Status of N-of-1 Trials in Chronic Pain Management: A Narrative Review.

N-of-1 trials are randomized controlled clinical trials conducted exclusively on a single patient. The ultimate aim of N-of-1 trials is to optimize a strategy in a particular individual. Chronic pain is a common but refractory clinical problem. Its diverse etiologies and broad variations among patients often lead to the requirement of individualizing medicine. Thus, chronic pain represents a classical condition for N-of-1 clinical trials. Studies have indicated that N-of-1 benefits patients with chronic pain, multiple comorbidities, and uncertain variations during therapies; however, this approach it is not yet adopted as the first choice in pain clinics. To dissect the current status of N-of-1 in chronic pain management, as well as the limitations for its implementation, we herein studied all N-of-1 studies related to chronic pain by searching three major databases (PubMed, ClinicalTrial.gov, Cochrane Library) for publications between 1985 and 2020. Of 35 eligibility papers, 19 were selected for analysis. Results confirmed that N-of-1 trials have solved the refractory cases including osteoarthritis, chronic musculoskeletal pain, and neuropathic pain; however, none of the trials dealt with cancer pain. Longer time and more efforts are needed from investigators when carrying out N-of-1 trials, which inevitably result in implementation difficulties. Of note, all recruited trials were conducted in developed countries. As mobile devices have been introduced and protocols improve, renewed interest in the implementation of N-of-1 trials will occur. Collectively, a previously underestimated conflict between "precision medicine" and "poor implementation" has put N-of-1 in a challenging position for chronic pain management.