Off Topic: Bloomberg News Investigation an Eye Opener - Drug Industry Human Testing Masks Death, Injury, Compliant FDA, Nov 2, 2005

[Guest guest]

Drug Industry Human Testing Masks Death, Injury, Compliant FDA Reporters: , Mike , Liz Willen

Nov. 2 (Bloomberg) -- 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 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 like 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 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.''

`I'm in a Bind'

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 Big Pharma, the name for the world's largest pharmaceutical companies, hopes 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.''

Conflicts of Interest

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 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 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.

`It's an Eye-Opener'

``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.''

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 Federman, a doctor who is a senior dean of Harvard Medical School in Boston.

The chief executive officers of drug companies should be held accountable for any lack of ethics in these tests, he says.

``The CEOs of the companies have to be publicly, explicitly and financially responsible for the ethical approach,'' says Federman, 77, who still sees patients. ``It's not possible to insist on ethical standards unless the company providing the money does so.''

Pressure for New Drugs

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

Faced with the expiration of patents on best-selling drugs like AstraZeneca Plc'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.

Oversight Secrecy

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 private independent review board companies that oversee drug trials operate in such secrecy that the names of their members often aren't disclosed to the public.

The oldest and largest review company is Western IRB, founded in 1977 by Bowen, an endocrinologist. WIRB, an Olympia, Washington-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.

Unlicensed Employees

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 that the facility 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 test center 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 E. Shamblen, 67, SFBC's vice president of clinical operations. Both Shamblens declined to comment.

`Gives Me Hives'

SFBC's 2005 shareholder proxy, filed with the U.S. Securities and Exchange Commission, lists 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.

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 Washington-based trade association and lobbying group, says human drug tests in the U.S. are safe and well-monitored.

`Gold Standard'

``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 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.''

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.

`Stopped Enforcing Rules'

``The FDA's backbone has been Jell-O,'' says Hensley, 60, who's now president of Chapel Hill, North Carolina-based Hensley & Pilc Inc., which advises pharmaceutical companies on FDA compliance. ``The folks at the FDA stopped enforcing the rules several years ago.''

By law, drug companies must first conduct tests to determine whether potential drugs produce dangerous side effects, such as organ damage, impaired vision or difficulty breathing. The FDA calls them phase I tests.

In 1991, 80 percent of industry-sponsored drug trials were conducted by medical faculty at universities, with protection for participants provided by the schools' 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.

`No Qualifications'

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 prohibits people from taking part in two clinical trials at the same time.

Multiple Trials

o Alvarez, 36, an Argentine in the U.S. on a visa; Efrain Sosa, 35, a Cuban native; and Marlon Matos, a 27-year-old immigrant from Venezuela, say they've participated in more than one clinical trial in Miami at the same time or gone from one test to another, ignoring required waiting periods.

They say they do it for the money, without telling the test centers, and that no one has ever caught them violating the rule.

``We maintain many safeguards to help us ensure that the participants of our clinical trials are not participating simultaneously in multiple clinical trials,'' SFBC's Hantman says.

SFBC fingerprints participants to keep track of their tests at the company, he says. ``Unfortunately, there is no clearing house that we're aware of that would allow us to find if they were participating in another trial at the same time,'' he says.

In April, Alvarez signed up for a 36-day clinical trial at Miami testing company Elite Research Institute for a new sustained-release form of donepezil, an Alzheimer's drug that Tokyo-based Eisai Co. sells in the U.S. with New York-based Pfizer.

`I Hop Around'

At the time, Alvarez was in the middle of a 212-day test sponsored by Madison, New Jersey-based Wyeth at SFBC for an experimental muscular dystrophy drug, according to consent forms he signed.

``I hop around to get around that,'' says Alvarez, a part- time construction worker who's wearing a black T-shirt and jeans when he's interviewed in a bagel shop two doors down from SFBC. ``They ask, but I just don't tell them. Everybody does that.''

Steve Simon, a research biostatistician at Children's Mercy Hospital in Kansas City, Missouri, says that when people participate in more than one clinical trial at a time, it can be harmful to people and research.

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

Carefully Planned

Ernesto Fuentes, Elite's clinical trial director, didn't return calls for comment. Eisai spokeswoman Judee Shuler says Elite did everything it could to ensure participants in the clinical trial weren't in other tests at the same time, including asking subjects verbally if they were.

Pfizer spokesman Lederer says his company had no role in the donepezil tests. Gerald Burr, a Wyeth spokesman, says the company carefully planned and monitored the clinical trial.

The FDA requires pharmaceutical companies to hire monitors to audit clinical trials to ensure patient safety and scientific validity. ``Our sponsors visit our facilities frequently to monitor our trials and also routinely audit our work,'' SFBC's Hantman says.

Pharmaceutical company monitors spend more time scrutinizing data being gathered than watching out for people's safety, Harvard's Federman says. ``There are no monitors of monitors,'' he says. ``It's like looking at a dark cloud. There's minimum training. They're relying on people running the trials.''

This extract represents about a third of this story. To read the complete Bloomberg article: http://quote.bloomberg.com/apps/news?pid=10000006 & sid=aspHJ_sFen1s & refer=home