses. These analyses will use mixed effects models to compare opioid dose between the two study arms over an 18-month period. The 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 history of substance abuse. Qualitative research methods have been used to obtain participant input on their experiences.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 526
• Est. completion date: September 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Aged 18 to 85 years
• History of chronic non-cancer pain (CNCP)
• Receiving high-dose chronic opioid therapy for CNCP as evidenced by current or most recent prescription of an average daily morphine-equivalent dose of 20 mg or greater
• Receiving care at a participating clinic from a participating provider, as evidenced by at least 1 in-person visit within the past 12 months.

Exclusion Criteria:

• Not meeting the above inclusion criteria
• Opioid use is for pain directly related to an active cancer diagnosis
• Opioid use is for maintenance treatment of an opioid use disorder
• Suicide attempt within the past 3 years
• Active suicidal ideation
• Currently receiving Cognitive-Behavioral Therapy (CBT)
• Non-English speaking
• Other reason at the discretion of the investigator

Related Conditions & MeSH terms

• Chronic Pain

Intervention

Behavioral:
• Shared Decision Making
The Shared Decision Making (SDM) intervention is a patient-provider communication intervention to explore and compare treatment options, assess a patient's values and preferences, and reach a shared decision about chronic pain treatment. The intervention will have both clinician and patient educational components. The content of the clinician component will be based on the Agency for Healthcare Research and Quality's "SHARE: Seek, Help, Assess, Reach, Evaluate" Approach, which is a 5-step process for shared decision making that includes exploring and comparing the benefits, harms, and risks of each option through meaningful dialogue about what matters most to the patient. Participants randomized to Arm 1 will have their study visits and opioid use managed by an SDM-trained clinician at their practice.
• Motivational Interviewing and Cognitive Behavioral Therapy for Chronic Pain
The Motivational Interviewing and Cognitive Behavioral Therapy for Chronic Pain (MI+CBT-CP) intervention is an empirically based behavioral pain management behavioral therapy intervention, including MI to enhance motivation for active participation in the CBT-CP, and the use of CBT-CP to enhance pain coping skills. One individual MI session will focus on patient engagement and enhancing a patient's own intrinsic motivation for CBT-CP participation. MI will also be woven into the group CBT-CP sessions. We will deliver 8 sessions of CBT-CP, as is standard in a group setting, in-person or virtually.

Locations

Country	Name	City	State
United States	University of North Carolina Health Care System	Chapel Hill	North Carolina
United States	Duke University Health System	Durham	North Carolina
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (5)

Lead Sponsor	Collaborator
RTI International	Duke Health, Patient-Centered Outcomes Research Institute, University of North Carolina Health Care System, Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (7)

Agency for Healthcare Research and Quality. (2017, February). The SHARE Approach. Retrieved from http://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/index.html

Chou R, Deyo R, Devine B, Hansen R, Sullivan S, Jarvik JG, Blazina I, Dana T, Bougatsos C, Turner J. The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain. Evid Rep Technol Assess (Full Rep). 2014 Sep;(218):1-219. doi: 10.23970/AHRQEPCERTA218. — View Citation

Edlund MJ, Thomas SM, Wagner LK, Thompson JE, Wu LT, Dolor RJ, Chelminski PR, Ives TJ, Archer KR, Dewey CM, Sullivan MD, McCormack LA; INSPIRE Study Team. Design of a Multicenter Randomized Controlled Trial comparing the effectiveness of shared decision making versus motivational interviewing plus cognitive behavioral therapy for voluntary opioid tapering: The INSPIRE study protocol. Contemp Clin Trials. 2024 Feb;137:107410. doi: 10.1016/j.cct.2023.107410. Epub 2023 Dec 12. — View Citation

Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC): National Academies Press (US); 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK91497/ — View Citation

Martin BC, Fan MY, Edlund MJ, Devries A, Braden JB, Sullivan MD. Long-term chronic opioid therapy discontinuation rates from the TROUP study. J Gen Intern Med. 2011 Dec;26(12):1450-7. doi: 10.1007/s11606-011-1771-0. Epub 2011 Jul 13. — View Citation

