The Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION): registry overview and protocol for a propensity score-matched study of opioid prescribing in patients with low back pain

Background: Low back pain is the leading cause of disability worldwide. Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as the first-line pharmaco logic therapy for subacute or chronic low back pain, with opioids reserved for patients who fail on NSAIDs. CYP2D6, CYP2C9, and CYP2C19 genes have variants that place patients using analgesics at risk for adverse events. However, precision medicine based on pharmacogenetically informed prescribing is becoming more feasible as genotyping costs decline. This study aims to compare opioids vs NSAI Ds in treating adults with subacute or chronic low back pain under the alternative models of usual care and precision medicine. Methods: An observational cohort study within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION) will be used to simulate a randomized controlled trial. Patients using opioids and NSAIDs will be optimally matched at baseline using propensity scores. A saliva sample will also be collected to determine patient genotypes for drug metabolism based on CYP2D6 (single-gene model) and CYP2D6, CYP2C9, and CYP2C19 (multigene model). Prescribing that is concordant with pharmacogenetically informed care under these models will be considered "low risk", whereas discordant prescribing will be considered "high risk". Primary outcomes will be assessed over 6 months using a Numerical Rating Scale for pain, the Roland-Morris Disability Questionnaire, and the Drug Adverse Events Index. Secondary outcomes will be assessed using quality-of-life measures. An estimated 600 patients will be enrolled to acquire at least 400 patients after attrition and allowing for unmatched patients. This will achieve a statistical power of at least 80% in detecting the effect sizes ranging from 0.35 (small-medium effect) to 0.69 (medium-large effect). Discussion: This PRECISION Pain Research Registry study builds on the concepts espoused in the Precision Medicine Initiative and addresses long-term goals established by the National Institutes of Health by assessing how precision medicine may prevent and treat chronic pain.