The BEST Trial: Biomarkers for Evaluating Spine Treatments

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05396014

Acronym

BEST

Enrollment

1014

Registered

2022-05-27

Start date

2022-09-12

Completion date

2024-10-22

Last updated

2025-07-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Low-back Pain

Keywords

Pain, Back Pain

Brief summary

The BEST Trial (Biomarkers for Evaluating Spine Treatments) is a National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)-sponsored clinical trial being conducted through the NIH Helping to End Addiction Long-term (HEAL) Initiative's Back Pain Consortium (BACPAC) Research Program. The primary objective of this trial is to inform a precision medicine approach to the treatment of Chronic Low-Back Pain by estimating the optimal treatment or combination of treatments based on patient features and response to the initial treatment. Interventions being evaluated in this trial are: (1) enhanced self-care (ESC), (2) acceptance and commitment therapy (ACT), (3) evidence-based exercise and manual therapy (EBEM), and (4) duloxetine.

Detailed description

Each participant will complete an initial screening call and enrollment visit, followed by a 2-week run-in period, two consecutive 12-week treatment periods, and a 12-week post-treatment follow-up period. Upon completion of the run-in period, participant eligibility will be reassessed based on adherence to study protocol. Participants who no longer meet eligibility criteria will be considered screen failures and discontinued from the study. All participants will undergo phenotyping assessments at Visit 0, 1 and 2 corresponding to baseline, the end of the first 12-week intervention period, and the end of the second 12-week intervention period, respectively. A subset of participants will undergo additional phenotyping, consisting of a more comprehensive set of phenotyping assessments, at the same visits. Pain, Enjoyment of Life, and General Activity (PEG) and Patient Global Impressions Scale (PGIC) will be assessed at 6 weeks (midpoint of intervention period one), 12 weeks (Visit 1), 18 weeks (midpoint of intervention period two), 24 weeks (Visit 2), and 36 weeks post-baseline (12 weeks after intervention period two). Basic safety assessments will also be performed at these time points to assess participant tolerability to their current study intervention(s). Patients who are unable to tolerate their assigned study treatment will be educated on how to safely discontinue their current treatment plan but will otherwise remain in the study.

Interventions

BEHAVIORALEnhanced Self-Care (ESC)

The Enhanced Self-Care intervention will be comprised of educational modules on evidence-based cognitive-behavioral self-management skills for pain. These modules will be provided digitally for self-administration over a period of 12 weeks. There will be no therapist associated with the delivery of these educational materials; however, after the first four modules, email or text messages will be used to make personalized recommendations for accessing additional modules based upon identified problems from the baseline assessment. Additionally, the walking program module will utilize Fitbit step tracking to allow participants to monitor their walking progress.

BEHAVIORALAcceptance and Commitment Therapy (ACT)

ACT is a form of cognitive behavioral therapy that is well established for the treatment of chronic pain. The goal of ACT is to build psychological flexibility thereby interrupting pain avoidance behavior patterns. Participants randomized to ACT will take part in 12 sessions over the course of 12 weeks. Sessions will be delivered as a combination of 4 remote face-to-face visits with a therapist and 8 therapist-supported online sessions (self-directed online modules supported by provider coaching). Online sessions will focus on helping participants accept pain, connect with negative thoughts and emotions, develop mindfulness and identify and commit to values and goals that are important to them. During face-to-face sessions with the therapist, participants will be encouraged to share their experience of skills practice and mastery, provide examples of skill use at home, and describe what barriers they encountered.

BEHAVIORALEvidence-Based Exercise and Manual Therapy (EBEM)

Licensed physical therapists (PTs) or Doctors of Chiropractic (DCs) will rely on evidence-based guidance to direct decision-making on the particular type of manual and exercise therapy that may be best suited to an individual study participant. Special attention will be paid to the clinician's choice of language in regard to the purpose and expected outcomes of manual therapy in order to avoid enhancing catastrophizing ideations or preference for passive interventions. A total of 10 sessions will be provided over an 8-week treatment period. Two sessions per week are provided in the first two weeks followed by weekly sessions over the next 6 weeks. Treatment sessions will last approximately 60 minutes each.

DRUGDuloxetine

Duloxetine is a serotonin norepinephrine reuptake inhibitor (SNRI) that is FDA-approved for use in Chronic Low-Back Pain, and, as such, is included as a recommended therapy in nearly all current treatment guidelines for low back pain. Study participants will be treated with duloxetine for 12 weeks during the active treatment phase. At the time of randomization, the approved drug pharmacy at each study site will dispense between 185 and 192 duloxetine 30 mg capsules and provide to participants. This will ensure enough capsules to maintain up to a 60 mg dosage through the 12-week intervention phase and to taper the dose in the 13th week if needed.

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Intervention model description

Sequential Multiple Assignment Randomized Trial (SMART)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

To be eligible, an individual must meet all of the following inclusion criteria: * Ability to read and understand English * Provision of signed and dated informed consent form(s) * Willing and able to receive study-related messages and survey links via email * Willing and able to receive study-related phone calls * Age 18 years old or older * Low-back pain for at least 3 months and occurring on at least half the days in the past 6 months * Contraindicated to no more than one of the study interventions at the time of eligibility assessment(s) * Eligible to receive at least three of the four study interventions and willing to receive any intervention for which they are eligible * A PEG score 4 or higher prior to the Run-in period * Willing and able to undergo required phenotyping * Regular reliable access to an internet-enabled device such as a smart phone, tablet, or laptop computer * Meet Run-in period engagement eligibility criteria: o Completion of two Run-in study information modules prior to period 1 randomization (Visit 0) * Low-back pain more severe than pain in other parts of the body * Available to complete the full study protocol (approximately 9 months)

