As many American companies in the last decade have sent tasks such as customer service and computer support to other countries, drug makers have followed suit by outsourcing clinical trials—the human studies that determine the safety and efficacy of medicines.
Now, an article about the globalization of clinical trials, published on Thursday in The New England Journal of Medicine has raised questions about the ethics and the science of increasingly conducting studies outside the US—when the studies were meant to gather evidence for new drugs to gain approval in this country.
The article, by several Duke University researchers, suggests an ethical quagmire when drugs intended for wealthy nations are tested on people in developing countries.
The authors suggest that human volunteers in foreign countries may be unduly influenced with the promise of financial compensation or free medical care to participate in clinical trials.
The report, Ethical and Scientific Implications of the Globalization of Clinical Research, also asks whether drug research conducted in developing countries is relevant to the treatment of American patients.
“We don’t want to imagine that lower-income countries are the clinical trial mill for higher-income countries,” Kevin A. Schulman, the lead author of the article, said in a phone interview last week. Dr Schulman is a professor of medicine at the Fuqua School of Business at Duke, in Durham, North Carolina.
But some critics say the authors used overly simplistic data mining to raise an alarm, without presenting hard evidence of widespread ethical or scientific problems.
“More places outside the United States are participating in research—is that a bad thing?” said Ezekiel J. Emanuel, the chairman of bioethics at the Clinical Center of the National Institutes of Health (NIH) in Bethesda, Maryland, after reading an abstract of the article sent to him by a reporter.
Dr Emanuel cited a clinical trial of the Merck and Co. Inc. drug Gardasil, a vaccine against the human papilloma virus, that was conducted in Costa Rica, where there is a high incidence of the disease. “This is the kind of case where it is a good thing.”
Whatever the interpretations, the use of offshore clinical trials is growing. In the last 10 years, the proportion of US-based researchers who direct clinical trials registered with the federal Food and Drug Administration (FDA) has declined significantly, while the percentage of FDA-registered researchers outside the US has significantly increased, according to a report in January by the Tufts Center for the Study of Drug Development in Boston.
In 1997, about 86% of FDA-registered principal investigators were based in the US, the Tufts study said. By 2007, only about 54% of about 26,000 FDA-regulated chief scientists who conducted clinical trials that year were based in the US.
Kenneth A. Getz, a senior research fellow at the Tufts center, said drug companies were looking abroad because it was often less expensive to conduct clinical trials outside the US.
Critics of the Duke article take issue with its methodology. The authors, for example, compare the locations of 300 clinical trials published in three leading medical journals in 1995 and 2005, concluding that the number of countries participating in studies more than doubled over that decade.
But critics question that comparison, because about 40% of the published clinical trials from 1995 did not indicate where the studies were conducted.
One of the authors, Seth W. Glickman, a senior scholar at the Fuqua School of Business at Duke, said he did not know how omitting those studies might have skewed the analysis. And although the article uses the country statistics to raise concerns about the increased globalization of clinical research, the Tufts study shows that the majority of FDA-regulated drug researchers are still in the US.
The Duke authors also write that drug research in developing countries—where certain populations may metabolize medications differently because of environmental factors or genetic mutations—might not be relevant for American patients. “There are issues with the interpretability of the findings,” Dr Glickman said.
Dr Emanuel of the NIH agreed that it was possible that some offshore drug research might not be applicable to American patients. But he faulted the report for seeming to treat all foreign countries alike.
Research conducted in some places outside the US—such as Canada and Sweden—might be perfectly relevant to American patients, he said.
“It’s not a sufficiently nuanced concern to give it credibility,” said Emanuel.
© 2009/THE NEW YORK TIMES