Effect of Mobile Device-Assisted N-of-1 Trial Participation on Analgesic Prescribing for Chronic Pain: Randomized Controlled Trial
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Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for chronic musculoskeletal pain, despite limited evidence of effectiveness and well-documented adverse effects. We assessed the effects of participating in a structured, personalized self-experiment (“N-of-1 trial”) on analgesic prescribing in patients with chronic musculoskeletal pain.
We randomized 215 patients with chronic pain to participate in an N-of-1 trial facilitated by a mobile health app or to receive usual care. Medical records of participating patients were reviewed at enrollment and 6 months later to assess analgesic prescribing. We established thresholds of ≥ 50, ≥ 20, and > 0 morphine milligram equivalents (MMEs) per day to capture patients taking relatively high doses only, patients taking low-moderate as well as relatively high doses, and patients taking any dose of opioids, respectively.
There was no significant difference between the N-of-1 and control groups in the percentage of patients prescribed any opioids (relative odds ratio (ROR) = 1.05; 95% confidence interval [CI] = 0.61 to 1.80, p = 0.87). There was a clinically substantial but statistically not significant reduction of the percentage of patients receiving ≥ 20 MME (ROR = 0.58; 95% CI = 0.33 to 1.04, p = 0.07) and also in the percentage receiving ≥ 50 MME (ROR = 0.50; 95% CI = 0.19 to 1.34, p = 0.17). There was a significant reduction in the proportion of patients in the N-of-1 group prescribed NSAIDs compared with control (relative odds ratio = 0.53; 95% CI = 0.29 to 0.96, p = 0.04), with no concomitant increase in average pain intensity. There was no significant change in use of adjunctive medications (acetaminophen, gabapentenoids, or topicals).
These exploratory results suggest that participation in N-of-1 trials may reduce long-term use of NSAIDs; there is also a weak signal for an effect on use of opioids. Additional research is needed to confirm these results and elucidate possible mechanisms.
ClinicalTrials.gov Identifier: NCT02116621.
Key WordsN-of-1 trials chronic pain non-steroidal anti-inflammatory agent opioid analgesic
The authors thank the Scientific Advisory Board members for their valuable suggestions and recommendations on a variety of scientific issues, the study protocol, patient recruitment, retention, and adherence; Colin Barr, Sarah Benedetti, Navjot Dhammi, and Peach Dounias for their dedication and assistance with conducting patient visits, interviewing participants, and data collection activities; participating clinicians and medical staff at the University of California, Davis Primary Care Network, and Veterans Affairs Northern California Health Care System at Mather and McClellan Medical Centers for their efforts in patient recruitment and assisting patients completing N-of-1 trials; and study participants whose cooperation, commitment, and enthusiasm were critical to the study’s success.
The contents of this article are solely the responsibility of the authors and do not represent the views of the United States Government, United States Army, or Department of Veterans Affairs.
This research was supported by the National Institute of Nursing Research (1RO1NR013938) and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), through grant UL1 TR000002. Additional support through resources and the use of facilities was provided by Veterans Affairs, Northern California Health Care System (VANCHCS) at Mather and McClellan Medical Centers.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they do not have a conflict of interest.
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