Clinical study. Clinical trial. Clinical protocol. They all mean the same thing — a scientific study of how a new medicine or treatment works in people. Through clinical studies, doctors find new and better ways to prevent, detect, diagnose, control, and treat illnesses.
Many new medicines and treatments are found to be helpful and safe in test tubes and in animals. They must also prove safe and effective in humans before doctors can prescribe them. This testing in humans is permitted only if that person volunteers for participation and understands the risks and benefits of taking part in a study. This informed consent to participate must be based on the volunteer's understanding of what is involved in the study, including potential risks and benefits. Volunteers may leave a study at any time.
Medical researchers depend on both healthy and sick people to volunteer for studies that slowly change the way medicine is practiced.
Many times, those who have tried and failed every approved therapy desperately search for experimental treatments as a last hope.
But Nancy King, a lawyer and medical ethicist at UNC Chapel Hill, cautions that volunteers should not confuse research with treatment.
"People shouldn't really enroll in research expecting that they're going to benefit," King said. "Most things that are being studied don't pan out. Many things that make it onto the market have significant risks. There's no such thing as a safe drug."
For example, "Many people with HIV and AIDS enroll in drug studies so they can afford the multiple and expensive drugs they need to stay well," King said. But even if the trials are beneficial, they only last for so long. "Then what happens?"
"A good, honest consent form is going to say `This is really about future patients and not about you,' " King said. "If people do participate, they ought to be doing so out of altruism."
The fast-growing interest in genetics raises other questions about what researchers can do with the specimens of saliva, blood and tissue they collect from volunteers.
King cites the case of the Havasupai, a small Indian nation in northern Arizona.
In the 1990s, tribal members allowed an Arizona State University anthropologist to collect blood samples to help understand their rising incidence of diabetes.
Years later, the tribe learned its samples had been used to study schizophrenia, inbreeding and migration patterns without additional consent.
The migration studies in particular offended tribe members who traced their origins to the Grand Canyon. The studies concluded Indians had migrated from Asia.
Last year, the tribe sued Arizona State, the University of Arizona and Stanford University, alleging the schools allowed professors to abuse their authority and bypass laws protecting the tribe by using information from the samples.
The case raises many interesting questions, King said.
"Suppose we just tell people we're going to use (specimens) for anything we can think of? Does that make it OK?"
"If you're a graduate student asked to work on a research project, what kinds of questions should you be asking your mentor?"
As a patient or caregiver what questions would you be asking?
November 6, 2005 - 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 his wife and four children 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 Inc.'s test center, which, with 675 beds, is the largest for-profit drug testing center in North America.
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 motel.
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 like SFBC, a leader in the 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 be dangerous, and sometimes 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."
Inside the Miami testing center, the brown paint and linoleum is 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."
Every year, Big Pharma, as the world's largest drugmakers are called, spends $14 billion to test experimental drugs on humans.
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, drugmakers 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, riddled with conflicts of interest -- and sometimes deadly. Every year, trial participants are injured or killed.
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.
But the institutional review boards, or IRBs, that oversee drug company trials operate in such secrecy that the names of their members often aren't disclosed to the public.
The chief executive officers of drug companies should be held accountable for any lack of ethics in these tests, says Federman, who chaired a national committee on clinical trial safety in 2003. CEOs of 15 pharmaceutical companies that outsource drug testing to firms including SFBC -- among them, Pfizer Inc., 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, 56, says. "We are committed to conducting research that fully complies with industry and regulatory standards."
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, 48, wife of Cooper Shamblen, 67, SFBC's vice president of clinical operations. Both Shamblens declined to comment.
SFBC's 2005 shareholder proxy, filed with the U.S. Securities and Exchange Commission, lists Lisa Krinsky as its chairman 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.
The drug experiment 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 Marcia Angell, the former New England Journal of Medicine editor.
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 themselves 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 say 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, 50, who has a doctorate in philosophy, 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."
The Pharmaceutical Research and Manufacturers of America, a Washington-based trade association and lobbying group, 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. "What the FDA regulations require is not any gold standard for trials," Rhoads, 55, says.
The agency doesn't have enough staff to monitor trials aggressively, 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," she 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. Families of injured or dead trial participants seeking accountability for mistakes have to file lawsuits.
"The FDA's backbone has been Jell-O," says Hensley, 60, now president of Chapel Hill-based Hensley & Pilc Inc., which advises pharmaceutical companies on FDA compliance. "The folks at the FDA stopped enforcing the rules several years ago."
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.
Mark Yessian, who oversaw investigative reports on IRBs 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 in October. "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."
The world's largest pharmaceutical companies outsource 75 percent of experimental drug testing to private companies that are paid by drugmakers. Every year, scores of people in the U.S. are injured and killed in clinical trials, while receiving little or no medical care.
Unable to oversee human safety in most clinical trials in the U.S. by itself, the FDA has left much of the job to for- profit review boards.