'PPD knew about Ketek clinical trial fraud' - claims former employee

Ann Marie Cisneros, a former member of staff of PPD, was speaking as a witness at a hearing on the adequacy of the FDA to assure the safety of the drug supply, before the House Committee on Energy and Commerce members.

In her testimony last Tuesday, she said that both her former employer PPD and Sanofi-Aventis knew that there were discrepancies in the clinical trial data included in the study 3014 of Ketek (telithromycin) and there were also problems at the site but said neither of the companies took any action.

Outsourcing-Pharma.com made several attempts to reach PPD but the company was unavailable to comment.

Study 3014 was a postmarketing study carried out between November 2001 and March 2002 on behalf of Aventis by PPD, after the FDA said that it needed more safety information on Ketek following fears that it could cause liver problems.

The study was allegedly riddled with fraud, including unscrupulous patient recruitment by some of the enrolling doctors and significant under reporting of adverse events.

Dr Anne Kirkman-Campbell, the investigator at the highest enrolling site during study 3014 was found guilty of conducting fraud with the enrolment of patients and faking consent forms and was sentenced on 24 March 2004 to 57 months in prison, fined $557,251 (€423,636), and ordered to reimburse Aventis $925,774.

Cisneros was a clinical research associate (CRA) for PPD and tasked to assist with the monitoring of Dr Kirkman-Campbell's site.

"From what I observed, Dr Kirkman-Campbell indeed had engaged in fraud," she said during last week's hearing.

"But what the court that sentenced her did not know is that Aventis was not a victim of this fraud.

On the contrary."

"I knew it, PPD knew it, and Aventis knew it," said Cisneros.

She added that even before conducting the Kirkman-Campbell site, a number of "red flags" were apparent.

For example, over 400 patients had been enrolled, while Aventis was paying Dr Kirkman-Campbell $400 per patient.

By comparison, another site in Gadsden had enrolled just 12 patients.

In addition, no patients had withdrawn from the study and none of them were lost to follow up, "an unusual occurrence given the number of subjects", she said.

Sanofi-Aventis said its predecessor Aventis was not aware of the fraud until after it had submitted Study 3014 to the FDA.

"It was only after FDA criminal investigators conducted an evaluation, having tools at their disposal that may not be available to study sponsors, that the fraud was discovered," said the company in a statement.

Last week, on the eve of Cisneros' testimony, the FDA announced it had restricted the use of the drug in the US to treat pneumonia and not less serious illnesses.

Since its approval in 2004, more than five million prescriptions for Ketek have been issued in the US.

Since then, 14 patients have suffered liver failure after taking Ketek and at least four of them have died.

23 others have suffered serious liver injury.

In addition to liver problems, Ketek has been known to cause blurred vision and loss of consciousness.

Most of the reported problems involving Ketek occurred in otherwise healthy patients.

The new FDA restrictions could hit hard Aventis since 70 per cent of Ketek's $264m sales in 2005 came from the US, according to Pharmaceutical Business Review.

Last year, Sanofi-Aventis stopped disclosing Ketek's sales separately but Datamonitor estimates that sales of the drug, which decreased in 2006, will struggle to pick up after the FDA's verdict.