FDA Faulted for Spotty Oversight of Data Coming from Overseas

In a statement, Dr. Sidney Wolfe, director of the health arm of the consumer advocacy group Public Citizen and an outspoken critic of the FDA, said the HHS report "confirms some of the worst fears about the serious dangers of the escalating globalization of human experimentation."

"In addition to the increased dangers to human subjects in many countries because they have less adequate protections than in the United States, there are significant threats to the integrity of the data being generated from these experiments because of the decreased ability of FDA to monitor and inspect foreign sites," Wolfe wrote.

Dr. Steve Nissen, a cardiologist at the Cleveland Clinic, told MedPage Today and ABC News in an email that the increasing reliance on foreign trial data is "a significant problem."

"Patients enrolled overseas may differ substantially from U.S. patients. For example, some drugs (rosuvastatin, Crestor) achieve high blood levels in Asians. Other drugs have a different profile of adverse events in non-Caucasians," Nissen said.

He also pointed out that trials may be conducted in countries with high smoking rates and low use of lipid-lowering drugs, which "may make therapies look more efficacious than observed in well-treated non-smoking subjects."

Nissen added that language differences can make documentation such as hospital records harder to interpret.

But Harvard's Dr. Christopher Cannon, a TIMI trials investigator, said overseas data don't pose problems. "The trials we are involved with have equally high standards at all site in all countries," he said. "We do the same oversight of monitoring at sites in all countries."

No Matter How It's Sliced...

Other physicians also said they were less worried by the report's findings.

"The important thing is the quality of the trial, not where it was conducted," said Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center in New York City.

Perhaps the report's most astonishing finding was that 78 percent of the 299,701 participants in trials submitted with the applications approved in 2008 were from outside the U.S.; 54 percent of the 11,944 trial sites were foreign.

The region that appeared most popular for conducting overseas trials was Western Europe, accounting for nearly 60 percent of overseas sites and participants.

But, the HHS investigators found, Central and South America was the favorite location when sponsors sought large numbers of participants per site. The average number of participants per trial site there was about 130, compared with less than 40 in Western Europe.

The report also indicated that FDA inspectors never visited trial sites in seven Latin American countries that accounted for some 40,000 trial participants.

When the agency did conduct inspections, it was usually when the trial site was especially large or when the drug had not yet been approved in the U.S. for any purpose.

Overseas sites were inspected much less frequently than those in the U.S., the investigation disclosed. "Our regression analysis indicated that FDA was 16 times more likely to inspect a clinical investigator at a domestic site than a foreign site," according to the report.

FDA staff told the investigators that logistical challenges hamper their ability to inspect foreign trial sites.

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