Monticone M, Ambrosini E, Cedraschi C, Rocca B, Fiorentini R, Restelli M, Gianola S, Ferrante S, Zanoli G, Moja L. Cognitive-behavioral Treatment for Subacute and Chronic Neck Pain: A Cochrane Review. Spine (Phila Pa 1976). 2015 Oct 1;40(19):1495-504. doi: 10.1097/BRS.0000000000001052. — View Citation

Vanderlip ER, Sullivan MD, Edlund MJ, Martin BC, Fortney J, Austen M, Williams JS, Hudson T. National study of discontinuation of long-term opioid therapy among veterans. Pain. 2014 Dec;155(12):2673-2679. doi: 10.1016/j.pain.2014.09.034. Epub 2014 Sep 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from Baseline in Pain Intensity on the 3-item Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity at Month 6	The PROMIS-Pain Intensity is a validated, self-reported instrument assessing pain intensity over the past 7 days. Possible scores on each item range in value from 1 (no pain) to 5 (very severe). Higher scores indicate higher pain intensity and worse health. Change = Month 6 Score - Baseline Score.	Baseline and Month 6
Other	Change from Baseline in Pain Intensity on the 3-item Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity at Month 12	The PROMIS-Pain Intensity is a validated, self-reported instrument assessing pain intensity over the past 7 days. Possible scores on each item range in value from 1 (no pain) to 5 (very severe). Higher scores indicate higher pain intensity and worse health. Change = Month 12 Score - Baseline Score.	Baseline and Month 12
Other	Change from Baseline in Anxiety on the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress - Anxiety at Month 6	The PROMIS-Emotional Distress-Anxiety is a validated, self-reported instrument assessing anxiety over the past 7 days. Anxiety measures self-reported fear, anxiety, hyperarousal, and somatic symptoms related to arousal. Anxiety is best differentiated by symptoms that reflect autonomic arousal and experience of threat. Possible scores on each item range in value from 1 (never) to 5 (always). Higher scores indicate higher anxiety and worse health. Change = Month 6 Score - Baseline Score.	Baseline and Month 6
Other	Change from Baseline in Anxiety on the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress - Anxiety at Month 12	The PROMIS-Emotional Distress-Anxiety is a validated, self-reported instrument assessing anxiety over the past 7 days. Anxiety measures self-reported fear, anxiety, hyperarousal, and somatic symptoms related to arousal. Anxiety is best differentiated by symptoms that reflect autonomic arousal and experience of threat. Possible scores on each item range in value from 1 (never) to 5 (always). Higher scores indicate higher anxiety and worse health. Change = Month 12 Score - Baseline Score.	Baseline and Month 12
Other	Change from Baseline in Depression on the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Depression at Month 6	The PROMIS-Emotional Distress-Depression is a validated, self-reported instrument assessing depression over the past 7 days. Depression measures self-reported negative mood, views of self, social cognition, and decreased positive affect and engagement. Possible scores on each item range in value from 1 (never) to 5 (always). Higher scores indicate higher depression and worse health. Change = Month 6 Score - Baseline Score.	Baseline and Month 6
Other	Change from Baseline in Depression on the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) Emotional Distress-Depression at Month 12	The PROMIS-Emotional Distress-Depression is a validated, self-reported instrument assessing depression over the past 7 days. Depression measures self-reported negative mood, views of self, social cognition, and decreased positive affect and engagement. Possible scores on each item range in value from 1 (never) to 5 (always). Higher scores indicate higher depression and worse health. Change = Month 12 Score - Baseline Score.	Baseline and Month 12
Other	Change from Baseline in Pain Severity on the 4-item Brief Pain Inventory (BPI) Pain Severity at Month 6	The BPI Pain Severity is a validated, self-reported instrument assessing pain severity at its worst and least in the past 7 days, on average, and right now. Possible scores on each item range from 0 (no pain) to 10 (pain as bad as you can imagine). Higher scores indicate higher pain severity and worse health. Change = Month 6 Score - Baseline Score.	Baseline and Month 6
Other	Change from Baseline in Pain Severity on the 4-item Brief Pain Inventory (BPI) Pain Severity at Month 12	The BPI Pain Severity is a validated, self-reported instrument assessing pain severity at its worst and least in the past 7 days, on average, and right now. Possible scores on each item range from 0 (no pain) to 10 (pain as bad as you can imagine). Higher scores indicate higher pain severity and worse health. Change = Month 12 Score - Baseline Score.	Baseline and Month 12
