Trial Outcomes & Findings for Cognitive Behavioral Therapy and Chronic Pain Self-Management Within the Context of Opioid Reduction: The EMPOWER Study (NCT NCT03445988)

Last Updated: 2025-03-24

Results Overview

Opioid tapering success was defined as either: 50% reduction in opioid dose (change in MEDD baseline to 12 months) and no significantly increased pain (≤ 1 point increase in PROMIS pain intensity score from baseline to 12 months), or; no opioid dose increase (baseline MEDD to 12 months) and significant pain relief (≥ 2 points decrease in PROMIS pain intensity score). Pain intensity score: Patient self-reported pain intensity on 11 point (0-10) numerical rating scale where a lower score means more pain relief. MEDD: Morphine Equivalent Daily Dose. PROMIS: Patient-Reported Outcomes Measurement Information System.

Recruitment status

COMPLETED

Study phase

Target enrollment

1462 participants

Primary outcome timeframe

Baseline and 12 months

Results posted on

2025-03-24

Participant Flow

We partnered with seven study sites that included four outpatient primary care and Veterans health care and three pain clinics in five states (Arizona, California, Colorado, Pennsylvania, and Utah). At all sites, patient recruitment (August 2018-November 2022) was enhanced by using several methods: identifying eligibility in medical records, in-house advertising, external community-based advertising, and use of the CHOIR database at Stanford University.

EMPOWER (opioid taper study; 3-arm randomized): 53 patients who provided consent did not complete their baseline survey; 562 participants completed their baseline survey and were randomized. VALUE (national observational study; non-randomized): 37 individuals who provided consent did not complete their baseline survey; 810 participants completed their baseline survey.

Participant milestones

Participant milestones
Measure	Cognitive Behavioral Therapy for Chronic Pain (Pain-CBT) A trained psychologist delivers pain-CBT to individual patients or groups of patients with chronic pain. Group treatment is delivered across 8 weekly sessions that last for 2 hours each. Pain-CBT incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session. Pain-CBT is effective for reducing pain intensity, pain catastrophizing, depression and social impacts.	Chronic Pain Self Management Program (CPSMP) The CPSMP is similar to pain-CBT in format and content but is peer-led, and is effective across pain conditions (e.g., back pain, arthritis) for improving pain and pain self-efficacy. The CPSMP consists of six weekly 2-hour group sessions in which two peer co-leaders provide patient education about pain, effective self-management, pain impacts, and other symptoms from a highly structured manual. Peers are people with chronic pain who live in the communities in which they teach. For this project, at least one peer facilitator per workshop will have had experience with prescription opioid use. Intervention fidelity is determined by having a trained observer with a checklist attend random workshop sessions. Similar to pain-CBT, CPSMP incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session.	Taper Only (Usual Care) Participants allocated to 'Taper Only' will engage in a physician-guided, patient-centered opioid tapering program without additional behavioral intervention.	Observational Arm (The VALUE Study) Participants that do not wish to reduce their opioid medications but are otherwise eligible and interested in the research study will be offered participation in the observational arm. The observational arm of the study will not include interventions of any kind and will only collect survey data for the year following consent.
Overall Study STARTED	203	168	191	810
Overall Study COMPLETED	177	137	159	735
Overall Study NOT COMPLETED	26	31	32	75

