Moving Clinical Trials Overseas Tests the System's Safety, Efficacy

Newswise — Major U.S. drug companies are increasingly performing clinical trials in developing countries, raising serious concerns about the efficacy, ethics and economics of drug development, according to a study in the current issue of the New England Journal of Medicine.

"There are powerful forces luring clinical trials overseas, including the lower cost of doing business and access to larger study populations," says Seth Glickman, M.D., the study's lead author and an assistant professor of emergency medicine at the University of North Carolina at Chapel Hill School of Medicine.

"We cannot afford to trade lower costs of drug development for drugs that may be less safe and less effective," Glickman says.

Since 2002, the number of Food and Drug Administration investigators based outside the United States grew 15 percent per year, while those in the U.S. dropped by more than 5 percent, the study found. Glickman and his co-authors reviewed government registries of Phase III clinical trials and studies of industry-sponsored trials in 2007, and 300 articles reporting clinical trial results appearing in the New England Journal of Medicine, the Journal of the American Medical Association and Lancet in 1995 and 2005.

According to the researchers, one-third of these trials from the 20 largest pharmaceutical companies in 2007 were being conducted outside the U.S., and a majority of all trial sites were abroad. They also found that from 1995 to 2005, the number of clinical trial sites overseas doubled, while the number in the U.S. and Western Europe decreased.

One obvious cause for this move is economic. The price per case for a clinical trial at a top-rated medical center in India is about $2,000; in the U.S., it would cost 10-times as much. In 2000, the average cost to develop one drug in the U.S. was $802 million, with most of the expense resulting from time costs. Countries with fewer regulations can move trials along faster.

But with lower costs comes less stringent scientific and ethical standards, and the U.S. regulatory system, chiefly the FDA, is already strained.

"This is outsourcing not only of jobs but of the way we test drugs to make sure they are safe and effective," says Charles Cairns, M.D., chairman of emergency medicine at UNC and a co-author of the study. "Across the globe there are different standards and no uniform approach to conducting clinical trials."

Ethical concerns include the lack of trial oversight and review of study protocols, as well as the monetary lure of participating in trials, especially in low-income countries. Also, many of the drugs tested in developed countries are for conditions that are not primary health problems there " allergies or overactive bladder instead of tuberculosis or malaria which disproportionately affect these countries.

Genetics and cultural and social factors also influence how drugs are metabolized. For instance, people of Asian decent have a genetic variance that decreases the efficacy of drugs like nitroglycerin. Many people in developing countries are also "drug naive," and have never taken medicine for depression or other chronic conditions. Their bodies would react differently to a drug than someone in a country like the United States who takes multiple medications and receives routine medical care.

"It is conceivable that use of the same drug in both populations would produce markedly different results," Glickman says.

The problems overseas are often rooted in the U.S. Higher labor costs, time-consuming bureaucracy and a lack of uniformity even in the U.S. regulatory system drives drug makers to look for places that are more conducive to running trials in a cost-effective manner, Cairns says.

The solution lies in a multi-faceted approach to increase cooperation with countries overseas while improving the domestic environment and increasing accountability on the part of industry, says Glickman.

"The U.S. Food and Drug Administration can be a leader globally in addressing these issues," says Cairns. "The FDA could be a nexus of insurers, providers, industry, patients " so that we could agree on minimal standards that can be transportable across countries.

"This could almost be considered a State Department issue. Energy and global warming are security issues; this is a medical security issue that needs to be actively discussed."

"Clearly, there is some benefit for everyone involved in clinical trials overseas," says Glickman. "But we need a robust research framework that will protect trial participants and ensure that clinical research is conducted to the highest scientific standards."