Other	Change from Baseline in Pain Interference on the 7-item Brief Pain Inventory (BPI) Pain Interference at Month 6	The BPI Pain Interference is a validated, self-reported instrument assessing pain interference over the past 7 days in 7 categories: general activity, walking, work, mood, enjoyment of life, relation with others, and sleep. Possible scores on each item range from 0 (does not interfere) to 10 (completely interferes). Higher scores indicate higher pain interference and worse health. Change = Month 6 Score - Baseline Score.	Baseline and Month 6
Other	Change from Baseline in Pain Interference on the 7-item Brief Pain Inventory (BPI) Pain Interference at Month 12	The BPI Pain Interference is a validated, self-reported instrument assessing pain interference over the past 7 days in 7 categories: general activity, walking, work, mood, enjoyment of life, relation with others, and sleep. Possible scores on each item range from 0 (does not interfere) to 10 (completely interferes). Higher scores indicate higher pain interference and worse health. Change = Month 12 Score - Baseline Score.	Baseline and Month 12
Other	Discontinuation of Opioid Medications at Month 12	Discontinuation of opioid medications at Month 12 is assessed with a self-reported item newly developed for this study and electronic health record (EHR) data. Discontinuation will be defined as a response of "No" to a question on the Month 12 participant survey that asks: "Are you currently taking an opioid medicine now? Commonly prescribed opioids include hydrocodone, oxycodone, codeine, morphine, and fentanyl" AND no opioid prescriptions in the EHR within 15 days prior to Month 12 through Month 18.	Month 12
Other	Intent to Taper at Baseline	Intent to Taper is assessed with a self-reported item, newly developed for this study, that assesses intent to reduce the amount of opioids taken: "Please say how much you agree with this statement: 'Reducing the amount of opioid medicines I take is a goal of mine.'" Possible response options include Strongly Agree, Agree, Uncertain, Disagree, and Strongly Disagree. In addition to reporting the frequency of initial response options, responses of Strongly Agree and Agree will be re-classified as an intent to taper, while Uncertain, Disagree, and Strongly Disagree will be re-classified as no intent to taper.	Baseline
Other	Intent to Taper at Month 6	Intent to Taper is assessed with a self-reported item, newly developed for this study, that assesses intent to reduce the amount of opioids taken: "Please say how much you agree with this statement: 'Reducing the amount of opioid medicines I take is a goal of mine.'" Possible response options include Strongly Agree, Agree, Uncertain, Disagree, and Strongly Disagree. In addition to reporting the frequency of initial response options, responses of Strongly Agree and Agree will be re-classified as an intent to taper, while Uncertain, Disagree, and Strongly Disagree will be re-classified as no intent to taper.	Month 6
Other	Intent to Taper at Month 12	Intent to Taper is assessed with a self-reported item, newly developed for this study, that assesses intent to reduce the amount of opioids taken: "Please say how much you agree with this statement: 'Reducing the amount of opioid medicines I take is a goal of mine.'" Possible response options include Strongly Agree, Agree, Uncertain, Disagree, and Strongly Disagree. In addition to reporting the frequency of initial response options, responses of Strongly Agree and Agree will be re-classified as an intent to taper, while Uncertain, Disagree, and Strongly Disagree will be re-classified as no intent to taper.	Month 12
Other	Relative opioid use self-report at Month 6	Opioid use relative to baseline is assessed with a self-reported item, newly developed for this study: "Since you started taking part in this study, would you say that your overall use of opioids has increased, stayed about the same, or decreased? In thinking about your "overall use" we ask you consider how often you take the opioid medicine, the different types of opioid medicines, and their amounts." Possible response options include: My overall use of opioids has increased; My overall use of opioids has stayed about the same; and My overall use of opioids has decreased.	Month 6
Other	Relative opioid use self-report at Month 12	Opioid use relative to baseline is assessed with a self-reported item, newly developed for this study: "Since you started taking part in this study, would you say that your overall use of opioids has increased, stayed about the same, or decreased? In thinking about your "overall use" we ask you consider how often you take the opioid medicine, the different types of opioid medicines, and their amounts." Possible response options include: My overall use of opioids has increased; My overall use of opioids has stayed about the same; and My overall use of opioids has decreased.	Month 12
