The Rise of Unregulated Drug Trials in South America
When her son’s diarrhea wouldn’t stop, Diana Canessa, cash-strapped and panicky, scraped together some change, grabbed her last diaper and headed for the emergency room at Lima’s public hospital for children. It was there, she says, that a nurse offered free oral rehydration therapy for her son, Fabrizio, and free meals and diapers for her.
Canessa was given a form to fill out. “I didn’t understand some of the words,” she said. “But they told me, Apurate, mamita. Apurate.” Hurry, hurry. After the two-day treatment, Fabrizio’s diarrhea subsided. Canessa got diapers and rash cream and a taxi home. But when the diarrhea returned a few days later, the people at the hospital were less helpful. “They gave me a ball and some more cream and sent me home,” she said. “They said the problem was his diet.” Then one day she saw a man on the news talking about how babies at the children’s hospital had been given an experimental oral rehydration therapy containing a genetically modified rice solution made in the United States. Soon she was telling her story to reporters. She fears Fabrizio’s allergies and chronic health problems are related to the treatment he received. “Nobody said anything about it being an experiment,” she told me. “I would never have agreed if I had known. I worry all the time.”
It could have been worse. In 2008, in the Argentine province of Santiago del Estero, seven babies died while taking part in trials for an experimental vaccine made by GlaxoSmithKline to prevent pneumonia and related diseases. Their mothers claimed they also didn’t know.
Or consider what happened in the case of Ketek, an antibiotic drug used for respiratory tract infections. In 2000 Sanofi-Aventis conducted a series of clinical trials in the United States and abroad. One Alabama doctor was paid $400 a head to recruit patients and caught the eye of FDA reviewers for signing up subjects in droves. She ultimately went to jail for falsifying data in 91 percent of her cases; another doctor presiding over trials was arrested on cocaine and gun charges. Despite warnings from its reviewers, the FDA allowed Sanofi-Aventis to submit foreign trial data in place of that compromised domestic research—Ketek got the green light for sale in 2004. It wasn’t until 2007, after a dozen deaths from liver failure had been reported, that the FDA recommended restricting its use—a day before Congress was to investigate.
Foreign clinical trials for US-bound drugs have been commonplace for decades, and ethical breaches are a frequent side effect. Last year, a professor at Wellesley College unearthed evidence of a particularly egregious case from the 1940s in which scientists working for the Public Health Service deliberately infected Guatemalan prisoners, mental patients and soldiers with syphilis and other sexually transmitted diseases in order to study the effects of penicillin. President Obama apologized to Guatemala’s government and called for an investigation into the incident as well as current standards of practice. When the Presidential Commission for the Study of Bioethical Issues submitted its report in September, commission chair Amy Gutmann said, “We must look to and learn from the past so that we can assure the public that scientific and medical research today is conducted in an ethical manner.”
But is it? A generation ago, most human testing took place in American academic institutions. Now it’s a global game dominated by corporations, called contract research organizations (CROs), that help Big Pharma bring new molecules from the lab to your medicine cabinet. More and more drug companies are turning to CROs for assistance with trial design and recruitment, regulatory compliance, marketing and branding—last year the CRO market was worth $20 billion, an estimated 100 percent jump from a decade ago. And CROs, in turn, are increasingly running trials in the developing world because doing so is cheaper and faster: regulations aren’t as onerous, patient recruitment is easier and informed consent is less clearly defined.
The Food and Drug Administration is clearly unable to keep up with the astounding surge of outsourcing in recent years. According to the FDA, the number of trials in developing countries has grown 8 percent a year since 1997. A 2010 report by the inspector general of the Department of Health and Human Services (HHS) notes that 40 to 65 percent of clinical trials on FDA-regulated products in 2008 took place overseas. Of nearly 6,500 foreign trial sites that year, the FDA inspected only forty-five—less than 1 percent.
What’s worse, the dramatic rise of offshore clinical trials has coincided with a loosening of standards guiding their practice. At a time when federal regulators should be scrambling to improve oversight, they are instead making it easier for the pharmaceutical industry to speed drugs to market.
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Although recent coverage of American drug studies in the developing world has tended to focus on India and Africa, trials south of the US border have quietly spiked. The HHS report found that Central and South America had the highest number of subjects per site and accounted for 26 percent of all subjects enrolled in foreign trials.
Peru, a nation of 30 million where few people have health insurance and one in three lives in poverty, has the highest number of volunteer patients in South America and ranks among the world’s leaders in total number of clinical trials. In 2008 more than 13,000 Peruvians took part in trials testing drugs intended for the United States. The FDA did not send a single inspector.
The country is a “paradise of human experimentation,” says Herberth Cuba, a Peruvian gynecologist who runs a watchdog group called the Peruvian Medical Association, or AMP. In a cafe in Lima’s posh Miraflores district, he talked about “medical colonialism,” a system rife with financial conflicts of interest where powerful Peruvian doctors who run big public hospitals find it all too easy to benefit from recruiting patients for trials. He said Peru has many competent and honest doctors but that poverty leads to exploitation. It was Cuba whom Diana Canessa saw on television talking about the rice experiment, and it was AMP that sued on her behalf, only to find the case stalled. “A judge asked to see the clinical trial data, but it had been destroyed,” he said. “That’s how it works in Peru. If an investigator doesn’t like what the data says, he burns it.”
The agency that monitors and approves clinical trials in Peru, part of the country’s National Health Institute, is known by its Spanish initials, OGITT. A former OGITT investigator, speaking to The Nation on condition of anonymity, provided several confidential government documents to support the claim that the agency is rife with corruption, a place where anyone getting in the way of multimillion-dollar trials faces heavy pressure.
In a 2007 memo to OGITT’s top official, for example, the agency’s head of investigation reported that an HIV/AIDS trial had been flagged as “controversial” and that a technical committee had been put together to review it. But just twenty-four hours later, the same official told his supervisor that the trial did not meet the legal requirements to justify the committee’s review, and asked that it be approved. In another document from 2007, OGITT medical reviewers reported that a Peruvian researcher at the country’s cancer hospital (known as INEN) failed to report adverse side effects of a trial to the government, as required by law. Other papers show that superiors in OGITT’s office of inspection knew that trials slated for inspection lacked government authorization. And in at least one case, a disingenuous informed-consent document that failed to inform a patient with aggressive non-Hodgkin’s lymphoma about participation in an experimental treatment was signed with a fingerprint, presumably by an illiterate.
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After the Guatemala syphilis scandal broke last fall, the heads of the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention wrote that no such studies could take place these days because US-funded research is now subject to approval by institutional review boards (IRBs). These voluntary ethical oversight committees are made up of healthcare professionals and community members who have legal authority to stop clinical trials deemed unethical.
But for all the faith we’re asked to put in IRBs, there is evidence of big problems. Because the FDA also requires drug companies to have IRB approval for their private research, for-profit companies have popped up to sell their ethical review services to the highest bidder. In 2009 the Government Accountability Office netted a Colorado-based IRB that had approved a fake research study invented by undercover investigators. “The IRB system is vulnerable to unethical manipulation,” a GAO official told a Congressional committee.
If our IRB system is so messed up, what about those in South America and other parts of the developing world? How can they hope to hold their ground against Big Pharma?