Reasons for withdrawal

Reasons for withdrawal
Measure	Cognitive Behavioral Therapy for Chronic Pain (Pain-CBT) A trained psychologist delivers pain-CBT to individual patients or groups of patients with chronic pain. Group treatment is delivered across 8 weekly sessions that last for 2 hours each. Pain-CBT incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session. Pain-CBT is effective for reducing pain intensity, pain catastrophizing, depression and social impacts.	Chronic Pain Self Management Program (CPSMP) The CPSMP is similar to pain-CBT in format and content but is peer-led, and is effective across pain conditions (e.g., back pain, arthritis) for improving pain and pain self-efficacy. The CPSMP consists of six weekly 2-hour group sessions in which two peer co-leaders provide patient education about pain, effective self-management, pain impacts, and other symptoms from a highly structured manual. Peers are people with chronic pain who live in the communities in which they teach. For this project, at least one peer facilitator per workshop will have had experience with prescription opioid use. Intervention fidelity is determined by having a trained observer with a checklist attend random workshop sessions. Similar to pain-CBT, CPSMP incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session.	Taper Only (Usual Care) Participants allocated to 'Taper Only' will engage in a physician-guided, patient-centered opioid tapering program without additional behavioral intervention.	Observational Arm (The VALUE Study) Participants that do not wish to reduce their opioid medications but are otherwise eligible and interested in the research study will be offered participation in the observational arm. The observational arm of the study will not include interventions of any kind and will only collect survey data for the year following consent.
Overall Study Lost to Follow-up	14	26	27	66
Overall Study Withdrawal by Subject	7	4	3	5
Overall Study Death (unrelated to study)	5	1	2	4