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study: * Pregnant at the time of Visit 0 (Baseline) * Affirmative participant response to any of the following conditions: * Progressive neurodegenerative disease * History of discitis osteomyelitis (spine infection) or spine tumor * History of ankylosing spondylitis, rheumatoid arthritis, polymyalgia rheumatica, psoriatic arthritis, or lupus * History of cauda equina syndrome or spinal radiculopathy with functional motor deficit (strength \<4/5 on manual motor testing) * Diagnosis of any vertebral fracture in the last 6 months * Osteoporosis requiring pharmacologic treatment other than vitamin D, calcium supplements, or bisphosphonates. * History of any bone-related cancer or cancer that metastasized to the bone * Currently in treatment for any non-skin cancer or plan to start non-skin cancer treatment in the next 12 months * History of any non-skin cancer treatment in the last 24 months * Visual or hearing difficulties that would preclude participation * Uncontrolled drug/alcohol addiction * Individuals actively pursuing disability or workers compensation or involved in active personal injury-related litigation * Currently participating in another interventional pain study * Any condition that, in the opinion of the investigator, would preclude the patient from being able to safely participate in in the trial

Design outcomes

Primary

Measure	Time frame	Description
Patient-Reported Pain Intensity and Interference Score	Baseline, 24 Weeks	Patient-reported pain intensity and interference is measured by the Pain, Enjoyment of Life, and General Activity (PEG) scale. The PEG is a series of 3 questions. Results range from -10 to 10, with higher scores indicating increased pain intensity and interference at 24 Weeks compared to Baseline.

Secondary

Measure	Time frame	Description
Number of Participants Self-Reporting Taking Opioids	24 Weeks	The number of participants self-reporting taking opioids (Yes response) is measured by a single question, Are you currently taking any opioid pain medication on a daily basis?.
Patient-Reported Outcomes Measurement Information System- Physical Function	Baseline, 24 Weeks	Physical function is measured by the Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) Short Form 6b. The PROMIS-PF Short Form 6b is a series of 6 questions. T-scores range from 21.6 to 58.7 and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -37.1 to 37.1, with higher physical function scores indicating a better outcome and increased physical functioning at 24 Weeks compared to Baseline. A higher physical function is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Score	Baseline, 24 Weeks	Depression score is measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) 4-item depression scale from the PROMIS 29 profile. The PROMIS 4-item depression scale from the PROMIS 29 profile is a series of 4 questions. T-scores range from 41.0 to 79.4), and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -38.4 to 38.4, with higher scores indicating increased depression at 24 Weeks compared to Baseline. A lower depression score is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Patient-Reported Outcomes Measurement Information System-Pain Interference	Baseline, 24 Weeks	Pain interference is measured by the 4-item PROMIS (Patient-Reported Outcomes Measurement Information System) Pain Interference scale (PROMIS-PI, 4a). The PROMIS-PI, 4a is a series of 4 questions, and measures self-reported consequences of pain on relevant aspects of one's life. Results range from -34 to 34 (t-scores range from 41.6 to 75.6). For each t-score, 50 indicates the population mean with a standard deviation of 10. Lower scores indicate lower pain interference and a better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.
Patient-Reported Outcomes Measurement Information System - Sleep Disturbance	Baseline, 24 Weeks	Sleep disturbance is measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) short form 6a. The PROMIS short form 6a is a series of 6 questions. T-scores range from 31.7 to 76.1 and for each t-score, 50 indicates the population mean with a standard deviation of 10). Results range from -44.4 to 44.4, with higher scores indicating increased sleep disturbance at 24 Weeks compared to Baseline. A lower sleep disturbance score is the better outcome. PPROMIS measures are not used for clinical decision making but to describe participant symptoms.
Sleep Duration	Baseline, 24 Weeks	Sleep duration is measured by the Back Pain Consortium (BACPAC) sleep duration question, During the past month, how many hours and minutes of actual sleep did you get at night? (This may be different than the number of hours and minutes you spent in bed). Participants respond with a number of hours and minutes. Results range from -24 to 24 hours, with higher number of hours indicating increased sleep duration at 24 Weeks compared to Baseline.
Patient-Reported Outcomes Measurement Information System-Emotional Distress-Anxiety	Baseline, 24 Weeks	Anxiety score is measured by the Patient-Reported Outcomes Measurement Information System-Emotional Distress-Anxiety (PROMIS-EDA) scale 4a. The PROMIS-EDA 4a is a series of 4 questions. T-scores range from 40.3 to 81.6, and for each t-score, 50 indicates the population mean with a standard deviation of 10. Results range from -41.3 to 41.3, with higher scores indicating increased anxiety at 24 Weeks compared to Baseline. A lower anxiety score is the better outcome. PROMIS measures are not used for clinical decision making but to describe participant symptoms.

Countries

United States

Participant flow

Pre-assignment details

While 1014 participants in total were enrolled in the trial, 805 were randomized. This was due to participant withdrawal or participant ineligibility during the run-in period between the enrollment visit and randomization.

