"Without enforcement, it's been hard to persuade investigators to do what they need to do," explained Bowen. "I have seen companies venture into places like these and, almost invariably, the quality of the data is not what they hoped to see. But recruitment is good, and that's what seduces them. It seems to our board that the recruiting in Eastern Europe is rather aggressive. The FDA simply does not have the resources to monitor and audit all these sites," she said. "Neither," she adds, "does the Office for Human Research Protection."

An analysis of FDA investigative site inspection results supports WIRB's experience. Historically, the incidence of noncompliance and fraud is higher among principal investigators based outside the United States.

Informed consent, drug accountability, and adverse event reporting are among the areas where noncompliance is substantially higher for principal investigators not based in the United States. In addition, there is high variability in the incidence of investigator noncompliance and fraud between countries within a given ex-U.S. region.

The Rate of Increase for FDA Regulated Investigators Around the Globe

Globally active sponsors and CROs must understand and be attentive to the details of each country in order to deliver development performance and economic advantages. "Every region has individual countries with unique characteristics," said Merck's Madai. "There are those places where the political situation may endanger clinical research work; the quality of data provided by a country's investigators varies between country; and regulatory and import authorities are not the same in each country."

Kenneth A. Getz MS, MBA, is a Senior Research Fellow at the Tufts CSDD and Chairman of CISCRP, both in Boston, MA, email: kenneth.getz@tufts.edu