Private tests a risky business
A seven-member panel working for the world's largest company overseeing protection of people in clinical trials met on the morning of Nov...
A seven-member panel working for the world's largest company overseeing protection of people in clinical trials met on the morning of Nov. 20, 2004, to review recruiting material for a proposed drug test at Johns Hopkins School of Medicine in Baltimore.
One of the members, a doctor, said she didn't understand the recruiting script aimed at the public. The board voted to approve the document anyway.
The panel was part of Western Institutional Review Board (WIRB), a for-profit company that's paid by pharmaceutical companies.
The U.S. Food and Drug Administration has farmed out much of the oversight for protecting people in tests to private companies such as Western. WIRB monitors clinical trials for more than half the new drugs submitted each year to the FDA.
"This whole world gives me hives, this privatized review process," says Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania in Philadelphia. "They've had conflicts of interest since the beginning."
The world's largest pharmaceutical companies outsource 75 percent of experimental drug testing to private companies paid by drug makers.
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.
Western, an Olympia company, is responsible for protecting people in 17,000 clinical trials in the U.S. and is the oldest company of its kind. President Angela Bowen, an endocrinologist, founded it in 1977.
In the 1990s, the company oversaw tests in California and Georgia 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.
Joanne Rhoads, the physician who directs the FDA's Division of Scientific Investigations, says the agency doesn't have enough staff members to aggressively monitor trials, 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."
Like most private companies hired to oversee protection of people in drug tests, WIRB is secretive. It doesn't make public the names of its members or the names of the pharmaceutical companies whose tests it monitors.
The decision by the WIRB panel at Johns Hopkins comes from minutes of the meeting made available by the school because Maryland state law requires such public disclosure. WIRB deleted all names and many details before allowing Bloomberg News to review the minutes.
Plans to visit sites
WIRB aims to visit test sites it monitors once every three years, Bowen says. She says WIRB is the best in the industry because of the professionalism of her members, their training and expertise and their willingness to turn down drug company tests they don't approve.
Harvard Medical School Senior Dean Daniel Federman sees WIRB differently. "If you listen to themselves talk about themselves, you get a whitewash," he says.
In the 1990s, WIRB oversaw 23 clinical trials conducted by Robert Fiddes, a Los Angeles doctor who was charged with lying to the FDA.
The FDA's investigation found that Fiddes repeatedly fabricated data and improperly included employees and family members in trials.
He pleaded guilty in 1997 and was sentenced to 15 months in federal prison.
A 1999 FDA inspection report criticized WIRB for its role in the doctor's experiments. "There is a failure to have complete documentation of the board's knowledge, discussion and decisions regarding research activities," FDA investigators wrote of WIRB.
Bowen says WIRB didn't know about Fiddes's fraud. "He fooled everybody," she says.
'I call them clueless'
Pharmaceutical firms would be amazed at how poorly some clinical tests are run, she says. "Some of the companies would be embarrassed if they saw the quality of the people doing research," she says. "I call them clueless."
WIRB has 250 employees, who refer to themselves as "Wirbies," and about 100 review-board members.
Bowen, who used to be president of a drug company called William P. Poythress in Richmond, Va., says Western had $20 million in revenue in 2004. It has grown about 20 percent a year for the past decade, Bowen says.
Review-board members attend about 40 four-hour meetings each month to approve new experiments and trial-recruiting materials, review tests and examine reports of serious side effects, Bowen says. Those meetings are attended by review board members or alternates.
About 60 items are considered at each meeting, giving members an average of four minutes to discuss each issue. The meetings and their minutes are closed to the public, as are the names of the board's members.
"If you were a plaintiff's lawyer, wouldn't you like to have the identities of all the membership?" Bowen asks.
Computer system lacking
The FDA most recently inspected WIRB in August 2002. The agency found WIRB's computer system lacked an audit function, meaning data entered could be altered without a record of the changes. The FDA called that a "significant objectionable condition."
The FDA inspection in 1999 also criticized WIRB's role in the case of Richard Borison, a Georgia doctor convicted in 1998 of stealing more than $10 million of drug-research money in experimental tests and sentenced to 15 years in state prison.
In 1990, Borison, the chairman of the psychiatry department at the Medical College of Georgia in Augusta, hired WIRB to oversee his experiments with psychiatric drugs. During the time WIRB was monitoring him, Borison stole the money provided for clinical trials by Pfizer, Wyeth and Novartis AG.