Participants by arm

Arm	Count
Stage 1: Acceptance and Commitment Therapy (ACT) ACT is a form of cognitive behavioral therapy that is well established for the treatment of chronic pain. The goal of ACT is to build psychological flexibility thereby interrupting pain avoidance behavior patterns. Participants randomized to ACT will take part in 12 sessions over the course of 12 weeks. Sessions will be delivered as a combination of 4 remote face-to-face visits with a therapist and 8 therapist-supported online sessions (self-directed online modules supported by provider coaching). Online sessions will focus on helping participants accept pain, connect with negative thoughts and emotions, develop mindfulness and identify and commit to values and goals that are important to them. During face-to-face sessions with the therapist, participants will be encouraged to share their experience of skills practice and mastery, provide examples of skill use at home, and describe what barriers they encountered.	203
Stage 1: Duloxetine Duloxetine is a serotonin norepinephrine reuptake inhibitor (SNRI) that is FDA-approved for use in Chronic Low-Back Pain, and, as such, is included as a recommended therapy in nearly all current treatment guidelines for low back pain. Study participants will be treated with duloxetine for 12 weeks during the active treatment phase. At the time of randomization, the approved drug pharmacy at each study site will dispense between 185 and 192 duloxetine 30 mg capsules and provide to participants. This will ensure enough capsules to maintain up to a 60 mg dosage through the 12-week intervention phase and to taper the dose in the 13th week if needed.	198
Stage 1: Evidence Based Exercise and Manual Therapy (EBEM) Licensed physical therapists (PTs) or Doctors of Chiropractic (DCs) will rely on evidence-based guidance to direct decision-making on the particular type of manual and exercise therapy that may be best suited to an individual study participant. Special attention will be paid to the clinician's choice of language in regard to the purpose and expected outcomes of manual therapy in order to avoid enhancing catastrophizing ideations or preference for passive interventions. A total of 10 sessions will be provided over an 8-week treatment period. Two sessions per week are provided in the first two weeks followed by weekly sessions over the next 6 weeks. Treatment sessions will last approximately 60 minutes each.	199
Stage 1: Enhanced Self-Care Therapy (ESC) The Enhanced Self-Care intervention will be comprised of educational modules on evidence-based cognitive-behavioral self-management skills for pain. These modules will be provided digitally for self-administration over a period of 12 weeks. There will be no therapist associated with the delivery of these educational materials; however, after the first four modules, email or text messages will be used to make personalized recommendations for accessing additional modules based upon identified problems from the baseline assessment. Additionally, the walking program module will utilize Fitbit step tracking to allow participants to monitor their walking progress.	205
Total	805

Withdrawals & dropouts

Period	Reason	FG000	FG003	FG005	FG006	FG008	FG009	FG013	FG015	FG016	FG017	FG018	FG021	FG022	FG023	FG024	FG025	FG026	FG027	FG030	FG031	FG032	FG034	FG035	FG039	FG040	FG041	FG042
Stage 1 Intervention (Weeks 0-12)	Adverse Event	2	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	1	0	0	0
Stage 1 Intervention (Weeks 0-12)	Lost to Follow-up	15	0	0	0	0	0	8	0	0	0	0	0	0	0	0	0	8	0	0	0	0	0	0	14	0	0	0
Stage 1 Intervention (Weeks 0-12)	Physician Decision	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Stage 1 Intervention (Weeks 0-12)	Protocol Violation	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0
Stage 1 Intervention (Weeks 0-12)	Withdrawal by Subject	18	0	0	0	0	0	13	0	0	0	0	0	0	0	0	0	14	0	0	0	0	0	0	14	0	0	0
Stage 2 Intervention (Weeks 12-24)	Adverse Event	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	1
Stage 2 Intervention (Weeks 12-24)	Lost to Follow-up	0	2	1	1	2	1	0	1	0	0	0	0	1	1	1	2	0	0	1	1	0	1	0	0	3	2	1
Stage 2 Intervention (Weeks 12-24)	Protocol Violation	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Stage 2 Intervention (Weeks 12-24)	Withdrawal by Subject	0	0	0	1	2	0	1	0	1	1	1	1	2	0	1	1	1	1	0	1	1	1	2	0	1	3	1
Stage 2 Screening (Week 12 Pre-Rand.)	Adverse Event	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Stage 2 Screening (Week 12 Pre-Rand.)	Lost to Follow-up	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Stage 2 Screening (Week 12 Pre-Rand.)	Physician Decision	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Stage 2 Screening (Week 12 Pre-Rand.)	Withdrawal by Subject	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline characteristics