Baseline Characteristics

Data from the two studies (EMPOWER and VALUE) were analyzed separately.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cognitive Behavioral Therapy for Chronic Pain (Pain-CBT) n=203 Participants A trained psychologist delivers pain-CBT to individual patients or groups of patients with chronic pain. Group treatment is delivered across 8 weekly sessions that last for 2 hours each. Pain-CBT incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session. Pain-CBT is effective for reducing pain intensity, pain catastrophizing, depression and social impacts.	Chronic Pain Self Management Program (CPSMP) n=168 Participants The CPSMP is similar to pain-CBT in format and content but is peer-led, and is effective across pain conditions (e.g., back pain, arthritis) for improving pain and pain self-efficacy. The CPSMP consists of six weekly 2-hour group sessions in which two peer co-leaders provide patient education about pain, effective self-management, pain impacts, and other symptoms from a highly structured manual. Peers are people with chronic pain who live in the communities in which they teach. For this project, at least one peer facilitator per workshop will have had experience with prescription opioid use. Intervention fidelity is determined by having a trained observer with a checklist attend random workshop sessions. Similar to pain-CBT, CPSMP incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session.	Taper Only (Usual Care) n=191 Participants Participants allocated to 'Taper Only' will engage in a physician-guided, patient-centered opioid tapering program without additional behavioral intervention.	Observational Arm (the VALUE Study) n=810 Participants Participants that do not wish to reduce their opioid medication(s) but are otherwise eligible and interested in the research study will be offered participation in the observational arm. The observational arm of the study will not include interventions of any kind and will only collect survey data for the year following consent. Data from the VALUE study will be analyzed separately from EMPOWER (randomized).	Total n=1372 Participants Total of all reporting groups
Age, Continuous EMPOWER Study (randomized)	58 years STANDARD_DEVIATION 13 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	59 years STANDARD_DEVIATION 12 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	56 years STANDARD_DEVIATION 13 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	58 years STANDARD_DEVIATION 13 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Age, Continuous VALUE Study (non-randomized)	—	—	—	54.5 years STANDARD_DEVIATION 10.8 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	54.5 years STANDARD_DEVIATION 10.8 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Sex/Gender, Customized EMPOWER Study (randomized) · Female	113 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	79 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	104 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	296 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Sex/Gender, Customized EMPOWER Study (randomized) · Male	90 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	89 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	87 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	266 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Sex/Gender, Customized EMPOWER Study (randomized) · Unknow or not reported	0 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	0 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Sex/Gender, Customized VALUE Study (non-randomized) · Female	—	—	—	652 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	652 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Sex/Gender, Customized VALUE Study (non-randomized) · Male	—	—	—	154 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	154 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Sex/Gender, Customized VALUE Study (non-randomized) · Unknow or not reported	—	—	—	4 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	4 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Ethnicity (NIH/OMB) EMPOWER Study (randomized) · Hispanic or Latino	24 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	12 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	22 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	58 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Ethnicity (NIH/OMB) EMPOWER Study (randomized) · Not Hispanic or Latino	174 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	152 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	159 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	485 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Ethnicity (NIH/OMB) EMPOWER Study (randomized) · Unknown or Not Reported	5 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	4 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	10 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	19 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Ethnicity (NIH/OMB) VALUE Study (non-randomized) · Hispanic or Latino	—	—	—	43 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	43 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Ethnicity (NIH/OMB) VALUE Study (non-randomized) · Not Hispanic or Latino	—	—	—	756 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	756 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Ethnicity (NIH/OMB) VALUE Study (non-randomized) · Unknown or Not Reported	—	—	—	11 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	11 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) EMPOWER Study (randomized) · American Indian or Alaska Native	0 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	0 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) EMPOWER Study (randomized) · Asian	3 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	4 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	7 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) EMPOWER Study (randomized) · Native Hawaiian or Other Pacific Islander	0 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	0 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) EMPOWER Study (randomized) · Black or African American	9 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	10 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	7 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	26 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) EMPOWER Study (randomized) · White	154 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	127 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	150 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	431 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) EMPOWER Study (randomized) · More than one race	14 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	11 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	8 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	33 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) EMPOWER Study (randomized) · Unknown or Not Reported	23 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	16 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	26 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	65 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) VALUE Study (non-randomized) · American Indian or Alaska Native	—	—	—	0 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) VALUE Study (non-randomized) · Asian	—	—	—	4 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	4 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) VALUE Study (non-randomized) · Native Hawaiian or Other Pacific Islander	—	