Drug, patient, and physician characteristics associated with off-label prescribing in primary care

Arch Intern Med. 2012 May 28;172(10):781-8. doi: 10.1001/archinternmed.2012.340.


Background: Off-label prescribing may lead to adverse drug events. Little is known about its prevalence and determinants resulting from challenges in documenting treatment indication.

Methods: We used the Medical Office of the XXI Century electronic health record network in Quebec, Canada, where documentation of treatment indication is mandatory. One hundred thirteen primary care physicians wrote 253 347 electronic prescriptions for 50 823 patients from January 2005 through December 2009. Each drug indication was classified as on-label or off-label according to the Health Canada drug database. We identified off-label uses lacking strong scientific evidence. Alternating logistic regression was used to estimate the association between off-label use and drug, patient, and physician characteristics.

Results: The prevalence of off-label use was 11.0%; of the off-label prescriptions, 79.0% lacked strong scientific evidence. Off-label use was highest for central nervous system drugs (26.3%), including anticonvulsants (66.6%), antipsychotics (43.8%), and antidepressants (33.4%). Drugs with 3 or 4 approved indications were associated with less off-label use compared with drugs with 1 or 2 approved indications (6.7% vs 15.7%; adjusted odds ratio [AOR], 0.44; 95% CI, 0.41-0.48). Drugs approved after 1995 were prescribed off-label less often than were drugs approved before 1981 (8.0% vs 17.0%; AOR, 0.46; 95% CI, 0.42-0.50). Patients with a Charlson Comorbidity Index of 1 or higher had lower off-label use than did patients with an index of 0 (9.6% vs 11.7%; AOR, 0.94; 95% CI, 0.91-0.97). Physicians with evidence-based orientation were less likely to prescribe off-label (AOR, 0.93; 95% CI, 0.88-0.99), a 7% reduction per 5 points in the evidence section of the Evidence-Practicality-Conformity Scale.

Conclusions: Off-label prescribing is common and varies by drug, patient, and physician characteristics. Electronic prescribing should document treatment indication to monitor off-label use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Attitude of Health Personnel
  • Drug Prescriptions / statistics & numerical data*
  • Electronic Prescribing / statistics & numerical data
  • Female
  • Health Care Surveys
  • Humans
  • Male
  • Middle Aged
  • Off-Label Use / statistics & numerical data*
  • Physician-Patient Relations
  • Practice Patterns, Physicians' / trends*
  • Prevalence
  • Primary Health Care / standards
  • Primary Health Care / trends*
  • Quebec
  • Risk Assessment
  • Safety Management
  • Total Quality Management