Trial and Ire

June 1, 2009

Over the past five years, top-tier U.S.-based pharmaceutical companies have moved their clinical trials overseas at an accelerated rate, raising questions about ethics, quality control, and even the scientific value of their findings.

In a study published in the New England Journal of Medicine, researchers at the Duke Clinical Research Institute found that the trials are increasingly being conducted in developing nations in Eastern Europe and Asia, where participants are often poorer and less educated than their U.S. counterparts.

"The FDA is supposed to provide oversight for such trials, but it simply wasn't designed to handle this kind of situation," says Kevin Schulman, senior author of the report. Schulman says the number of Food and Drug Administration investigators based outside the U.S. has grown by 15 percent every year since 2002, while the number of U.S.-based investigators has fallen just over 5 percent during the same period.

Schulman and a research team led by Seth Glickman M.B.A. '06, a physician and a senior scholar at Fuqua, used the clinicaltrials.gov registry to examine recruitment patterns in industry-sponsored Phase III trials in 2007. Phase III trials are typically the largest and most meaningful trials, often involving thousands of patients. They found that, overall, more than half of drug-trial study sites are abroad.

The researchers also reviewed 300 articles reporting clinical-trial results appearing in the New England Journal of Medicine, the Journal of the American Medical Association, and the Lancet in 1995 and 2005. Over that decade, the number of clinical-trial sites abroad doubled, while the number in the U.S. and Western Europe declined.

The authors say some of the clinical trials abroad are raising concerns about whether or not the health-care needs of those studied are being met. "It's pretty clear that companies are testing drugs in countries where they will not be marketed or sold," says Glickman. "This is a major ethical concern."

The researchers found plenty of examples where companies were testing drugs for conditions such as allergic rhinitis, fibromyalgia, or overactive bladders in areas where they do not commonly appear, rather than treatments for diseases like malaria or tuberculosis that might be more prevalent. Glickman says that the environment and genetic factors may also play a role in trial outcomes, and may limit their applicability to patients who do not share those surroundings or characteristics.

"Generally, such trials increase local prosperity, education, and access to better health care," Glickman says. "In order for that to properly continue, however, we need a robust research framework that will protect trial participants and ensure that sponsors adhere to the highest ethical standards."