The Design and Rationale of the Biomarkers for Evaluating Spine Treatments (BEST) Trial: A Sequential Multiple Assignment Randomized Trial

Abstract Objective Chronic low back pain (cLBP) is a common condition that impacts quality of life and function. There are many evidence-based treatments to address cLBP; however, treatment effects are modest, perhaps in part due to individual variation in treatment response. The Biomarkers for Evaluating Spine Treatments (BEST) Trial was designed as the collaborative centerpiece of the Back Pain Consortium (BACPAC) research program. This consortium was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) as part of the Helping to End Addiction Long-term (HEAL) Initiative. Design The BEST trial was a sequential, multiple-assignment randomized trial (SMART) designed with the primary goal of identifying in whom different treatments show optimal response. The primary focus of the study was to use patient features, including biomarkers and phenotypic measures, to identify subsets of persons with cLBP who respond best to specific common treatments. Methods Four interventions were chosen for the trial: Enhanced self-care (ESC), acceptance and commitment therapy (ACT), duloxetine, and evidence-based exercise and manual therapy (EBEM). Following a run-in period and baseline assessment, participants were randomized to one of the four treatments for the first 12-week intervention period. Participants were reassessed and based on their self-reported response to initial treatment, continued that initial treatment, were augmented with an additional randomly assigned treatment, or were switched to a new treatment. Conclusion This trial was designed to deliver rich phenotypic data that will both potentially aid in the discovery of phenotypic characteristics that predict treatment response and provide a greater mechanistic understanding of cLBP.