Sunday, May 27, 2007

Sanofi Aventis - Ketek: anatomy of a fraud

Dr. Campbell got greedy.

The drugmaker was offering doctors $400 per patient to test Ketek, its new antibiotic for persistent colds and coughs.

Anne Kirkman Campbell, a family practice doctor in Gadsden, Ala., signed up 400 patients, more than any other doctor in the country.

When one patient backed out, Campbell forged the consent form and faked the data. A company hired to oversee the study caught the doctor's forgery, along with unmistakable signs of fraud involving dozens of other patients, and alerted the drugmaker.

But the pharmaceutical company, which stood to make hundreds of millions of dollars on Ketek, didn't stop Campbell or report her crime to the Food and Drug Administration. Instead, it included her dubious data in its submission to the agency.

Even after federal regulators stumbled on Campbell's fraud and uncovered problems at several other study sites, the FDA approved Ketek.

A system of checks and balances had become one of winks and nods.

Then people started dying of liver failure.

Aventis Pharmaceuticals Inc. thought it had a blockbuster in Ketek pronounced kee-tek. It would be marketed as the next amoxicillin, a widely used antibiotic to treat the sinusitis and bronchitis that plague millions of Americans each year.

But before Ketek could come to market, the FDA required proof that the expensive new drug was at least as good as the existing treatment. So Aventis devised Study 3014, a clinical drug trial involving 1, 800 private physicians and thousands of their patients nationwide.

As is common practice in the industry, Aventis opted to have a third party conduct the study. It paid PPD Inc., one of the world's biggest contract research organizations, some $20-million for the work.

Ann Marie Cisneros had worked for PPD for three years when she was sent to check up on Campbell in early 2002. The doctor had recruited more than 1 percent of Gadsden's adult population for the Ketek study.

Cisneros noticed that none of the doctor's staff would look her in the eye. Combing patient files, Cisneros found that the doctor had enrolled her entire staff and several family members in the study.

Patient consent forms had been signed every few minutes and at times when the office was closed. Medical records had been edited, with notations of "sinusitis" and "bronchitis" added so patients would qualify for the trial.

"It appeared the patient was coming into the office for one condition and the doctor was writing in something else later, " Cisneros said. "That's how Dr. Campbell ended up with 407 people."
By comparison, another local doctor found only 12 patients who met the study criteria.

The Ketek study was demanding; it required that patients come in for three office visits and blood draws over five months. But not a single one of Campbell's patients had dropped out.
"That just doesn't happen, period, " said Cisneros, noting that even small studies experience dropouts.

The doctor didn't appreciate the scrutiny. She told Cisneros that she wouldn't have enrolled so many patients had she known it would trigger an audit.

"That's just scary, " Cisneros said. "Dr. Campbell didn't get away with it because she hadn't learned the system."

Certain she had found fraud, Cisneros called her manager at PPD. She also took the unusual step of contacting a consulting partner responsible for ensuring patient safety in clinical trials.

Copernicus Group IRB, also paid by the drug company, had access to trial subjects' names and phone numbers. Monitors like Cisneros usually had limited identifying information.

"I wanted them to call some patients and see if they'd really agreed to be in the study, " said Cisneros, who suspected patients were enrolled without their knowledge. "But the woman at Copernicus said, 'Let's see what Aventis does about this.' "

Spokeswomen for Copernicus and PPD declined to comment.

After Cisneros returned to PPD, she and her bosses had a teleconference with the drugmaker. She said her concerns about the doctor's conduct, including the likelihood that consent forms had been forged, were ignored.

"I walked away from that meeting very frustrated, " Cisneros said. "I'd never seen a sponsor so lackadaisical about a site."

Read the rest of this great article here.

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