—	—	0 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) VALUE Study (non-randomized) · Black or African American	—	—	—	10 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	10 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) VALUE Study (non-randomized) · White	—	—	—	718 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	718 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) VALUE Study (non-randomized) · More than one race	—	—	—	38 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	38 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Race (NIH/OMB) VALUE Study (non-randomized) · Unknown or Not Reported	—	—	—	40 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	40 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration EMPOWER Study (randomized) · 0.5 - 1 year	1 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	2 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	3 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration EMPOWER Study (randomized) · 1 - 5 years	24 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	28 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	32 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	84 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration EMPOWER Study (randomized) · 6 - 10 years	25 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	26 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	23 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	74 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration EMPOWER Study (randomized) · 10 - 20 years	76 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	57 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	68 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	201 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration EMPOWER Study (randomized) · > 20 years	76 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	57 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	66 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	199 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration EMPOWER Study (randomized) · Unknown or not reported	1 Participants n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0 Participants n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	1 Participants n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration VALUE Study (non-randomized) · 0.5 - 1 year	—	—	—	7 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	7 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration VALUE Study (non-randomized) · 1 - 5 years	—	—	—	48 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	48 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration VALUE Study (non-randomized) · 6 - 10 years	—	—	—	145 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	145 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration VALUE Study (non-randomized) · 10 - 20 years	—	—	—	301 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	301 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration VALUE Study (non-randomized) · > 20 years	—	—	—	302 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	302 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Duration VALUE Study (non-randomized) · Unknown or not reported	—	—	—	7 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	7 Participants n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Intensity - Average EMPOWER Study (randomized)	6.2 units on a scale STANDARD_DEVIATION 1.9 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	6.2 units on a scale STANDARD_DEVIATION 1.9 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	6.2 units on a scale STANDARD_DEVIATION 1.9 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	6.2 units on a scale STANDARD_DEVIATION 1.9 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Intensity - Average VALUE Study (non-randomized)	—	—	—	6.1 units on a scale STANDARD_DEVIATION 1.8 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	6.1 units on a scale STANDARD_DEVIATION 1.8 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Morphine Equivalent Daily Dose (MEDD) EMPOWER Study (randomized)	141.6 MEDD STANDARD_DEVIATION 280.0 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	123.4 MEDD STANDARD_DEVIATION 263.0 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	109.1 MEDD STANDARD_DEVIATION 167.0 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	125.1 MEDD STANDARD_DEVIATION 242.0 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Morphine Equivalent Daily Dose (MEDD) VALUE Study (non-randomized)	—	—	—	116 MEDD STANDARD_DEVIATION 194 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	116 MEDD STANDARD_DEVIATION 194 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Catastrophizing Scale EMPOWER Study (randomized)	20.8 score on a scale STANDARD_DEVIATION 11.6 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	22.8 score on a scale STANDARD_DEVIATION 11.9 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	21.6 score on a scale STANDARD_DEVIATION 11.5 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	21.7 score on a scale STANDARD_DEVIATION 11.7 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Catastrophizing Scale VALUE Study (non-randomized)	—	—	—	32.4 score on a scale STANDARD_DEVIATION 12.0 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	32.4 score on a scale STANDARD_DEVIATION 12.0 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Brief Pain Inventory (BPI) - Pain Interference EMPOWER Study (randomized)	5.9 units on a scale STANDARD_DEVIATION 2.4 • n=203 Participants • Different measure was used to assess pain interference in the VALUE study. Data from the two studies (EMPOWER and VALUE) were analyzed separately.	5.8 units on a scale STANDARD_DEVIATION 2.3 • n=168 Participants • Different measure was used to assess pain interference in the VALUE study. Data from the two studies (EMPOWER and VALUE) were analyzed separately.	6.1 units on a scale STANDARD_DEVIATION 2.2 • n=191 Participants • Different measure was used to assess pain interference in the VALUE study. Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	5.9 units on a scale STANDARD_DEVIATION 2.3 • n=562 Participants • Different measure was used to assess pain interference in the VALUE study. Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Pain Interference VALUE Study (non-randomized)	—	—	—	68.1 score on a scale STANDARD_DEVIATION 6.0 • n=810 Participants • Different measure was used in the EMPOWER study to assess for pain interference. Data from the two studies (EMPOWER and VALUE) were analyzed separately.	68.1 score on a scale STANDARD_DEVIATION 6.0 • n=810 Participants • Different measure was used in the EMPOWER study to assess for pain interference. Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Self-Efficacy EMPOWER Study (randomized)	6.2 units on a scale STANDARD_DEVIATION 3.6 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	6.6 units on a scale STANDARD_DEVIATION 3.3 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	6.7 units on a scale STANDARD_DEVIATION 3.4 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	6.5 units on a scale STANDARD_DEVIATION 3.4 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Pain Self-Efficacy VALUE Study (non-randomized)	—	—	—	5.4 units on a scale STANDARD_DEVIATION 3.4 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	5.4 units on a scale STANDARD_DEVIATION 3.4 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Anger EMPOWER Study (randomized)	49.9 score on a scale STANDARD_DEVIATION 9.4 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	49.9 score on a scale STANDARD_DEVIATION 8.9 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	51.3 score on a scale STANDARD_DEVIATION 9.0 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	50.4 score on a scale STANDARD_DEVIATION 9.1 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Anger VALUE Study (non-randomized)	—	—	—	49.3 score on a scale STANDARD_DEVIATION 9.3 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	49.3 score on a scale STANDARD_DEVIATION 9.3 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Anxiety EMPOWER Study (randomized)	54.6 score on a scale STANDARD_DEVIATION 9.7 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	54.5 score on a scale STANDARD_DEVIATION 9.5 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	55.9 score on a scale STANDARD_DEVIATION 9.4 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	55.0 score on a scale STANDARD_DEVIATION 9.6 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Anxiety VALUE Study (non-randomized)	—	—	—	53.0 score on a scale STANDARD_DEVIATION 9.1 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	53.0 score on a scale STANDARD_DEVIATION 9.1 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Cognitive Function EMPOWER Study (randomized)	53.6 score on a scale STANDARD_DEVIATION 10.4 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	54.4 score on a scale STANDARD_DEVIATION 9.9 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	55.4 score on a scale STANDARD_DEVIATION 9.7 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	54.5 score on a scale STANDARD_DEVIATION 10.0 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Cognitive Function VALUE Study (non-randomized)	—	—	—	53.2 score on a scale STANDARD_DEVIATION 10.0 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	53.2 score on a scale STANDARD_DEVIATION 10.0 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Physical Function EMPOWER Study (randomized)	64.8 score on a scale STANDARD_DEVIATION 6.5 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	63.9 score on a scale STANDARD_DEVIATION 6.1 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	64.4 score on a scale STANDARD_DEVIATION 6.5 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	64.4 score on a scale STANDARD_DEVIATION 6.4 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Physical Function VALUE Study (non-randomized)	—	—	—	65.4 score on a scale STANDARD_DEVIATION 5.3 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	65.4 score on a scale STANDARD_DEVIATION 5.3 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Fatigue EMPOWER Study (randomized)	57.7 score on a scale STANDARD_DEVIATION 10.0 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	56.8 score on a scale STANDARD_DEVIATION 9.3 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	58.2 score on a scale STANDARD_DEVIATION 9.6 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	57.6 score on a scale STANDARD_DEVIATION 9.7 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Fatigue VALUE Study (non-randomized)	—	—	—	60.3 score on a scale STANDARD_DEVIATION 9.8 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	60.3 score on a scale STANDARD_DEVIATION 9.8 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Sleep Disturbance EMPOWER Study (randomized)	57.4 score on a scale STANDARD_DEVIATION 8.6 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	55.5 score on a scale STANDARD_DEVIATION 8.8 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	57.4 score on a scale STANDARD_DEVIATION 8.3 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	56.8 score on a scale STANDARD_DEVIATION 8.6 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Sleep Disturbance VALUE Study (non-randomized)	—	—	—	57.2 score on a scale STANDARD_DEVIATION 8.5 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	57.2 score on a scale STANDARD_DEVIATION 8.5 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Social Isolation EMPOWER Study (randomized)	47.4 score on a scale STANDARD_DEVIATION 9.5 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	48.8 score on a scale STANDARD_DEVIATION 9.3 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	48.7 score on a scale STANDARD_DEVIATION 9.7 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	48.3 score on a scale STANDARD_DEVIATION 9.5 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Social Isolation VALUE Study (non-randomized)	—	—	—	48.9 score on a scale STANDARD_DEVIATION 9.3 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	48.9 score on a scale STANDARD_DEVIATION 9.3 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Satisfaction with Social Roles & Activities EMPOWER Study (randomized)	59.8 score on a scale STANDARD_DEVIATION 8.1 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	58.5 score on a scale STANDARD_DEVIATION 7.5 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	60.1 score on a scale STANDARD_DEVIATION 7.7 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	59.5 score on a scale STANDARD_DEVIATION 7.8 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Satisfaction with Social Roles & Activities VALUE Study (non-randomized)	—	—	—	60.4 score on a scale STANDARD_DEVIATION 7.8 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	60.4 score on a scale STANDARD_DEVIATION 7.8 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Depression EMPOWER Study (randomized)	54.8 score on a scale STANDARD_DEVIATION 8.9 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	55.3 score on a scale STANDARD_DEVIATION 8.0 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	55.9 score on a scale STANDARD_DEVIATION 8.8 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	55.3 score on a scale STANDARD_DEVIATION 8.6 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
PROMIS - Depression VALUE Study (non-randomized)	—	—	—	54.6 score on a scale STANDARD_DEVIATION 8.7 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	54.6 score on a scale STANDARD_DEVIATION 8.7 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Alcohol Use Disorders Identification Test (AUDIT) EMPOWER Study (randomized)	0.9 score on a scale STANDARD_DEVIATION 2.3 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	1.3 score on a scale STANDARD_DEVIATION 2.4 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0.9 score on a scale STANDARD_DEVIATION 2.0 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	1.0 score on a scale STANDARD_DEVIATION 2.2 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Alcohol Use Disorders Identification Test (AUDIT) VALUE Study (non-randomized)	—	—	—	1.4 score on a scale STANDARD_DEVIATION 2.1 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	1.4 score on a scale STANDARD_DEVIATION 2.1 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Drug Abuse Screen Test (DAST) EMPOWER Study (randomized)	0.6 score on a scale STANDARD_DEVIATION 1.2 • n=203 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0.6 score on a scale STANDARD_DEVIATION 1.3 • n=168 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	0.5 score on a scale STANDARD_DEVIATION 1.2 • n=191 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	—	0.6 score on a scale STANDARD_DEVIATION 1.2 • n=562 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.
Drug Abuse Screen Test (DAST) VALUE Study (non-randomized)	—	—	—	2.1 score on a scale STANDARD_DEVIATION 1.4 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.	2.1 score on a scale STANDARD_DEVIATION 1.4 • n=810 Participants • Data from the two studies (EMPOWER and VALUE) were analyzed separately.