Characteristic	Stage 1: Acceptance and Commitment Therapy (ACT)	Stage 1: Enhanced Self-Care Therapy (ESC)	Stage 1: Evidence Based Exercise and Manual Therapy (EBEM)	Total	Stage 1: Duloxetine
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	37 Participants	41 Participants	38 Participants	154 Participants	38 Participants
Age, Categorical Between 18 and 65 years	166 Participants	164 Participants	161 Participants	651 Participants	160 Participants
Age, Continuous	49.4 years STANDARD_DEVIATION 16.5	51.2 years STANDARD_DEVIATION 16.1	49.5 years STANDARD_DEVIATION 16.3	50.4 years STANDARD_DEVIATION 16.1	51.6 years STANDARD_DEVIATION 15.4
Annual household income from all sources $100,000 to $149,999	31 Participants	39 Participants	34 Participants	128 Participants	24 Participants
Annual household income from all sources $10,000 to $24,999	20 Participants	23 Participants	16 Participants	73 Participants	14 Participants
Annual household income from all sources $150,000 to $199,999	17 Participants	6 Participants	14 Participants	58 Participants	21 Participants
Annual household income from all sources $200,000 or more	22 Participants	20 Participants	20 Participants	101 Participants	39 Participants
Annual household income from all sources $25,000 to $34,999	15 Participants	16 Participants	15 Participants	57 Participants	11 Participants
Annual household income from all sources $35,000 to $49,999	15 Participants	13 Participants	21 Participants	64 Participants	15 Participants
Annual household income from all sources $50,000 to $74,999	24 Participants	20 Participants	25 Participants	90 Participants	21 Participants
Annual household income from all sources $75,000 to $99,999	21 Participants	28 Participants	22 Participants	90 Participants	19 Participants
Annual household income from all sources Less than $10,000	11 Participants	12 Participants	9 Participants	36 Participants	4 Participants
Annual household income from all sources Missing	27 Participants	28 Participants	23 Participants	108 Participants	30 Participants
Annual household income from all sources Prefer not to answer	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Any back operations involve a spinal fusion No	15 Participants	20 Participants	13 Participants	61 Participants	13 Participants
Any back operations involve a spinal fusion Not Sure	3 Participants	3 Participants	2 Participants	10 Participants	2 Participants
Any back operations involve a spinal fusion Yes	7 Participants	10 Participants	7 Participants	33 Participants	9 Participants
BMI	28.8 kg/m^2 STANDARD_DEVIATION 6.3	29.4 kg/m^2 STANDARD_DEVIATION 6.9	29.0 kg/m^2 STANDARD_DEVIATION 6.3	29.1 kg/m^2 STANDARD_DEVIATION 6.7	29.3 kg/m^2 STANDARD_DEVIATION 7.2
COVID-19 Vaccine No	15 Participants	14 Participants	17 Participants	54 Participants	8 Participants
COVID-19 Vaccine Not Sure	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
COVID-19 Vaccine Prefer Not to Answer	2 Participants	2 Participants	0 Participants	6 Participants	2 Participants
COVID-19 Vaccine Yes	186 Participants	189 Participants	182 Participants	745 Participants	188 Participants
Current Employment Status Full-time employment	102 Participants	84 Participants	112 Participants	399 Participants	101 Participants
Current Employment Status Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Current Employment Status Not employed	64 Participants	83 Participants	60 Participants	279 Participants	72 Participants
Current Employment Status Part-time employment	35 Participants	37 Participants	27 Participants	124 Participants	25 Participants
Currently Taking Opioid Medication (daily) No	192 Participants	192 Participants	190 Participants	764 Participants	190 Participants
Currently Taking Opioid Medication (daily) Not Sure	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Currently Taking Opioid Medication (daily) Yes	11 Participants	13 Participants	9 Participants	41 Participants	8 Participants
Current Relationship Status Divorced or Separated	32 Participants	42 Participants	33 Participants	128 Participants	21 Participants
Current Relationship Status Domestic Partner	13 Participants	10 Participants	17 Participants	52 Participants	12 Participants
Current Relationship Status Married	97 Participants	99 Participants	94 Participants	407 Participants	117 Participants
Current Relationship Status Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Current Relationship Status Never Married	53 Participants	46 Participants	49 Participants	185 Participants	37 Participants
Current Relationship Status Widowed	6 Participants	7 Participants	6 Participants	30 Participants	11 Participants
Diastolic Blood Pressure (mmHg)	78.5 mmHg STANDARD_DEVIATION 10.5	77.7 mmHg STANDARD_DEVIATION 10.1	76.7 mmHg STANDARD_DEVIATION 9.6	77.9 mmHg STANDARD_DEVIATION 10.1	78.7 mmHg STANDARD_DEVIATION 10.2
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants	18 Participants	17 Participants	72 Participants	13 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	172 Participants	187 Participants	178 Participants	719 Participants	182 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants	0 Participants	4 Participants	14 Participants	3 Participants
Ever applied for, or received, disability insurance for pain condition Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Ever applied for, or received, disability insurance for pain condition No	180 Participants	170 Participants	183 Participants	718 Participants	185 Participants
Ever applied for, or received, disability insurance for pain condition Yes	21 Participants	34 Participants	16 Participants	84 Participants	13 Participants
Ever filed or awarded worker's compensation claim related to back problem Does not apply	16 Participants	23 Participants	17 Participants	69 Participants	13 Participants
Ever filed or awarded worker's compensation claim related to back problem Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Ever filed or awarded worker's compensation claim related to back problem No	179 Participants	174 Participants	175 Participants	704 Participants	176 Participants
