The major role of clinicians in the discovery of off-label drug therapies

Pharmacotherapy. 2006 Mar;26(3):323-32. doi: 10.1592/phco.26.3.323.


Objective: To determine the role of clinicians in the discovery of off-label use of prescription drugs approved by the United States Food and Drug Administration (FDA). Data Sources. Micromedex Healthcare Series was used to identify new uses of new molecular entities approved by the FDA in 1998, literature from January 1999-December 2003 was accessed through MEDLINE, and relevant patents were identified through the U.S. Patent and Trademark Office.

Data synthesis and main finding: A survey of new therapeutic uses for new molecular entity drugs approved in 1998 was conducted for the subsequent 5 years of commercial availability. During that period, 143 new applications were identified in a computerized search of the literature for the 29 new drugs considered and approved in 1998. Literature and patent searches were conducted to identify the first report of each new application. Authors of the seminal articles were contacted through an electronic survey to determine whether they were in fact the originators of the new applications. If they were, examination of article content and author surveys were used to explore if each new application was discovered through clinical practice that was independent of pharmaceutical company or university research (field discovery) or if the discovery was made by or with the involvement of pharmaceutical company or university researchers (central discovery). Eighty-two (57%) of the 143 drug therapy innovations in our sample were discovered by practicing clinicians through field discovery.

Conclusion: To our knowledge, the major role of clinicians in the discovery of new, off-label drug therapies has not been previously documented or explored. We propose that this finding has important regulatory and health policy implications.

MeSH terms

  • Botulinum Toxins, Type A / therapeutic use
  • Cosmetics
  • Dermatologic Agents / therapeutic use
  • Drug Approval
  • Drug Industry
  • Drug Labeling
  • Humans
  • Pharmaceutical Preparations
  • Physicians*
  • Product Surveillance, Postmarketing*
  • Propofol / therapeutic use
  • United States
  • United States Food and Drug Administration


  • Cosmetics
  • Dermatologic Agents
  • Pharmaceutical Preparations
  • Botulinum Toxins, Type A
  • Propofol