High dose oral colchicine has been utilized for the treatment of acute gouty arthritis for several centuries. This use predates the rigorous FDA approval process in the recent decades, and so the manufacture, prescription, and use of colchicine were not rigorously evaluated in controlled settings. Toxicity studies have provided evidence of significant interactions between colchicine and other commonly used medications such as statins and macrolides. In 2009 the FDA provided approval and market exclusivity for a single agent colchicine preparation (Colcrys(R)) following studies that provided data to suggest that a) lower dose of Colcrys(R) may be as efficacious as the higher dose colchicine and that b) the adverse effects for lower dose colchicine may be much lower than that of the traditional high dose regiment. This has triggered a major controversy and questions about the impact of the FDA Unapproved Drug Initiative. We propose to study the impact of the Colcrys(R) approval, the related media publicity and the Phase 2 and 3 study data in real world gout flare treatment. The first specific aim will be to use Stanford Medical Center electronic medical records to perform a comparison of colchicine utilization patterns before and after approval of Colcrys(R). The second specific aim will be to perform a prospective observational study of patients with gout over a 3-year period in order to identify the prevalence and risk factors for unsafe/unapproved colchicine use. This cohort study will be supplemented by a qualitative study that will identify the intangible factors such as health beliefs, health literacy and self-efficacy that are associated with unsafe/unapproved colchicine use. We hypothesize that we will be able to demonstrate large-scale improvements safety of colchicine use in clinical settings thereby providing an evidence base for the success of FDA Unapproved Drug Initiative and provide data for a root-cause analysis for prevention of continuing unsafe use of this drug.

Public Health Relevance

Colchicine, a common, potentially toxic treatment for gouty arthritis that affects over 8 million Americans has been brought under the purview of the FDA Unapproved Drug Initiative in 2009 but it is not known if this has resulted in safer utilization in clinical settings. Our study will assess the impact of this Initiative on colchicine use and will provide data that supports its continuation and expansion.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01FD004257-02
Application #
8337616
Study Section
Special Emphasis Panel (ZFD1-SRC (99))
Project Start
2011-09-16
Project End
2014-09-15
Budget Start
2012-09-16
Budget End
2013-09-15
Support Year
2
Fiscal Year
2012
Total Cost
Indirect Cost
Name
Stanford University
Department
None
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305