PRIMARY outcome

Timeframe: Baseline and 12 months

Population: Data from the two studies (EMPOWER and VALUE) were analyzed separately. VALUE study did not have opioid tapering success as an outcome given that the study was observational (there was no opioid tapering implemented as part of the study); therefore, participants in the VALUE study were not assessed for this outcome.

Outcome measures

Outcome measures
Measure	Cognitive Behavioral Therapy for Chronic Pain (Pain-CBT) n=177 Participants A trained psychologist delivers pain-CBT to individual patients or groups of patients with chronic pain. Group treatment is delivered across 8 weekly sessions that last for 2 hours each. Pain-CBT incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session. Pain-CBT is effective for reducing pain intensity, pain catastrophizing, depression and social impacts.	Chronic Pain Self Management Program (CPSMP) n=137 Participants The CPSMP is similar to pain-CBT in format and content but is peer-led, and is effective across pain conditions (e.g., back pain, arthritis) for improving pain and pain self-efficacy. The CPSMP consists of six weekly 2-hour group sessions in which two peer co-leaders provide patient education about pain, effective self-management, pain impacts, and other symptoms from a highly structured manual. Peers are people with chronic pain who live in the communities in which they teach. For this project, at least one peer facilitator per workshop will have had experience with prescription opioid use. Intervention fidelity is determined by having a trained observer with a checklist attend random workshop sessions. Similar to pain-CBT, CPSMP incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session.	Taper Only (Usual Care) n=159 Participants Participants allocated to 'Taper Only' will engage in a physician-guided, patient-centered opioid tapering program without additional behavioral intervention.	Observational Arm (The VALUE Study) Participants that do not wish to reduce their opioid medications but are otherwise eligible and interested in the research study will be offered participation in the observational arm. The observational arm of the study will not include interventions of any kind and will only collect survey data for the year following consent.
Opioid Tapering Success	86 Participants	61 Participants	81 Participants	0 Participants

Adverse Events

Cognitive Behavioral Therapy for Chronic Pain (Pain-CBT)

Serious events: 9 serious events

Other events: 162 other events

Deaths: 5 deaths

Chronic Pain Self Management Program (CPSMP)

Serious events: 7 serious events

Other events: 140 other events

Deaths: 1 deaths

Taper Only (Usual Care)

Serious events: 8 serious events

Other events: 159 other events

Deaths: 2 deaths

Observational Arm (the VALUE Study)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Cognitive Behavioral Therapy for Chronic Pain (Pain-CBT) n=203 participants at risk A trained psychologist delivers pain-CBT to individual patients or groups of patients with chronic pain. Group treatment is delivered across 8 weekly sessions that last for 2 hours each. Pain-CBT incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session. Pain-CBT is effective for reducing pain intensity, pain catastrophizing, depression and social impacts.	Chronic Pain Self Management Program (CPSMP) n=168 participants at risk The CPSMP is similar to pain-CBT in format and content but is peer-led, and is effective across pain conditions (e.g., back pain, arthritis) for improving pain and pain self-efficacy. The CPSMP consists of six weekly 2-hour group sessions in which two peer co-leaders provide patient education about pain, effective self-management, pain impacts, and other symptoms from a highly structured manual. Peers are people with chronic pain who live in the communities in which they teach. For this project, at least one peer facilitator per workshop will have had experience with prescription opioid use. Intervention fidelity is determined by having a trained observer with a checklist attend random workshop sessions. Similar to pain-CBT, CPSMP incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session.	Taper Only (Usual Care) n=191 participants at risk Participants allocated to 'Taper Only' will engage in a physician-guided, patient-centered opioid tapering program without additional behavioral intervention.	Observational Arm (the VALUE Study) n=810 participants at risk Participants that do not wish to reduce their opioid medications but are otherwise eligible and interested in the research study will be offered participation in the observational arm. The observational arm of the study will not include interventions of any kind and will only collect survey data for the year following consent.
General disorders Emergency room visit	15.3% 31/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	11.9% 20/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	17.3% 33/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Nervous system disorders Medical history - chronic pain	16.3% 33/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	36.3% 61/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	13.6% 26/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
General disorders New medical issue	33.5% 68/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	20.8% 35/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	23.0% 44/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
General disorders Urgent care visit	2.0% 4/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	2.4% 4/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	3.7% 7/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Psychiatric disorders Suicidal ideation	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.52% 1/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
General disorders Subjective Opiate Withdrawal Scale (SOWS)	12.8% 26/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	11.9% 20/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	25.1% 48/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.

