Sequential and Comparative Evaluation of Pain Treatment Effectiveness Response
Sequential and Comparative Evaluation of Pain Treatment Effectiveness Response
Chronic low back pain (cLBP) is common. Most Americans will have at least one episode of low
 back pain in their lifetimes. Approximately 50% of all US Veterans have chronic pain, and
 CLBP is the most common type of pain in this population. This study will use a sequential
 randomized, pragmatic, 2-step comparative effectiveness study design. The main goal is to
 identify the best approach for treating cLBP using commonly recommended non-surgical and
 non-pharmacological options. The first step compares continued care and active monitoring
 (CCAM) to internet-based pain self-management (Pain EASE) and an enhanced physical therapy
 intervention that combines Pain EASE with tailored exercise and physical activity. Patients
 who do not have a significant decrease in pain interference (a functional outcome) in Step 1
 and those desiring additional treatment will be randomized in Step 2 to yoga, spinal
 manipulation therapy (SMT), or therapist-delivered cognitive behavioral therapy (CBT).
 Participants proceeding to randomization in Step 2 will be allowed to exclude up to one of
 the three Step 2 treatments based on their preferences. The investigators' primary hypothesis
 for the first treatment step is that an enhanced physical therapy intervention that combines
 pain self-management education with a tailored exercise program will reduce pain interference
 greater than internet-based pain self-management alone or CCAM in Veterans with cLBP. The
 primary outcome is change in pain interference at 3 months, measured using the Brief Pain
 Inventory (BPI) pain interference subscale. Study participants will be followed for one year
 after initiation of their final study treatments to assess the durability of treatment
 effects. The study plans to randomize 2529 patients across 20 centers.
Chronic low back pain (cLBP) is common. The point prevalence of low back pain in the US is
 about 25%, and the majority of Americans will have at least one episode of low back pain in
 their lifetimes. Approximately 50% of all US Veterans have chronic pain, and cLBP is the most
 common type of pain in this population. Low back pain is the second most common condition
 leading patients to seek a physician's care. In addition, cLBP is costly. Healthcare
 expenditure for low back pain in the US is greater than $30 billion per year, and total
 expenditures including the cost of disability approach $100 billion per year. In fact, low
 back pain is the most common cause of work-related disability and is a major cause of
 service- connected disability amongst US Veterans. Making matters worse, the US is in the
 midst of a growing opioid abuse epidemic having its roots in the lack of understanding of how
 to effectively treat cLBP and other common forms of acute and chronic pain.

 Using a sequential randomized, pragmatic, 2-step comparative effectiveness study design, the
 main goal is to identify the optimal approach to cLBP treatment employing commonly
 recommended non-surgical, non-pharmacological options. Options for treatment in this trial
 were selected based on the VA's stepped-care model for the treatment of chronic pain,
 availability of treatments, controversies in current clinical practice, and the surveyed
 preferences of both Veterans with cLBP and VA healthcare providers. The implementation of
 study results has been kept closely in mind, and stakeholder input has been incorporated.

 The first step compares continued care and active monitoring arm (CCAM) to internet-based
 pain self-management (Pain EASE) and an enhanced physical therapy intervention that combines
 Pain EASE with tailored exercise and physical activity. The utility of tailored exercise
 requiring physical therapist guidance added to internet-based self-management has not been
 examined. A CCAM arm is included in this step to definitively assess the effectiveness of
 these initial treatment options. Patients failing to achieve clinically significant
 reductions in pain interference (a functional outcome) in Step 1 and those desiring
 additional treatment will be randomized in Step 2 to yoga, spinal manipulation therapy (SMT),
 or therapist-delivered cognitive behavioral therapy (CBT). These options appear in consensus
 guidelines although little information is available to help patients and providers select the
 most effective option. Each option has a distinct theoretical basis for effectiveness with
 yoga described as a mind-body therapy, SMT as a technique to adjust the structural
 relationships of the spine, and CBT as a psychological or behavioral approach. While the
 literature suggests approximate clinical equipoise between these treatments, costs, side
 effects, access to specific options and patient/provider acceptance may differ significantly.
 Participants proceeding to randomization in Step 2 will be allowed to exclude up to one of
 the three Step 2 treatments based on their preferences.

