Human guinea pigs pay for lax FDA rules

Oscar Cabanerio has been waiting in an experimental drug-testing center in Miami since 7:30 a.m. The 41-year-old undocumented immigrant says he's desperate for cash to send to his family in Venezuela.

More than 70 people have crowded into reception rooms furnished with rows of attached blue plastic seats. Cabanerio is one of many regulars who gather at SFBC International's test center, which, with 675 beds, is the largest for-profit drug-trial site in North America.

Across the U.S., 3.7 million people have enrolled in drug tests sponsored by the world's largest pharmaceutical companies. The companies have outsourced 75 percent of experimental drug trials to centers such as SFBC, a leader in a $14 billion industry.

At the same time, the U.S. Food and Drug Administration has farmed out much of the responsibility for overseeing safety in these tests to private companies known as institutional review boards. These boards are also financed by pharmaceutical companies.

So, the drug industry is paying the people who do the tests — and most of the people who regulate those tests. And that combination can sometimes be deadly.

"The fundamental problem is a system in which investor-owned businesses have control over the evaluation of their own products," says Marcia Angell, editor in chief of the New England Journal of Medicine from 1999 to 2000. "Oversight of clinical trials is too important to leave in the hands of drug companies and their agents."

Most of the people lining up at SFBC to rent their bodies to medical researchers are poor immigrants from Latin America, drawn to this five-story test center in a converted Holiday Inn motel.

Inside, the brown paint and linoleum are gouged and scuffed. A bathroom with chipped white tiles reeks of urine; its floor is covered with muddy footprints and used paper towels. The volunteers, who are supposed to be healthy, wait for the chance to get paid for ingesting chemicals that may make them sick.

They are testing the compounds the world's largest pharmaceutical companies hope to develop into best-selling medicines.

Cabanerio, who has a mechanical drafting degree from a technical school, says he left Venezuela because he lost his job as a union administrator. For him, the visit to SFBC is a last resort. "I'm in a bind," Cabanerio says in Spanish. "I need the money."

Few doctors dispute that testing drugs on people is necessary. No amount of experimentation on laboratory rats will reliably show how a chemical will affect people. Helped by human testing, drug makers have developed antibiotics capable of curing life-threatening infections as well as revolutionary treatments for diseases like cancer and AIDS.

These medical success stories mask a clinical-drug-trial industry that is poorly regulated and riddled with conflicts of interest. Every year, trial participants are injured or killed.

Rules requiring subjects to avoid alcohol and narcotics and to take part in only one study at a time are sometimes ignored by participants, putting them at risk and tainting the test data.

The consent forms that people in tests sign — some of which say participants may die during the trial — are written in complicated and obscure language. Many drug-test participants interviewed said they barely read them.

Ken Goodman, director of the Bioethics Program at the University of Miami, says pharmaceutical companies are shirking their responsibility to safely develop medicines by using poor, desperate people to test experimental drugs.

"The setting is jarring," says Goodman, after spending 90 minutes in the waiting rooms at SFBC's Miami center, which is also the company's headquarters. "It's an eye-opener. Every one of these people should probably raise a red flag. If these human-subject recruitment mills are the norm around the country, then our system is in deep trouble."

Pharmaceutical companies distance themselves from the experiments on humans by outsourcing most of their trials to private test centers across the U.S. and around the world, says Daniel Federman, a doctor who is a senior dean of Harvard Medical School in Boston.

The FDA, the principal federal agency charged with policing the safety of human drug testing, has farmed out much of that responsibility to a network of private companies and groups called institutional review boards, or IRBs.

The review boards that oversee drug-company trials operate in such secrecy that the names of their members often aren't disclosed to the public. These review boards are paid by Big Pharma — just like the testing centers they're supposed to be regulating.

'Fundamental problem'

The drug-testing companies and the private oversight firms have more incentive to satisfy pharmaceutical companies wanting speedy results than they have to ensure the safety of participants or integrity of research data, says Angell, of the New England Journal of Medicine.

"The fundamental problem is a system in which investor-owned businesses have control over the evaluation of their own products," she says. "Oversight of clinical trials is too important to leave in the hands of drug companies and their agents."

The chief executives of drug companies should be held accountable for any lack of ethics in these tests, says Harvard's Federman, who chaired a national committee on clinical trial safety in 2003.

"It's not possible to insist on ethical standards unless the company providing the money does so," Federman says.

CEOs of 15 pharmaceutical companies that outsource drug testing to firms including SFBC — among them, Pfizer, the world's largest drugmaker; Merck & Co.; and Johnson & Johnson — declined to comment for this story.

SFBC Chief Executive Arnold Hantman says his center diligently meets all regulations.

"We take very seriously our responsibilities to regulatory authorities, trial participants, clients, employees and shareholders," Hantman says. "We are committed to conducting research that fully complies with industry and regulatory standards."

Outsourcing oversight

The pressure that pharmaceutical companies face to develop new drugs has intensified in the past 15 years.

Faced with the expiration of patents on best-selling drugs, such as AstraZeneca's Prilosec, which has helped tens of millions of people with heartburn and ulcers, Big Pharma has been in a frenzied race to find new sources of profit.

When the patent for a company's blockbuster drug expires, a lucrative monopoly vanishes. Such drugs typically lose 85 percent of their market share within a year of patent expiration, according to CenterWatch, a Boston-based compiler of clinical trial data.

