OIG Issues Recommendations to FDA to Improve its Oversight of Foreign Clinical Trial Data

By Carrie S. Martin –

The Office of Inspector General (“OIG”) recently issued a report detailing the inclusion of foreign clinical trial data in New Drug Applications (“NDAs”) and Biologics License Applications (“BLAs”) and FDA’s oversight of foreign clinical trial sites.  The OIG examined all NDAs and BLAs, and related documents, submitted in Fiscal Year (“FY”) 2008 with two questions in mind: (1) how much foreign data did sponsors submit in their marketing applications; and (2) to what extent did FDA monitor and inspect these foreign clinical trials.  The answers: (1) a lot; and (2) not enough.

OIG found that 80% of approved NDAs and BLAs in FY 2008 contained data from foreign clinical trials.  Although most subjects and sites were located in Western Europe, Central and South America accounted for the highest average number of subjects per site.  Usually, only one clinical investigator oversees a clinical trial site.  OIG also determined that FDA inspected only 0.7% of foreign clinical trial sites in FY 2008.  (That being said, FDA inspected only 1.9% of U.S. sites.)  Finally, the report noted that data limitations inhibited FDA’s ability to inspect foreign sites, including, for example, the failure of sponsors to submit complete information on site locations and subject enrollment.  Some of these data omissions may be understandable:  federal law does not require an Investigational New Drug (“IND”) application for clinical trials conducted exclusively outside the U.S.  INDs serve as FDA’s primary method of collecting information on clinical trials.

OIG acknowledged the perceived benefits of foreign trials – lower clinical trial costs, larger populations from which to collect patients, and the desire to obtain foreign marketing approvals.  The downside, according to critics, is the lack of patient protection due to inadequate monitoring and the ability to “generalize” foreign data to the U.S. population.

Based on its research, OIG made three recommendations to FDA: (1) require standardized electronic clinical trial data and create an internal database from which FDA can select sites for inspection; (2) monitor trends in foreign clinical trials not conducted under INDs and take steps as necessary to encourage sponsors to file INDs; and (3) explore additional ways to expand the Agency’s oversight of foreign clinical trials, including agreements with foreign regulatory bodies and inspections of clinical trial sites in countries not previously inspected. 

FDA generally agreed with OIG’s recommendations and is seeking to address each recommendation.  For FDA’s full response, see Appendix E of the report.  OIG predicts that the reliance on foreign data will grow in coming years; this will undoubtedly increase the pressure on FDA to adopt new ways to ensure patient protection and the integrity of foreign data.