Ever filed or awarded worker's compensation claim related to back problem Yes	6 Participants	7 Participants	7 Participants	29 Participants	9 Participants
Ever had low back operation Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Ever had low back operation No	176 Participants	171 Participants	177 Participants	698 Participants	174 Participants
Ever had low back operation Yes, at least one	25 Participants	33 Participants	22 Participants	104 Participants	24 Participants
Ever Hip Replacement Surgery Missing	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ever Hip Replacement Surgery No	196 Participants	196 Participants	190 Participants	773 Participants	191 Participants
Ever Hip Replacement Surgery Yes	7 Participants	9 Participants	9 Participants	32 Participants	7 Participants
Ever Knee Replacement Surgery Missing	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ever Knee Replacement Surgery No	190 Participants	196 Participants	184 Participants	755 Participants	185 Participants
Ever Knee Replacement Surgery Yes	13 Participants	9 Participants	15 Participants	50 Participants	13 Participants
Ever unemployed for 1 or more months due to low back pain Does not apply	16 Participants	27 Participants	21 Participants	84 Participants	20 Participants
Ever unemployed for 1 or more months due to low back pain Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Ever unemployed for 1 or more months due to low back pain No	145 Participants	134 Participants	142 Participants	572 Participants	151 Participants
Ever unemployed for 1 or more months due to low back pain Yes	40 Participants	43 Participants	36 Participants	146 Participants	27 Participants
Fear-Avoidance Beliefs - Physical Activity (FABQ-PA) Score	13.7 units on a scale STANDARD_DEVIATION 5.1	13.4 units on a scale STANDARD_DEVIATION 5.6	13.3 units on a scale STANDARD_DEVIATION 5.2	13.2 units on a scale STANDARD_DEVIATION 5.3	12.3 units on a scale STANDARD_DEVIATION 5.4
Generalized Anxiety Disorder (GAD-2) Raw Score	1.7 units on a scale STANDARD_DEVIATION 1.8	1.4 units on a scale STANDARD_DEVIATION 1.6	1.5 units on a scale STANDARD_DEVIATION 1.7	1.4 units on a scale STANDARD_DEVIATION 1.6	1.1 units on a scale STANDARD_DEVIATION 1.2
General Sensory Sensitivity (GSS) Score - Interoception	0.6 units on a scale STANDARD_DEVIATION 0.8	0.6 units on a scale STANDARD_DEVIATION 0.8	0.6 units on a scale STANDARD_DEVIATION 0.8	0.6 units on a scale STANDARD_DEVIATION 0.8	0.4 units on a scale STANDARD_DEVIATION 0.7
General Sensory Sensitivity (GSS) Score - Total	1.5 units on a scale STANDARD_DEVIATION 1.8	1.5 units on a scale STANDARD_DEVIATION 1.8	1.7 units on a scale STANDARD_DEVIATION 2	1.5 units on a scale STANDARD_DEVIATION 1.8	1.1 units on a scale STANDARD_DEVIATION 1.6
General Sensory Sensitivity Score (GSS) - External	0.9 units on a scale STANDARD_DEVIATION 1.4	0.9 units on a scale STANDARD_DEVIATION 1.3	1.1 units on a scale STANDARD_DEVIATION 1.5	0.9 units on a scale STANDARD_DEVIATION 1.3	0.7 units on a scale STANDARD_DEVIATION 1.2
Headaches in the Past 4 Weeks Bothered a little	95 Participants	103 Participants	92 Participants	386 Participants	96 Participants
Headaches in the Past 4 Weeks Bothered a lot	20 Participants	24 Participants	22 Participants	78 Participants	12 Participants
Headaches in the Past 4 Weeks Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Headaches in the Past 4 Weeks Not bothered at all	86 Participants	77 Participants	85 Participants	338 Participants	90 Participants
Healing Encounters and Attitudes Lists (HEAL) Positive Outlook: Raw Score	21.6 units on a scale STANDARD_DEVIATION 5.6	21.2 units on a scale STANDARD_DEVIATION 5.4	21.6 units on a scale STANDARD_DEVIATION 5.8	21.8 units on a scale STANDARD_DEVIATION 5.4	23.0 units on a scale STANDARD_DEVIATION 4.9
Heart Rate (bpm)	71.7 bpm STANDARD_DEVIATION 12.9	72.8 bpm STANDARD_DEVIATION 12.3	73.2 bpm STANDARD_DEVIATION 12	72.2 bpm STANDARD_DEVIATION 12.2	70.9 bpm STANDARD_DEVIATION 11.6
Highest Level of Education Completed Associate's or Technical Degree Complete	33 Participants	35 Participants	36 Participants	131 Participants	27 Participants
Highest Level of Education Completed College or Baccalaureate Degree Complete	75 Participants	69 Participants	65 Participants	294 Participants	85 Participants
Highest Level of Education Completed Did not complete Secondary School or High School	6 Participants	8 Participants	8 Participants	28 Participants	6 Participants
Highest Level of Education Completed Doctoral or Postgraduate Education	56 Participants	51 Participants	57 Participants	220 Participants	56 Participants
Highest Level of Education Completed High School or Secondary School Degree Complete	31 Participants	41 Participants	33 Participants	129 Participants	24 Participants
Highest Level of Education Completed Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Involved in a lawsuit or legal claim related to back problem Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Involved in a lawsuit or legal claim related to back problem No	199 Participants	201 Participants	198 Participants	794 Participants	196 Participants
Involved in a lawsuit or legal claim related to back problem Not sure	2 Participants	2 Participants	1 Participants	6 Participants	1 Participants
Involved in a lawsuit or legal claim related to back problem Yes	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants
Keele STarT Back Screening Tool Risk High Risk	31 Participants	40 Participants	44 Participants	142 Participants	27 Participants
Keele STarT Back Screening Tool Risk Low Risk	72 Participants	79 Participants	73 Participants	316 Participants	92 Participants
Keele STarT Back Screening Tool Risk Medium Risk	100 Participants	86 Participants	80 Participants	345 Participants	79 Participants
Keele STarT Back Screening Tool Risk Missing	0 Participants	0 Participants	2 Participants	2 Participants	0 Participants
Long COVID No	79 Participants	74 Participants	81 Participants	308 Participants	74 Participants
Long COVID No self-reported COVID-19 diagnosis	91 Participants	101 Participants	92 Participants	384 Participants	100 Participants