Other	Protocol-Specified Adverse Events (AEs) through Month 12	Three different types of AEs will be collected throughout the intervention phase of the study (from randomization to 12-months post-randomization): 1) opioid withdrawal or overdose, 2) suicidality risk, and 3) death. AEs will be identified and reported from case report forms, the 6 and 12-month follow-up surveys, and deaths from the electronic medical records (based on International Classification of Diseases (ICD)-10 codes). To identify duplicate AE reporting and corroborate AE details, we collect AE type and onset date in each database. If the same AE is reported in multiple different databases, it will only be counted as one AE. The total number of AEs as well as any documented AE will be examined.	Baseline Through Month 12
Primary	Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 3	The primary outcome will be derived from electronic health records. Total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period and dividing by the number of days supplied. Opioid dose will be calculated as the prescribed milligrams of daily MED averaged over the 90 days prior to randomization and averaged over 90 days for the time period of 3 months post-randomization. Change in daily opioid dose will be computed as the difference between the dose calculated during that period and the dose from the baseline period.	Baseline and Month 3
Primary	Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 6	The primary outcome will be derived from electronic health records. Total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period and dividing by the number of days supplied. Opioid dose will be calculated as the prescribed milligrams of daily MED averaged over the 90 days prior to randomization and averaged over 90 days for the time period of 6 months post-randomization. Change in daily opioid dose will be computed as the difference between the dose calculated during that period and the dose from the baseline period.	Baseline and Month 6
Primary	Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 9	The primary outcome will be derived from electronic health records. Total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period and dividing by the number of days supplied. Opioid dose will be calculated as the prescribed milligrams of daily MED averaged over the 90 days prior to randomization and averaged over 90 days for the time period of 9 months post-randomization. Change in daily opioid dose will be computed as the difference between the dose calculated during that period and the dose from the baseline period.	Baseline and Month 9
Primary	Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 12	The primary outcome will be derived from electronic health records. Total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period and dividing by the number of days supplied. Opioid dose will be calculated as the prescribed milligrams of daily MED averaged over the 90 days prior to randomization and averaged over 90 days for the time period of 12 months post-randomization. Change in daily opioid dose will be computed as the difference between the dose calculated during that period and the dose from the baseline period.	Baseline and Month 12
Primary	Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 15	The primary outcome will be derived from electronic health records. Total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period and dividing by the number of days supplied. Opioid dose will be calculated as the prescribed milligrams of daily MED averaged over the 90 days prior to randomization and averaged over 90 days for the time period of 15 months post-randomization. Change in daily opioid dose will be computed as the difference between the dose calculated during that period and the dose from the baseline period.	Baseline and Month 15
Primary	Change From Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 18	The primary outcome will be derived from electronic health records. Total morphine equivalents for each prescription will be calculated by multiplying the quantity of each prescription by the strength of the prescription (milligrams of opioid per unit dispensed). The quantity-strength product is then multiplied by conversion factors to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The total average dose in morphine equivalents per day supplied is calculated by summing the morphine equivalents for each prescription filled during a given period and dividing by the number of days supplied. Opioid dose will be calculated as the prescribed milligrams of daily MED averaged over the 90 days prior to randomization and averaged over 90 days for the time period of 18 months post-randomization. Change in daily opioid dose will be computed as the difference between the dose calculated during that period and the dose from the baseline period.	Baseline and Month 18
Primary	Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 3	Percent change is difference from baseline value divided by the baseline value and multiplied by 100. Positive values indicate an increase in opioid use from baseline, while negative values indicates a decrease from baseline.	Baseline and Month 3
Primary	Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 6	Percent change is difference from baseline value divided by the baseline value and multiplied by 100. Positive values indicate an increase in opioid use from baseline, while negative values indicates a decrease from baseline.	Baseline and Month 6
