FDA faulted on foreign trials oversight

A new report from the Office of the Inspector General (OIG) at the US Department of Health and Human Services has found that the US Food and Drug Administration (FDA) needs to step up its oversight of foreign clinical trials conducted by drugmakers in support of their US marketing applications.

The issue is not marginal: around 80 per cent of approved US marketing applications for drugs and biologics are based in part on data from foreign clinical trials, and over half of clinical trial subjects and sites are located outside the US, according to the report. Nonetheless, the FDA inspects clinical investigators at less than 1 per cent of foreign sites, the OIG said.

Part of the problem stems from the fact that the FDA is often simply unaware of early-stage foreign trials, the report notes. In addition, drugmakers' submissions are often in a non-standard format and fail to provide study site locations, making it difficult for the FDA to properly evaluate the studies.

The OIG made three main recommendations for improvement, all of which it said the FDA agreed with. First, the FDA should require drug sponsors to submit trial data in a standardised electronic format and should create an internal database "to systematically cull clinical trial information and enable FDA to more effectively select sites for inspection and meet its review timelines."

Second, the FDA should monitor trends in foreign clinical trials not conducted under Investigational New Drug (IND) applications approved by the US agency to asses whether subjects are at additional risk and whether the data collected are accurate and reliable. If necessary, the agency should encourage sponsors to file INDs, the report recommends.

Third, the FDA should continue to explore ways to expand its oversight of foreign clinical trials, including continuing to develop inspectional agreements with foreign regulatory bodies, inspecting clinical trials in more countries, and looking to new models of oversight for foreign clinical trials, such as a quality risk-management approach.

Responding to the report, Pharmaceutical Research and Manufacturers of America (PhRMA) senior vice president Ken Johnson did not address the FDA's enforcement of regulations for foreign clinical trials, instead stressing that adequate regulations are on the books and also that companies can successfully self-regulate.

"It's important to remember that the Food and Drug Administration has jurisdiction over clinical trials conducted in foreign countries for drugs approved in the US or being studied for approval in the US," he said in a statement. "The same strict regulatory standards apply to foreign trials as trials conducted domestically [and] sponsors are typically in communication with the FDA throughout clinical trials no matter where they are conducted."

"Our member companies are committed to adhering to Good Clinical Practice guidelines around the world," Johnson added.

"In fact, PhRMA has conducted educational seminars and symposiums – at times in conjunction with the FDA – in other countries to educate potential clinical trial principal investigators about Good Clinical Practices, ethics oversight by outside review boards, and the need to maintain the highest standards for data quality."