A Cluster-Randomized Clinical Trial to Decrease Prescription Opioid Misuse: Improving the Safety of Opioid Therapy (ISOT)

Benjamin J. Morasco, Melissa H. Adams, Elizabeth R. Hooker, Patricia E. Maloy, Erin E. Krebs, Travis I. Lovejoy, Somnath Saha, Steven K. Dobscha

Research output: Contribution to journalArticlepeer-review


Background: Interventions to reduce harms related to prescription opioids are needed in primary care settings. Objective: To determine whether a multicomponent intervention, Improving the safety of opioid therapy (ISOT), is efficacious in reducing prescription opioid harms. Design: Clinician-level, cluster randomized clinical trial. (ClinicalTrials.gov: NCT02791399) Setting: Eight primary care clinics at 1 Veterans Affairs health care system. Participants: Thirty-five primary care clinicians and 286 patients who were prescribed long-term opioid therapy (LTOT). Intervention: All clinicians participated in a 2-hour educational session on patient-centered care surrounding opioid adherence monitoring and were randomly assigned to education only or ISOT. ISOT is a multicomponent intervention that included a one-time consultation by an external clinician to the patient with monitoring and feedback to clinicians over 12 months. Main Measures: The primary outcomes were changes in risk for prescription opioid misuse (Current Opioid Misuse Measure) and urine drug test results. Secondary outcomes were quality of the clinician-patient relationship, other prescription opioid safety outcomes, changes in clinicians’ opioid prescribing characteristics, and a non-inferiority analysis of changes in pain intensity and functioning. Key Results: ISOT did not decrease risk for prescription opioid misuse (difference between groups = −1.12, p = 0.097), likelihood of an aberrant urine drug test result (difference between groups = −0.04, p=0.401), or measures of the clinician-patient relationship. Participants allocated to ISOT were more likely to discontinue prescription opioids (20.0% versus 8.1%, p = 0.007). ISOT did not worsen participant-reported scores of pain intensity or function. Conclusions: ISOT did not impact risk for prescription opioid misuse but did lead to increased likelihood of prescription opioid discontinuation. More intensive interventions may be needed to impact treatment outcomes.

Original languageEnglish (US)
Pages (from-to)3805-3813
Number of pages9
JournalJournal of general internal medicine
Issue number15
StatePublished - Nov 2022

Bibliographical note

Funding Information:
Research reported in this manuscript was supported by grant 1I01HX001583 from VA Health Services Research & Development. The work was also supported by resources from the VA Health Services Research and Development–funded Center to Improve Veteran Involvement in Care at the VA Portland Health Care System (CIN 13-404). No author reports having any potential conflict of interest with this study. The content of this manuscript is solely the responsibility of the authors and does not represent the official views of the Department of Veterans Affairs.

Publisher Copyright:
© 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.


  • adverse effects
  • chronic pain
  • long-term opioid therapy
  • treatment guidelines

PubMed: MeSH publication types

  • Randomized Controlled Trial
  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.


Dive into the research topics of 'A Cluster-Randomized Clinical Trial to Decrease Prescription Opioid Misuse: Improving the Safety of Opioid Therapy (ISOT)'. Together they form a unique fingerprint.

Cite this