Primary	Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 9	Percent change is difference from baseline value divided by the baseline value and multiplied by 100. Positive values indicate an increase in opioid use from baseline, while negative values indicates a decrease from baseline.	Baseline and Month 9
Primary	Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 12	Percent change is difference from baseline value divided by the baseline value and multiplied by 100. Positive values indicate an increase in opioid use from baseline, while negative values indicates a decrease from baseline.	Baseline and Month 12
Primary	Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 15	Percent change is difference from baseline value divided by the baseline value and multiplied by 100. Positive values indicate an increase in opioid use from baseline, while negative values indicates a decrease from baseline.	Baseline and Month 15
Primary	Percent Change from Baseline in Average Daily Opioid Dose in Morphine Equivalent Dose (MED) at Month 18	Percent change is difference from baseline value divided by the baseline value and multiplied by 100. Positive values indicate an increase in opioid use from baseline, while negative values indicates a decrease from baseline.	Baseline and Month 18
Primary	Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 3	Dichotomous variable indicating a decrease of 10 MED or more from baseline.	Baseline and Month 3
Primary	Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 6	Dichotomous variable indicating a decrease of 10 MED or more from baseline.	Baseline and Month 6
Primary	Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 9	Dichotomous variable indicating a decrease of 10 MED or more from baseline.	Baseline and Month 9
Primary	Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 12	Dichotomous variable indicating a decrease of 10 MED or more from baseline.	Baseline and Month 12
Primary	Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 15	Dichotomous variable indicating a decrease of 10 MED or more from baseline.	Baseline and Month 15
Primary	Change from Baseline of at least 10 Morphine Equivalent Dose (MED) at Month 18	Dichotomous variable indicating a decrease of 10 MED or more from baseline.	Baseline and Month 18
Secondary	Change from Baseline in Pain Interference on the 8-item Patient-Reported Outcomes Measurement Information System - Pain Interference (PROMIS-PI) at Month 6	The PROMIS-PI is a validated, self-reported instrument assessing pain interference over the past 7 days. Pain interference is a measure of the extent to which pain interferes with patient physical, mental, and social activities. Possible scores on each item range in value from 1 (not at all) to 5 (very much). Higher scores indicate higher pain interference and worse health. Change = Month 6 Score - Baseline Score.	Baseline and Month 6
Secondary	Change from Baseline in Pain Interference on the 8-item Patient-Reported Outcomes Measurement Information System - Pain Interference (PROMIS-PI) at Month 12	The PROMIS-PI is a validated, self-reported instrument assessing pain interference over the past 7 days. Pain interference is a measure of the extent to which pain interferes with patient physical, mental, and social activities. Possible scores on each item range in value from 1 (not at all) to 5 (very much). Higher scores indicate higher pain interference and worse health. Change = Month 12 Score - Baseline Score.	Baseline and Month 12
Secondary	Change from Baseline in Physical Functioning on the 8-item Patient-Reported Outcomes Measurement Information System - Physical Functioning (PROMIS-PF) at Month 6	The PROMIS-PF is a validated, self-reported instrument assessing physical functioning over the past 7 days. Physical functioning measures one's upper extremities (dexterity), lower extremities (walking and mobility), central regions (back and neck), and instrumental activities of daily living.; Possible scores on each item range in value from 1 (without any difficulty) to 5 (unable to do). Higher scores indicate higher physical functioning and better health. Change = Month 6 Score - Baseline Score.	Baseline and Month 6
Secondary	Change from Baseline in Physical Functioning on the 8-item Patient-Reported Outcomes Measurement Information System - Physical Functioning (PROMIS-PF) at Month 12	The PROMIS-PF is a validated, self-reported instrument assessing physical functioning over the past 7 days. Physical functioning measures one's upper extremities (dexterity), lower extremities (walking and mobility), central regions (back and neck), and instrumental activities of daily living.; Possible scores on each item range in value from 1 (without any difficulty) to 5 (unable to do). Higher scores indicate higher physical functioning and better health. Change = Month 12 Score - Baseline Score.	Baseline and Month 12

External Links

•   Comparing Two Ways to Help Patients Manage Long-Term Pain (RTI International)