The oldest and largest review company is Western IRB, founded in 1977 by Angela Bowen, an endocrinologist. WIRB, an Olympia-based for-profit company, is responsible for protecting people in 17,000 clinical trials in the U.S.

The company oversaw tests in California and Georgia in the 1990s for which doctors were criminally charged and jailed for lying to the FDA and endangering the lives of trial participants. No action was taken against WIRB. Bowen says she didn't see human safety issues in those trials.

WIRB aims to visit test sites it monitors once every three years, Bowen says.

The FDA's own enforcement records portray a system of regulation so porous that it has allowed rogue clinicians — some of whom have phony credentials — to continue conducting human drug tests for years, sometimes for decades.

The Fabre Research Clinic in Houston, for example, conducted experimental drug tests for two decades even as FDA inspectors documented the clinic had used unlicensed employees and endangered people repeatedly since 1980. In 2002, the FDA linked the clinic's wrongdoing to the death of a test participant.

Review boards can have blatant conflicts of interest. The one policing the Fabre clinic was founded by Louis Fabre, the same doctor who ran the clinic. Miami-based Southern IRB has overseen testing at SFBC and is owned by Alison Shamblen, wife of E. Cooper Shamblen, SFBC's vice president of clinical operations. Both Shamblen declined to comment.

SFBC's 2005 shareholder proxy, filed with the U.S. Securities and Exchange Commission, lists Lisa Krinsky as its chairwoman and a director of medical trials and refers to her 26 times as a doctor. Krinsky, 42, has a degree from Sparta Medical College in St. Lucia in the Caribbean; she is not licensed to practice medicine.

Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania in Philadelphia, says handing oversight of human drug experiments to private, for-profit companies is a mistake.

"This whole world gives me hives, this privatized review process," Caplan, 55, says. "I've never seen an IRB advertise by saying, 'Hire us. We're the most zealous enforcer of regulations you could have.' People say, 'We'll turn it around faster. We're efficient. We know how to get you to your deadlines.' "

The Pharmaceutical Research and Manufacturers of America, a trade association and lobbying group in Washington, D.C., says human drug tests in the U.S. are safe and well monitored.

"The vast majority of clinical trials conducted in the United States meet high ethical standards," PhRMA, as the group is known, said in a written response to questions. "The U.S. regulatory system is the world's gold standard, and the Food and Drug Administration has the best product safety record."

Joanne Rhoads, the physician who directs the FDA's Division of Scientific Investigations, says that view isn't realistic.

The agency doesn't have enough staff to aggressively monitor trials, she says, adding that FDA regulations are a bare minimum and much more oversight is needed. "You cannot rely on the inspection process to get quality into the system," Rhoads says. "I know many people find this not OK, but that's just the truth."

Michael Hensley, a pediatrician who was an FDA investigator from 1977 to 1982, says the agency has become less active in clinical trial oversight in recent years. He said families of those who died or were injured in trials have to file lawsuits if they want some accountability for mistakes.

"The FDA's backbone has been Jell-O," says Hensley, who's now president of Chapel Hill, N.C.-based Hensley & Pilc, which advises pharmaceutical companies on FDA compliance. "The folks at the FDA stopped enforcing the rules several years ago."

Private test centers

In 1991, 80 percent of industry-sponsored drug trials were conducted by medical faculty at universities, with protection for participants provided by the school's own oversight boards, according to the New England Journal of Medicine.

Now, more than 75 percent of all clinical trials paid for by pharmaceutical companies are done in private test centers or doctors' offices, according to CenterWatch.

Some test centers, FDA records show, have used poorly trained and unlicensed clinicians to give participants experimental drugs. The centers — there are about 15,000 in the U.S. — sometimes have incomplete or illegible records. In California and Texas, clinicians have used themselves, staff or family members as drug-trial participants.

"Unfortunately, I don't think it's been recognized how important it is that people who actually conduct the trial be trained," Rhoads says. "We oftentimes see people with no qualifications whatsoever, but they'll go to a one-day training course and they call themselves a certified study coordinator."

These people often run 90 percent of the study with little involvement by physicians, she says.

Participants in Miami clinical trials talk openly about how they violate SFBC rules intended to protect the integrity of research findings. SFBC bans people from taking part in two clinical trials at the same time.

Steve Simon, a research biostatistician at Children's Mercy Hospital in Kansas City, Mo., says that when participants are in more than one clinical trial at a time, it can be harmful to them and to the research.

"When neither researcher knows about the potential interactions with the other trial, that raises concerns about scientific validity," says Simon, who has a doctorate in statistical research. "You don't know how these things might interact. It's asking for trouble."

There are better ways to do research, says Greg Koski, the physician who headed the federal Office of Human Research Protection for two years. Koski says a single U.S. panel should oversee all experimental tests.

The National Bioethics Advisory Commission suggested that informed-consent discussions between researchers and participants be audio- or videotaped to ensure they're done right.

The commission also recommended a system to compensate people for research-related injuries and said all review boards should have to register with the federal government. In addition, it said all review-boards members should be trained in research ethics.

Mark Yessian, who oversaw investigative reports on review boards over the past decade as Boston's regional inspector general for the Department of Health and Human Services, says changes are needed.

"The drug industry is trying to bring products to market," says Yessian, who retired last month. "We don't want to suffocate that, but we need to do it in a more balanced way to give subjects confidence that there are people looking out for their interests."

Koski says the mission won't be easy. "It's not really a 'few bad apples' problem," he says. "We need to create a system that grows better apples."