As a department chairman, Borison was required by college rules to use the school's review board. Instead, the doctor used WIRB, 2,300 miles away.
"Borison bypassed us and went to WIRB," says George Schuster, chairman of the college's review board. "We didn't know until the whole thing blew up that they were using WIRB. If WIRB had followed its own rules, we'd have notified them it wasn't acceptable. We wouldn't have allowed the fraud to continue."
WIRB's rules required it to notify a school when it was hired to oversee research. Bowen says WIRB didn't inform the Medical College of Georgia because Borison had told WIRB he was a part-time professor.
Letters from Borison to WIRB were on the school's letterhead, listing Borison as chairman of the psychiatry department.
In his indictment, Borison was also accused of endangering the lives of participants by using inadequately trained employees and permitting his signature to be forged on prescriptions.
An FDA inspection report of Borison in 1997 also detailed patient-protection violations, finding that untrained employees administered experimental drugs, evaluated side effects and decided when to increase dosages.
The FDA sent its findings to WIRB, which had allowed Borison's tests to proceed for six years.
Today, seven years after Borison's conviction, Bowen says WIRB did nothing wrong in its oversight of the Georgia tests. "I didn't see that there were patient-safety issues," says Bowen, who sat on the panel that oversaw Borison's experiments.
WIRB told its staffers to send research approvals directly to Borison's home and not to the school, according to WIRB documents obtained by state prosecutors.
An undated WIRB memo says, "Arrangement with Dr. Borison is to have all correspondence sent to his home address."
Bowen says WIRB clients are free to use any address. "We send it to where they ask us to," she says. "We didn't know it was his residence."
Prosecutor David McLaughlin of the Georgia Attorney General's Office in Atlanta says he was astonished by Bowen's attitude about Borison.
"I'm a prosecutor, sitting in her office, telling her they did this and that, and she was saying, 'It's not a problem for us,' " he says. "That's just bogus. I had such a bad taste in my mouth when I left."
The state brought no charges against WIRB.
Pfizer spokesman Stephen Lederer says the results of Borison's research were removed from Pfizer's database and weren't sent to the FDA. Wyeth spokesman Gerald Burr declined to comment.
In 2001, WIRB was hired by Johns Hopkins School of Medicine to help review research at the school after a clinical trial participant died in the same year.
Minutes of WIRB meetings show the board complained that it took seven weeks for WIRB's staff members to inform the board of the death of five people in a clinical trial.
For the Johns Hopkins review, WIRB's nine-member panels often met with just five members present, the minutes show. Alternate members made up the majority of WIRB boards 20 times from Jan. 1 to March 31, 2004. Twice in three months, all of the members were alternates.
In 2003, the Hopkins minutes show, WIRB required a clinical-trial sponsor to make changes in the recruiting materials for a trial to better protect participants in the experiments. The sponsor, whose name was deleted from the minutes by WIRB, asked WIRB to reconsider its decision.
On Feb. 26, 2004, the same WIRB panel, acting with four alternates and one of its regular members present, reversed its decision and allowed the company to keep its original proposed language.
"That was worrisome," Bowen says, after being informed of what had happened. "I wish somebody had caught it sooner."
Daniel Ford, vice dean for research at Johns Hopkins School of Medicine, says the reversal by WIRB concerns him. "It's possible you could have manipulation," he says. "One of the big things WIRB sells is speedy review."
Ford says WIRB provides high-quality service.
The University of Pennsylvania's Caplan disagrees. He says WIRB has failed to protect participants in clinical trials. "That's just what you fear from commercial IRBs," he says. "They've had conflicts of interest since the beginning."
In a 2002 Seton Hall Law Review article, WIRB's director of regulatory affairs wrote that there's an inherent conflict within independent review boards because their fees come from the same pharmaceuticals whose trials they're asked to monitor. "The conflict of interest faced by independent IRBs is real and substantial," David Forster wrote.
"Independent IRBs are paid by sponsors and investigators to protect subjects who are participating in research conducted by those sponsors and investigators," Forster wrote.
There aren't any federal rules requiring for-profit IRBs, which are often thousands of miles away from trial sites, to visit or inspect the test center at any time.
Nobody has ever studied the effectiveness of review boards or tracked how many people are injured or killed each year while participating in clinical trials, says Harvard's Federman, who was chairman of a national committee on clinical trial safety in 2003.
"An intelligent person would assume we know this," Federman says. "We don't know the number of persons harmed in clinical trials each year and are missing a registry of all subjects that participate in trials."