15 Apr (PROPUBLICA) – On the morning of May 3, 2010, three agents of the Food and Drug Administration descended upon the Houston office of Cetero Research, a firm that conducted research for drug companies worldwide. Lead agent Patrick Stone, now retired from the FDA, had visited the Houston lab many times over the previous decade for routine inspections. This time was different. His team was there to investigate a former employee’s allegation that the company had tampered with records and manipulated test data. By Rob Garver and Charles Seife, Special to ProPublica
See Chart of the Five Drugs the FDA doesn’t want you to know relied on tainted Data.
When Stone explained the gravity of the inquiry to Chinna Pamidi, the testing facility’s president, the Cetero executive made a brief phone call. Moments later, employees rolled in eight flatbed carts, each double-stacked with file boxes. The documents represented five years of data from some 1,400 drug trials.
Pamidi bluntly acknowledged that much of the lab’s work was fraudulent, Stone said. “You got us,” Stone recalled him saying.
Based partly on records in the file boxes, the FDA eventually concluded that the lab’s violations were so “egregious” and of such a “pervasive nature” that studies conducted there between April 2005 and August 2009 might be worthless.
The health threat was potentially serious: About 100 drugs, including sophisticated chemotherapy compounds and addictive prescription painkillers, had been approved for sale in the United States at least in part on the strength of Cetero Houston’s tainted tests. The vast majority, 81, were generic versions of brand-name drugs on which Cetero scientists had often run critical tests to determine whether the copies did, in fact, act the same in the body as the originals. For example, one of these generic drugs was ibuprofen, sold as gelatin capsules by one of the nation’s largest grocery-store chains for months before the FDA received assurance they were safe.
The rest were new medications that required so much research to win approval that the FDA says Cetero’s tests were rarely crucial.
Stone said he expected the FDA to move swiftly to compel new testing and to publicly warn patients and doctors.
- In 2011, the FDA announced years’ worth of studies from a major drug research lab were potentially worthless.
- About 100 drugs were on the U.S. market based in part on these tests.
- The FDA let the drugs stay on pharmacy shelves with no new testing (in some cases until now).
- As the FDA investigated and ordered re-tests, its European equivalent pulled seven drugs from the market.
- The FDA says it has no evidence that any of the drugs were unsafe or that any patient has been harmed.
- The FDA has never named the drugs, saying to do so would reveal trade secrets.
Instead, the agency decided to handle the matter quietly, evaluating the medicines with virtually no public disclosure of what it had discovered. It pulled none of the drugs from the market, even temporarily, letting consumers take the ibuprofen and other medicines it no longer knew for sure were safe and effective. To this day, some drugs remain on the market despite the FDA having no additional scientific evidence to back up the safety and efficacy of these drugs.
By contrast, the FDA’s transatlantic counterpart, the European Medicines Agency, has pulled seven Cetero-tested medicines from the market. The FDA also has moved slowly to shore up the science behind the drugs. Twice the FDA announced it was requiring drug makers to repeat, reanalyze or audit many of Cetero’s tests, and to submit their findings to the agency. Both times the agency set deadlines, yet it has allowed some companies to blow by them.
Today, six months after the last of those deadlines expired and almost three years after Cetero’s misconduct was discovered, the FDA has received the required submissions for just 53 drugs. The agency says most companies met the deadlines but acknowledged that “a few have not yet submitted new studies .”
Other companies, it said, have not submitted new research because they removed their drugs from the market altogether. For its part, the FDA has finished its review of just 21 of the 53 submissions it has received, raising the possibility that patients are taking medications today that the agency might pull off the market tomorrow. To this day, the agency refuses to disclose the names of the drugs it is reassessing, on the grounds that doing so would expose “confidential commercial information.” ProPublica managed to identify five drugs  that used Cetero tests to help win FDA approval.
FDA officials defended the agency’s handling of the Cetero case as prudent and scientifically sound, noting that the agency has found no discrepancies between any original drug and its generic copy and no sign that any patients have been harmed.
“It is non-trivial to have to redo all this, to withdraw drugs, to alarm the public and the providers for a large range of drugs,” said Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research. “There are consequences. To repeat the studies requires human experimentation, and that is not totally without risk.”
Woodcock added that an agency risk assessment found the potential for harm from drugs tested by Cetero to be “quite low,” an assessment she said has been “confirmed” by the fact that no problems have been found in the drugs the agency has finished reviewing. She declined to release the risk assessment or detail its design. A subsequent statement from the agency described the assessment as “fluid” and “ongoing.” The FDA also has not released its 21 completed reviews, which ProPublica has requested.
Some experts say that by withholding so much information in the Cetero case the FDA failed to meet its obligations to the public.
“If there are problems with the scientific studies, as there have been in this case, then the FDA’s review of those problems needs to be transparent,” said David Kessler, who headed the FDA from 1990 to 1997 and who is now a professor at the University of California at San Francisco. Putting its reviews in public view would let the medical community “understand the basis for the agency’s actions,” he said. “FDA may be right here, but if it wants public confidence, they should be transparent. Otherwise it’s just a black box.”
Another former senior FDA official, who spoke on condition of anonymity, also felt the FDA had moved too slowly and secretively. “They’re keeping it all in the dark. It’s not transparent at all,” he said.
By contrast, the European Medicines Agency has provided a public accounting of the science behind all the drugs it has reviewed. Its policy, the EMA said in response to questions, is to make public “all review procedures where the benefit-risk balance of a medicine is under scrutiny.”
Woodcock dismissed comparisons to the EMA.
“Europe had a smaller handful of drugs,” she said, “and they may not have engaged in as extensive negotiation and investigations with the company as we did.” She said the FDA would have disclosed more, including the names of drugs, had it believed there was a risk to public health. “We believe that this did not rise to the level where the public should be notified,” she said. “We felt it would result in misunderstanding and inappropriate actions.”
In a written response to Kessler’s comments, the FDA said,
“We’ve been as transparent as possible given the legal protections surrounding an FDA investigation of this or any type. The issue is not a lack of transparency but rather the difficulty of explaining why the problems we identified at Cetero, which on their face would appear to be highly significant in terms of patient risk, fortunately were not.”
Still, the FDA’s secrecy has had other ramifications. Some of Cetero’s suspect research made its way unchallenged into the peer-reviewed scientific literature on which the medical community relies. In one case, a researcher and a journal editor told ProPublica they had no idea the Cetero tests had been called into doubt.
For complete article go to Propublica.
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