FDA under pressure to clamp down on clinical trial fraud
imminent changes to the way it evaluates clinical trials in an
attempt to clamp down on fraud.
The move comes in the wake of an ongoing government investigation into serious allegations that the FDA approved French firm Avenits's antibiotic drug Ketek despite unresolved questions about the drug's safety and efficacy, with full knowledge that some of the clinical data submitted to support the drug's approval was fraudulent.
The key regulatory change planned by the FDA involves forcing drug firms to immediately notify them if they believe a researcher has committed fraud during a study.
Currently drugs firms are being trusted to remove unreliable data from their new drug applications (NDAs) to the FDA, although they are not required to inform the FDA of any suspected fraudulent activity until they submit the application - sometimes years after the fraud occurred - however, this "honesty system" appears to be failing.
The agency said it will also issue new clarification on which adverse events in trials have to be reported to review boards that monitor studies to protect patients.
"We need to make sure there's the proper oversight and authority over all the parties that are involved in clinical trials," said FDA Deputy Commissioner Janet Woodcock.
Other proposed changes to improve regulation of trials include the standardisation of forms used to collect information and a revision on the rules for how patients qualify for clinical trials.
The regulation tightening aims to restore confidence in the approval of NDAs by the FDA, whose reputation has taken a battering after allegations that the agency colluded with Aventis in the approval of Ketek or in the very least, failed to ensure the integrity of a pivotal study (3014) about the benefits and risks of Ketek.
The FDA is still being investigated over the matter by House Representatives Edward Markey and Henry Waxman, who released a statement in May detailing that: "though the FDA has consistently assured the public of Ketek's safety and efficacy, public documents obtained and examined by Representatives Markey and Waxman's staff indicate that the approval process for this drug was seriously flawed."
Senate Finance Committee Chairman Charles Grassley also issued a statement in May detailing the number of allegations that have come to light regarding the FDA's approval of Ketek.
These include that FDA management accepted the resubmission of an NDA for Ketek, which included fraudulent data in support of approval; presented fraudulent study data to an advisory committee tasked with recommending Ketek's approval or disapproval; and instructed FDA scientists appearing before an advisory committee that they should present fraudulent data because discussing issues regarding data integrity and the conduct of the safety study would not be "productive."
In addition, the FDA are alleged to have approved a paediatric clinical trial, involving infants as young as six-months old, despite concerns related to known toxicities, including hepatic, visual, cardiovascular, and vasculitic adverse events; and continued to knowingly cite the fraudulent study (3014) in publicly released safety information on Ketek.
Internal FDA emails have since surfaced showing that at least four agency safety officials - including Dr Charles Cooper, Dr David Ross and Dr Rosemary Johann-Liang - expressed serious concerns about the safety of Ketek.
"I tried to argue that given Aventis's track record in which they have proven themselves to be nontrustworthy that we have to consider the possibility that they are intentionally doing a poor job of collecting the postmarketing data to protect their drug sales," said one of the emails from Dr Cooper.
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.
Study 3014 was a postmarketing study carried out on behalf of Aventis by contract research organisation PPD, after the FDA's insistence that it needed more safety information on Ketek following suspicions that it could cause liver problems.
The study was allegedly riddled with fraud, including unscrupulous patient recruitment by some of the the enrolling doctors and significant under reporting of adverse events.