Additional Information

Beth Darnall, PhD

Stanford University

Phone: N/A

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cognitive Behavioral Therapy for Chronic Pain (Pain-CBT) n=203 participants at risk A trained psychologist delivers pain-CBT to individual patients or groups of patients with chronic pain. Group treatment is delivered across 8 weekly sessions that last for 2 hours each. Pain-CBT incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session. Pain-CBT is effective for reducing pain intensity, pain catastrophizing, depression and social impacts.	Chronic Pain Self Management Program (CPSMP) n=168 participants at risk The CPSMP is similar to pain-CBT in format and content but is peer-led, and is effective across pain conditions (e.g., back pain, arthritis) for improving pain and pain self-efficacy. The CPSMP consists of six weekly 2-hour group sessions in which two peer co-leaders provide patient education about pain, effective self-management, pain impacts, and other symptoms from a highly structured manual. Peers are people with chronic pain who live in the communities in which they teach. For this project, at least one peer facilitator per workshop will have had experience with prescription opioid use. Intervention fidelity is determined by having a trained observer with a checklist attend random workshop sessions. Similar to pain-CBT, CPSMP incorporates interactive discussion, practice of relaxation training, action planning, and home exercises into each session.	Taper Only (Usual Care) n=191 participants at risk Participants allocated to 'Taper Only' will engage in a physician-guided, patient-centered opioid tapering program without additional behavioral intervention.	Observational Arm (the VALUE Study) n=810 participants at risk Participants that do not wish to reduce their opioid medications but are otherwise eligible and interested in the research study will be offered participation in the observational arm. The observational arm of the study will not include interventions of any kind and will only collect survey data for the year following consent.
Injury, poisoning and procedural complications Car accident	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.60% 1/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Infections and infestations Sepsis	0.49% 1/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.60% 1/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Infections and infestations Urinary tract infection	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.60% 1/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Psychiatric disorders Suicidal ideation	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.60% 1/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.52% 1/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Surgical and medical procedures Surgery - elective	0.99% 2/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.60% 1/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
General disorders Differential diagnosis	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.52% 1/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Cardiac disorders Cardiac issue	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.52% 1/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
General disorders	0.49% 1/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.52% 1/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Musculoskeletal and connective tissue disorders Parkinson's disease	0.49% 1/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Respiratory, thoracic and mediastinal disorders Progressive chronic obstructive pulmonary disease	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.52% 1/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Vascular disorders cerebrovascular accident (stroke)	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	1.6% 3/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Cardiac disorders Decompensated heart failure	0.49% 1/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
General disorders Alcohol use complications	0.49% 1/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer	0.49% 1/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Cardiac disorders Cardiac arrest	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.60% 1/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Renal and urinary disorders Failing kidneys	0.49% 1/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.
Surgical and medical procedures Toe amputation	0.00% 0/203 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.60% 1/168 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/191 • Baseline, Weekly, Month 6, Monthly, and Month 12.	0.00% 0/810 • Baseline, Weekly, Month 6, Monthly, and Month 12.