 The investigators' primary hypothesis corresponding to the first treatment step is that an
 enhanced physical therapy intervention that combines pain self-management education with a
 tailored exercise program will reduce pain interference greater than internet-based pain
 self-management alone or CCAM in Veterans with cLBP. For the second step, the study has been
 powered to detect clinically meaningful pairwise differences among the three treatments. The
 primary outcome is change in pain interference at 3 months, measured using the Brief Pain
 Inventory (BPI) pain interference subscale. This is a widely accepted functional outcome in
 musculoskeletal pain trials and emphasizes an endpoint important to patients, providers and
 healthcare management systems. Study participants will be followed for one year after
 initiation of their final study treatments to assess the durability of treatment effects.

 The investigators will leverage the power of this large study and maximize its impact by
 incorporating additional outcome measures as recommended by the Initiative on Methods,
 Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consortium and other pain
 trials consensus groups. These secondary outcomes include pain severity, physical
 functioning, depression, anxiety, fatigue, sleep, global impression of change, and quality of
 life. The investigators will evaluate the impact of patient characteristics, treatment
 preferences and expectations on study outcomes as these variables have been identified in
 smaller studies to modify treatment response. To derive information rapidly translatable to
 changes in VA care, the investigators will collect information critical for implementation of
 the treatment strategies under study. Key implementation factors will include treatment
 fidelity, treatment adherence, patient acceptance, provider acceptance, logistical
 feasibility, and resource requirements. Finally, a carefully designed costs and downstream
 budget impact aim will provide additional practical information for clinical managers and
 policy makers related to non-pharmacological treatments for cLBP.

 The study will involve diverse VA centers with respect to geographical region, racial
 characteristics of the population served and facility size. The study plans to randomize 2529
 patients across 20 centers. Preliminary site surveys indicate a high level of enthusiasm for
 the project. In addition, a query of the VA's Corporate Data Warehouse (CDW) identified more
 than 850,000 potential cLBP study subjects receiving regular care through VA. Twenty-five VA
 medical centers have more than 10,000 potentially eligible patients underscoring the high
 prevalence of cLBP. The investigators' pragmatic trial design will incorporate broad
 eligibility criteria.

 Chronic low back pain is an enormous problem for the VA, the United States and many other
 countries. This study will provide definitive information concerning the effectiveness,
 costs, acceptability, and implementation of several commonly used, patient-preferred,
 non-pharmacological treatment options. All the selected treatment options carry relatively
 low levels of risk, are guideline congruent, and are consistent with stepped-care models of
 healthcare delivery used by the VA and other healthcare organizations. The impact on VA
 healthcare is expected to be large and immediate.
Inclusion Criteria:

 To be eligible to participate in this study, an individual must meet all the following
 criteria:

 1. Chronic low back pain current and present for at least 6 months;

 2. Moderate-severe average daily back pain severity (Numeric Rating Scale (NRS) greater
 than or equal to 4 and no greater than 10);

 3. Moderate-severe pain-related disability (Roland Morris Disability Questionnaire score
 greater than or equal to 7);

 4. Age 18 years or older, either sex, any racial or ethnic background;

 5. Able to comprehend and willing to sign the study informed consent form;

 6. Able to attend in-person treatment sessions;

 7. Anticipate continuing care at the enrolling VA for the period of the study;

 8. Stable access to the internet at home, work, or other location (e.g. mobile phone).

 Exclusion Criteria:

 An individual who meets any of the following criteria will be excluded from participation
 in this study:

 1. Currently enrolled in any other interventional study unless exempted by CSP;

 2. Acute or chronic illness that would prevent the Veteran from receiving study
 treatments offered (e.g., uncontrolled hypertension, recent myocardial infarction
 within the last 6 months, unstable angina, acute congestive heart failure);

 3. Neurological impairment related to disease of the spine or other causes preventing
 participation in any of the treatment modalities under study;

 4. Current or recent (last 3 months) treatment involving Cognitive Behavioral Therapy,
 Spinal manipulation therapy, or Yoga;

 5. Current severe alcohol or substance abuse use disorder;

 6. Severe psychiatric illness (e.g. current psychosis, current suicidal ideation, or
 psychiatric illness requiring hospitalization within the last 6 months);

 7. Undergoing evaluation for back surgery or planned back surgery;

 8. Cognitive or severe hearing or visual impairment preventing participation in treatment
 options or outcome measure assessments;

 9. Pregnancy;

 10. Refusal to provide written consent.