Long COVID Not Sure	13 Participants	7 Participants	5 Participants	31 Participants	6 Participants
Long COVID Prefer not to answer	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Long COVID Yes	20 Participants	23 Participants	21 Participants	82 Participants	18 Participants
Low Back Pain Frequency in the past 6 months At least half the days	22 Participants	36 Participants	39 Participants	132 Participants	35 Participants
Low Back Pain Frequency in the past 6 months Every day or nearly every day	181 Participants	169 Participants	160 Participants	673 Participants	163 Participants
Low Back Pain Specific Pain Intensity	5.6 units on a scale STANDARD_DEVIATION 1.9	5.8 units on a scale STANDARD_DEVIATION 1.7	5.6 units on a scale STANDARD_DEVIATION 1.7	5.6 units on a scale STANDARD_DEVIATION 1.8	5.4 units on a scale STANDARD_DEVIATION 1.8
Low Back Pain Specific Pain Intensity, median (range)	5.0 units on a scale	6.0 units on a scale	6.0 units on a scale	6.0 units on a scale	6.0 units on a scale
Number of People Living in Household 1	50 Participants	58 Participants	53 Participants	204 Participants	43 Participants
Number of People Living in Household 2	85 Participants	87 Participants	62 Participants	322 Participants	88 Participants
Number of People Living in Household 3	30 Participants	19 Participants	40 Participants	114 Participants	25 Participants
Number of People Living in Household 4	25 Participants	23 Participants	29 Participants	106 Participants	29 Participants
Number of People Living in Household 5	8 Participants	13 Participants	8 Participants	38 Participants	9 Participants
Number of People Living in Household 6	3 Participants	1 Participants	7 Participants	14 Participants	3 Participants
Number of People Living in Household 7	0 Participants	1 Participants	0 Participants	2 Participants	1 Participants
Number of People Living in Household 8	0 Participants	2 Participants	0 Participants	2 Participants	0 Participants
Number of People Living in Household Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Observed Gait Antalgic	24 Participants	36 Participants	27 Participants	121 Participants	34 Participants
Observed Gait Missing	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Observed Gait Normal	179 Participants	169 Participants	172 Participants	684 Participants	164 Participants
Oswestry Disability Index (ODI) Percentage	29.4 units on a scale STANDARD_DEVIATION 13.5	31.1 units on a scale STANDARD_DEVIATION 14.3	30.7 units on a scale STANDARD_DEVIATION 14.1	29.8 units on a scale STANDARD_DEVIATION 13.6	27.7 units on a scale STANDARD_DEVIATION 12
Oswestry Disability Index (ODI) Percentage, median (range)	28.0 units on a scale	28.9 units on a scale	28.0 units on a scale	28.0 units on a scale	26.7 units on a scale
Pain Catastrophizing Scale - Short Form 6 (PCS-SF6)	11.6 units on a scale STANDARD_DEVIATION 5.3	11.7 units on a scale STANDARD_DEVIATION 5	10.9 units on a scale STANDARD_DEVIATION 4.9	11.1 units on a scale STANDARD_DEVIATION 5	10.4 units on a scale STANDARD_DEVIATION 4.5
Pain Detect Neuropathic Pain Questionnaire (painDETECT) Raw Score Missing	1 Participants	2 Participants	2 Participants	5 Participants	0 Participants
Pain Detect Neuropathic Pain Questionnaire (painDETECT) Raw Score Neuropathic Pain	28 Participants	20 Participants	20 Participants	79 Participants	11 Participants
Pain Detect Neuropathic Pain Questionnaire (painDETECT) Raw Score Nociceptive Pain	136 Participants	147 Participants	142 Participants	579 Participants	154 Participants
Pain Detect Neuropathic Pain Questionnaire (painDETECT) Raw Score Possible Neuropathic Pain	38 Participants	36 Participants	35 Participants	142 Participants	33 Participants
Pain, Enjoyment of Life, General Activity (PEG) score	5.4 units on a scale STANDARD_DEVIATION 2	5.5 units on a scale STANDARD_DEVIATION 1.9	5.3 units on a scale STANDARD_DEVIATION 1.8	5.3 units on a scale STANDARD_DEVIATION 1.9	5.1 units on a scale STANDARD_DEVIATION 1.9
Pain, Enjoyment of Life, General Activity (PEG) score, median (range)	5.3 units on a scale	5.3 units on a scale	5.3 units on a scale	5.3 units on a scale	5.0 units on a scale
Patient Health Questionnaire-2 (PHQ-2): Raw Score	1.6 units on a scale STANDARD_DEVIATION 1.6	1.6 units on a scale STANDARD_DEVIATION 1.6	1.4 units on a scale STANDARD_DEVIATION 1.6	1.5 units on a scale STANDARD_DEVIATION 1.5	1.2 units on a scale STANDARD_DEVIATION 1.2
Perceived Discrimination: Orientation/Gender Identity Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Perceived Discrimination: Orientation/Gender Identity Never	161 Participants	166 Participants	159 Participants	658 Participants	172 Participants
Perceived Discrimination: Orientation/Gender Identity Not sure	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Perceived Discrimination: Orientation/Gender Identity Often to Almost Always	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Perceived Discrimination: Orientation/Gender Identity Rarely	24 Participants	19 Participants	20 Participants	79 Participants	16 Participants
Perceived Discrimination: Orientation/Gender Identity Sometimes	16 Participants	19 Participants	20 Participants	65 Participants	10 Participants
Perceived Discrimination: Race/Ethnicity Missing	3 Participants	1 Participants	0 Participants	4 Participants	0 Participants
Perceived Discrimination: Race/Ethnicity Never	113 Participants	126 Participants	115 Participants	474 Participants	120 Participants
Perceived Discrimination: Race/Ethnicity Not sure	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Perceived Discrimination: Race/Ethnicity Often to Almost Always	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Perceived Discrimination: Race/Ethnicity Rarely	47 Participants	40 Participants	45 Participants	174 Participants	42 Participants
Perceived Discrimination: Race/Ethnicity Sometimes	40 Participants	38 Participants	39 Participants	153 Participants	36 Participants
