The Agency for Healthcare Research and Quality (AHRQ), through its Evidencebased Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist publicand private-sector organizations in their efforts to improve the quality of health care in the United States. The reports and assessments provide organizations with comprehensive, science-based information on common, costly medical conditions and new health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments. AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality. The full report and this summary are available at www.effectivehealthcare.ahrq. gov/reports/final.cfm. d. In patients with chronic pain, what is the comparative effectiveness of opioids plus nonopioid interventions (pharmacological or nonpharmacological) versus opioids or nonopioid interventions alone on outcomes related to pain, function, quality of life, and doses of opioids used? Key Question 2. Harms and Adverse Events a. In patients with chronic pain, what are the risks of opioids versus placebo or no opioid on: (1) opioid abuse, addiction, and related outcomes; (2) overdose; and (3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular 3 events, cognitive harms, and psychological harms (e.g., depression)? b. How do harms vary depending on: (1) the specific type or cause of pain (e.g., neuropathic, musculoskeletal [including back pain], fibromyalgia, sickle cell disease, inflammatory pain, headache disorders); (2) patient demographics; (3) patient comorbidities (including past or current substance use disorder or at high risk for addiction); (4) the dose of opioids used? Key Question 3. Dosing Strategies