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Acting on information provided by the FDA's criminal investigators, the U.S. Attorney's Office in Birmingham indicted Dr. Campbell on 21 counts of fraud. She pleaded guilty to one count of mail fraud and was sentenced to 57 months in prison.
In a phone interview from the federal prison in Lexington, Ky., Campbell admitted that she forged a consent form but declined to discuss other allegations of wrongdoing. Instead, Campbell, now 49, blamed the drug manufacturer for fast-tracking the trial.
"They seemed to want to rush you through everything, " said Campbell, who had performed a half-dozen clinical trials for other drugmakers. "They didn't care how you did it. They wanted the trial over so they could get the data to the FDA."
Despite Campbell's "deviations" during the Ketek trial, once it was over Aventis hired her for a second study that spring. The drugmaker also flew Campbell to a conference in San Diego that summer so she could learn how to market Ketek to other physicians.
In the fall of 2002, when the FDA called to schedule a routine audit, Campbell said, Aventis told her to delay the agent for a week.
"Then they flew in two doctors to prep me and four to six girls to go through my files, " said Campbell, who said the drug company's representatives suggested appropriate responses to the FDA's queries.
Sanofi-Aventis' spokeswoman said it is normal for a drug company to help a doctor prepare for a site inspection. She said Campbell was advised to answer the FDA's questions truthfully. The drugmaker ended its relationship with the doctor after the FDA initiated its criminal investigation, she added.
Campbell said she was amazed when the court said the drugmaker was a victim of her fraud and ordered her to pay $925, 000 restitution. In a court filing last year, Campbell appealed the restitution order.
Aventis "had been made aware of the fraud at my site by PPD, " she argued. "At NO TIME did they (Aventis) attempt to stop my participation."
Late last month, Campbell's motion was denied.
* * *
Ketek is the latest in a string of drug debacles that have tarnished the FDA. Testifying with Ross and Cisneros at a congressional hearing in February, a veteran FDA epidemiologist put the drug's history into perspective.
"The Ketek story is about the FDA's betrayal of the public trust, " said Dr. David Graham, who has been with the agency for 23 years. "Unfortunately, Ketek is not an anomaly."
Safety recalls of medicines are occurring at twice the rate this decade as in the 1990s, with the 2004 withdrawal of Merck's Vioxx the best-known example. Also on the rise: relabeling drugs to include deadly side effects.
Ross, the FDA safety reviewer, ended a 10-year career with the agency in November and now is an assistant clinical professor of medicine at George Washington University in Washington, D.C. He said the agency's growing reliance on industry dollars has fostered a "culture of approval."
Last year drugmakers paid the FDA more than $300-million in user fees, accounting for more than half of the agency's drug review budget.
"Even if a product doesn't work or we don't know how it works, there is pressure on managers that gets transmitted down to reviewers to find some way of approving it, " Ross said. "There's been a cultural shift at the FDA, and the pharmaceutical industry is now viewed as the client."
Ross, an infectious disease specialist, stressed that Ketek was being marketed for common ailments that often get better over time without the use of antibiotics. "This was not a drug that anybody thought was necessary in terms of public health. But it was important for the company financially."
Cisneros, who continues to work as a clinical trial monitor, is waiting for someone other than Campbell to be held accountable for how the Ketek study was mishandled.
"We're all just afraid nothing will come of this, " she said. "But the system is going to spiral out of control. It's already teetering."
* * *
In mid December, an FDA advisory committee discussed the growing evidence linking Ketek to liver failure: 53 reported cases, including two people who needed liver transplants and five deaths.
Among them was Obrajero, who left behind two young daughters. His widow, distraught that a 26-year-old who rode motorbikes and played soccer could be killed by a cold, sought out a lawyer. She was unaware that his case, along with two other Ketek-related liver injuries treated within a few months at the same hospital, had been reported to the FDA and written up for a medical journal.
The lawyer, Neal Rodgers of Charlotte, said he thought he had a routine medical malpractice case until his researcher stumbled on the article in the Annals of Internal Medicine.
"She said, 'You won't believe it. This guy's autopsy is all over the Internet, ' " said Rodgers, who sued Sanofi-Aventis, PPD, Campbell and three other doctors involved in Study 3014.
Dr. William Lee, an FDA consultant and advisory committee member, said only 10 percent to 12 percent of drug-related adverse events are reported, so the full impact of Ketek may never be known.
"But the drug probably should not be used as a daily antibiotic, which is how they'd love to market it, " said Lee, director of the Clinical Center for Liver Diseases at the University of Texas Southwestern Medical Center in Dallas.
On Feb. 12, the day before the congressional hearing on Ketek, the FDA sharply curbed the drug's use. With health risks outweighing the benefits of using the drug for common colds, the agency limited Ketek's use to treatment of community-acquired pneumonia.
Until then, Ketek had been one of the most successful antibiotic launches in history, bringing Sanofi-Aventis nearly $400-million in U.S. sales.
Since the FDA restricted its use, Ketek sales have dropped by half.
Times researcher Carolyn Edds contributed to this report. Kris Hundley can be reached at email@example.com
or (727) 892-2996.
Clinical research study or clinical trial:
The testing of an experimental drug or device in humans for safety and/or efficacy
Contract research organizations:
Companies that manage all or part of the clinical trial process for pharmaceutical and biotech companies
Institutional review boards:
Examine a clinical trial's protocol to ensure that the patient's rights are protected, and that the study does not present an undue or unnecessary risk to the patient
22 Number of drugs approved by the FDA in 2006
6 months Average FDA review time for priority drugs in 2006
21 months Average FDA review time for priority drugs in 1993*
10 months Average FDA review time for standard drugs in 2006
27 months Average FDA review time for standard drugs in '93*
* First full year in which the pharmaceutical industry paid user fees to the FDA in return for speedier drug approvals. Sources: FDA, U.S. Government Accountability Office
Use: Originally approved for acute sinusitis and chronic bronchitis as well as community-acquired pneumonia. In February, the FDA limited its use to pneumonia.
Manufacturer: Sanofi-Aventis, Paris.
Type of drug: Antibiotic (telithromycin).
FDA approval: April 1, 2004.
Potential side effects: Liver injury, loss of consciousness, visual disturbances; not to be taken by people with myasthenia gravis (a muscle disease).
U.S. sales through 2006: $374-million.
U.S. prescriptions through 2006: 6.1-million.
Estimated loss due to restrictions on use: $575-million.
Sources: U.S. Food and Drug Administration, IMS Health, Sanofi-Aventis