Previously Diagnosed with Coronavirus Disease 2019 (COVID-19) Missing	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Previously Diagnosed with Coronavirus Disease 2019 (COVID-19) No	84 Participants	98 Participants	85 Participants	362 Participants	95 Participants
Previously Diagnosed with Coronavirus Disease 2019 (COVID-19) Not Sure	4 Participants	1 Participants	5 Participants	15 Participants	5 Participants
Previously Diagnosed with Coronavirus Disease 2019 (COVID-19) Prefer not to answer	3 Participants	2 Participants	2 Participants	7 Participants	0 Participants
Previously Diagnosed with Coronavirus Disease 2019 (COVID-19) Yes	112 Participants	104 Participants	107 Participants	421 Participants	98 Participants
PROMIS Cognitive Function and Abilities - Short Form 2a Raw Score	7.2 units on a scale STANDARD_DEVIATION 1.8	7.2 units on a scale STANDARD_DEVIATION 1.8	7.1 units on a scale STANDARD_DEVIATION 1.8	7.3 units on a scale STANDARD_DEVIATION 1.8	7.5 units on a scale STANDARD_DEVIATION 1.6
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants	3 Participants	1 Participants
Race (NIH/OMB) Asian	23 Participants	19 Participants	17 Participants	80 Participants	21 Participants
Race (NIH/OMB) Black or African American	21 Participants	29 Participants	21 Participants	90 Participants	19 Participants
Race (NIH/OMB) More than one race	6 Participants	8 Participants	7 Participants	27 Participants	6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	2 Participants	0 Participants	3 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants	4 Participants	9 Participants	30 Participants	7 Participants
Race (NIH/OMB) White	142 Participants	142 Participants	144 Participants	572 Participants	144 Participants
Radiating Pain to Below Knee, Past 2 Weeks Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Radiating Pain to Below Knee, Past 2 Weeks No	126 Participants	132 Participants	136 Participants	537 Participants	143 Participants
Radiating Pain to Below Knee, Past 2 Weeks Not Sure	22 Participants	16 Participants	11 Participants	64 Participants	15 Participants
Radiating Pain to Below Knee, Past 2 Weeks Yes	53 Participants	56 Participants	52 Participants	201 Participants	40 Participants
Radiating Pain to Buttock/Thigh, Past 2 Weeks Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Radiating Pain to Buttock/Thigh, Past 2 Weeks No	65 Participants	62 Participants	66 Participants	270 Participants	77 Participants
Radiating Pain to Buttock/Thigh, Past 2 Weeks Not Sure	19 Participants	10 Participants	12 Participants	61 Participants	20 Participants
Radiating Pain to Buttock/Thigh, Past 2 Weeks Yes	117 Participants	132 Participants	121 Participants	471 Participants	101 Participants
Region of Enrollment United States	203 Participants	205 Participants	199 Participants	805 Participants	198 Participants
Self-reported low back pain duration 1-5 years	70 Participants	67 Participants	71 Participants	274 Participants	66 Participants
Self-reported low back pain duration <1 year	12 Participants	15 Participants	9 Participants	50 Participants	14 Participants
Self-reported low back pain duration >5 years	121 Participants	123 Participants	119 Participants	481 Participants	118 Participants
Self-reported low back pain duration Missing	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Self-reported low back pain duration (months)	163.4 months STANDARD_DEVIATION 150	154.7 months STANDARD_DEVIATION 123.4	156.4 months STANDARD_DEVIATION 139.8	157.8 months STANDARD_DEVIATION 141.2	156.7 months STANDARD_DEVIATION 151
Self-reported Sleep Duration in the Past Month (hours)	6.6 hours STANDARD_DEVIATION 1.2	6.6 hours STANDARD_DEVIATION 1.6	6.5 hours STANDARD_DEVIATION 1.2	6.6 hours STANDARD_DEVIATION 1.4	6.7 hours STANDARD_DEVIATION 1.5
Sex: Female, Male Female	116 Participants	134 Participants	131 Participants	496 Participants	115 Participants
Sex: Female, Male Male	87 Participants	71 Participants	68 Participants	309 Participants	83 Participants
Social Determinants of Health: Food Insecurity Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Social Determinants of Health: Food Insecurity Never True	167 Participants	165 Participants	168 Participants	678 Participants	178 Participants
Social Determinants of Health: Food Insecurity Often True	7 Participants	7 Participants	7 Participants	24 Participants	3 Participants
Social Determinants of Health: Food Insecurity Sometimes True	27 Participants	32 Participants	24 Participants	100 Participants	17 Participants
Social Determinants of Health (SDOH): Emotional Support Missing	2 Participants	1 Participants	0 Participants	4 Participants	1 Participants
Social Determinants of Health (SDOH): Emotional Support No	16 Participants	17 Participants	15 Participants	65 Participants	17 Participants
Social Determinants of Health (SDOH): Emotional Support Yes	185 Participants	187 Participants	184 Participants	736 Participants	180 Participants
Social Determinants of Health (SDOH): Food Money Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Social Determinants of Health (SDOH): Food Money Never True	176 Participants	176 Participants	171 Participants	708 Participants	185 Participants
Social Determinants of Health (SDOH): Food Money Often True	5 Participants	6 Participants	7 Participants	22 Participants	4 Participants
Social Determinants of Health (SDOH): Food Money Sometimes True	20 Participants	22 Participants	21 Participants	72 Participants	9 Participants
Social Determinants of Health (SDOH): Healthcare Needs Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Social Determinants of Health (SDOH): Healthcare Needs No	168 Participants	173 Participants	162 Participants	673 Participants	170 Participants
Social Determinants of Health (SDOH): Healthcare Needs Yes	33 Participants	31 Participants	37 Participants	129 Participants	28 Participants
Social Determinants of Health (SDOH): Number of Close Friends 0	1 Participants	2 Participants	6 Participants	17 Participants	8 Participants
Social Determinants of Health (SDOH): Number of Close Friends 1-2	46 Participants	49 Participants	46 Participants	182 Participants	41 Participants
Social Determinants of Health (SDOH): Number of Close Friends 3-5	99 Participants	94 Participants	90 Participants	372 Participants	89 Participants
