The BEST Trial: Biomarkers for Evaluating Spine Treatments

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 thepast 6 months

• Contraindicated to no more than one of the study interventions at the time ofeligibility assessment(s)

• Eligible to receive at least three of the four study interventions and willing toreceive 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, polymyalgiarheumatica, psoriatic arthritis, or lupus

• History of cauda equina syndrome or spinal radiculopathy with functional motordeficit (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, calciumsupplements, 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 cancertreatment 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 inactive personal injury-related litigation

• Currently participating in another interventional pain study

• Any condition that, in the opinion of the investigator, would preclude the patientfrom being able to safely participate in in the trial