The Major Role of Clinicians in the Discovery of Off-Label Drug Therapies

Objective: To determine, through a review of the medical literature and author contact, the role of clinicians in the discovery of off label use of Food and Drug Administration approved prescription drugs. Data Sources: The literature was accessed through MEDLINE (1999-December 2003). Additional sources accessed included the U.S. Patent Office and Micromedex, Thompson Scientific and Healthcare, Inc. Data Synthesis: 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 time period, a total of 144 new applications were identified in a computerized search of the literature for the 29 new drugs 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 via survey and telephone interview to determine whether they were in fact the originators of the new applications. If they were, examinations of article contents and author surveys were used to explore whether each new application was discovered via clinical practice that was independent of pharmaceutical company or university research (field discovery) or whether the discovery was made by or with the involvement of pharmaceutical firm or university researchers (central discovery). Conclusions: Post-NDA discoveries of new, off-label uses for new drugs were present in 22 of the 29 drugs in our sample. We found that 59% (85/144) of the drug therapy innovations in our sample were discovered by practicing clinicians via field discovery. 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.