Social Determinants of Health (SDOH): Number of Close Friends 6-10	36 Participants	48 Participants	40 Participants	164 Participants	40 Participants
Social Determinants of Health (SDOH): Number of Close Friends Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Social Determinants of Health (SDOH): Number of Close Friends More than 10	19 Participants	11 Participants	17 Participants	67 Participants	20 Participants
Social Determinants of Health (SDOH): Stable Housing Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Social Determinants of Health (SDOH): Stable Housing No	187 Participants	188 Participants	187 Participants	754 Participants	192 Participants
Social Determinants of Health (SDOH): Stable Housing Yes	14 Participants	16 Participants	12 Participants	48 Participants	6 Participants
Social Determinants of Health (SDOH): Transportation Needs Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Social Determinants of Health (SDOH): Transportation Needs No	184 Participants	186 Participants	185 Participants	740 Participants	185 Participants
Social Determinants of Health (SDOH): Transportation Needs Yes	17 Participants	18 Participants	14 Participants	62 Participants	13 Participants
Social Determinants of Health (SDOH): Utilities Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Social Determinants of Health (SDOH): Utilities No	196 Participants	193 Participants	193 Participants	771 Participants	189 Participants
Social Determinants of Health (SDOH): Utilities Yes	5 Participants	11 Participants	6 Participants	31 Participants	9 Participants
Stomach Pain in the Past 4 Weeks Bothered a little	71 Participants	77 Participants	78 Participants	292 Participants	66 Participants
Stomach Pain in the Past 4 Weeks Bothered a lot	19 Participants	18 Participants	15 Participants	64 Participants	12 Participants
Stomach Pain in the Past 4 Weeks Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Stomach Pain in the Past 4 Weeks Not bothered at all	111 Participants	109 Participants	106 Participants	446 Participants	120 Participants
Symptom Severity Index	5.5 units on a scale STANDARD_DEVIATION 2.9	5.9 units on a scale STANDARD_DEVIATION 2.7	5.5 units on a scale STANDARD_DEVIATION 2.9	5.5 units on a scale STANDARD_DEVIATION 2.8	4.8 units on a scale STANDARD_DEVIATION 2.4
Systolic Blood Pressure (mmHg)	125.8 mmHg STANDARD_DEVIATION 15.5	125.6 mmHg STANDARD_DEVIATION 13.6	124.2 mmHg STANDARD_DEVIATION 14.3	126.3 mmHg STANDARD_DEVIATION 15.3	129.5 mmHg STANDARD_DEVIATION 17.2
TAPS Alcohol Use At Least Weekly	15 Participants	11 Participants	13 Participants	51 Participants	12 Participants
TAPS Alcohol Use Less Than Monthly	52 Participants	46 Participants	52 Participants	202 Participants	52 Participants
TAPS Alcohol Use Missing	3 Participants	1 Participants	0 Participants	5 Participants	1 Participants
TAPS Alcohol Use Monthly	8 Participants	25 Participants	12 Participants	60 Participants	15 Participants
TAPS Alcohol Use Never	125 Participants	122 Participants	122 Participants	487 Participants	118 Participants
TAPS Drug Use Between Monthly to Weekly	14 Participants	13 Participants	11 Participants	46 Participants	8 Participants
TAPS Drug Use Daily or Almost Daily	11 Participants	11 Participants	8 Participants	35 Participants	5 Participants
TAPS Drug Use Less Than Monthly	11 Participants	22 Participants	13 Participants	63 Participants	17 Participants
TAPS Drug Use Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
TAPS Drug Use Never	165 Participants	158 Participants	167 Participants	658 Participants	168 Participants
TAPS Prescription Drug Used Not as Intended At Least Once	13 Participants	19 Participants	12 Participants	60 Participants	16 Participants
TAPS Prescription Drug Used Not as Intended Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
TAPS Prescription Drug Used Not as Intended Never	188 Participants	185 Participants	187 Participants	742 Participants	182 Participants
TAPS Tobacco Use Daily or Almost Daily	14 Participants	25 Participants	14 Participants	68 Participants	15 Participants
TAPS Tobacco Use Less Than Daily	18 Participants	20 Participants	17 Participants	72 Participants	17 Participants
TAPS Tobacco Use Missing	2 Participants	1 Participants	0 Participants	3 Participants	0 Participants
TAPS Tobacco Use Never	169 Participants	159 Participants	168 Participants	662 Participants	166 Participants
When was last back operation Between 1 and 2 years ago	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
When was last back operation Less than 6 months ago	20 Participants	21 Participants	15 Participants	74 Participants	18 Participants
When was last back operation More than 2 years ago	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
When was last back operation More than 6 months ago but less than 1 year ago	5 Participants	12 Participants	7 Participants	30 Participants	6 Participants
Widespread Pain Inventory: Raw Score	2.3 units on a scale STANDARD_DEVIATION 1.8	2.5 units on a scale STANDARD_DEVIATION 1.7	2.4 units on a scale STANDARD_DEVIATION 1.9	2.3 units on a scale STANDARD_DEVIATION 1.8	2.1 units on a scale STANDARD_DEVIATION 1.8

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk
deaths Total, all-cause mortality	0 / 191	0 / 172	0 / 184	0 / 205	0 / 65	0 / 71	0 / 110	0 / 85	0 / 33	0 / 52	0 / 84	0 / 22	0 / 54	0 / 85
other Total, other adverse events	2 / 191	92 / 172	7 / 184	4 / 205	1 / 65	29 / 71	3 / 110	0 / 85	12 / 33	3 / 52	2 / 84	4 / 22	18 / 54	5 / 85
serious Total, serious adverse events	4 / 191	1 / 172	6 / 184	2 / 205	4 / 65	0 / 71	3 / 110	2 / 85	1 / 33	0 / 52	4 / 84	0 / 22	1 / 54	4 / 85

Outcome results

Primary

Patient-Reported Pain Intensity and Interference Score

Patient-reported pain intensity and interference is measured by the Pain, Enjoyment of Life, and General Activity (PEG) scale. The PEG is a series of 3 questions. Results range from -10 to 10, with higher scores indicating increased pain intensity and interference at 24 Weeks compared to Baseline.

Time frame: Baseline, 24 Weeks