HHS Report Recommends Improvements to FDA's Regulation of Foreign Clinical Trials

The Office of the Inspector General for the Department of Health and Human Services (HHS) issued a report, Challenges to FDA’s Ability to Monitor and Inspect Foreign Clinical Trials, which evaluates the incidence of foreign clinical trials, the ability of the US Food and Drug Administration to oversee these trials, and recommendations to FDA on how to improve its oversight of foreign clinical trials.

The report said that 80% of approved marketing applications for drugs and biologics contained data from foreign clinical trials. More than half of clinical-trial subjects and sites were located outside the United States. Western Europe accounted for the most foreign clinical-trial subjects and sites. Central America and South America had the highest average number of subjects per site. The report also cited a study that showed that the 20 largest pharmaceutical companies were conducting one-third of their clinical trials exclusively at foreign sites.

FDA’s inspection of clinical investigators overall was relatively low and lower for foreign clinical trials compared with domestic clinical trials, according to the report. FDA inspected clinical investigators at only 1.2% of clinical-trial sites for applications in fiscal year 2008. FDA inspected 1.9% of domestic clinical-trial sites and 0.7% of foreign clinical-trial sites.

The report concluded that “challenges to conducting foreign inspections and data limitations inhibit FDA’s ability to monitor foreign clinical trials.” The report added that FDA may be unaware of some ongoing, early-phase clinical trials because sponsors are increasingly conducting early-phase clinical trials outside the US without investigational new drug (IND) applications. The problem is further compounded by logistical challenges and sponsor submission of clinical-trial data in a nonstandard format as well as the inability of FDA to account for all clinical-trial information because of missing or incomplete information on site locations and subject enrollment.

HHS made several recommendations for FDA to improve its oversight of foreign clinical-trials data. These include:

• FDA should require standardized electronic clinical-trial data and create an internal database to systemically cull clinical-trial information to more effectively select sites for inspection

• FDA should monitor trends in foreign clinical trials not conducted under INDS, and if necessary take steps to encourage sponsors to file INDs

• FDA should continue exploring ways to expand its oversight of foreign-clinical trials, which might include developing inspectional agreements with foreign regulatory bodies, inspecting clinical trials in more countries, and looking to new models of oversight such as a quality-risk management approach.

HHS said that FDA has agreed with its recommendations.