More Corruption in the FDA

(Chapter 22 of ebook) How is it that so much drug related fraud can continue, when the FDA’s job is to prevent it?

It has been discussed that on the black box warning for amphetamines, the FDA avoids directly stating the high potential of these drugs to cause serious cardiovascular events including sudden death. We have seen that the FDA’s black box warning falsely states only misuse as the cause of sudden death, despite the reports of deaths resulting from prescribed doses of amphetamine which caused Canada to recall Adderall in 2005. To which extent is the FDA misleading parents and others to let them risk their children’s or their own lives with harmful drugs?

In February 2007, a Congressional Hearing was held questioning the adequacy of the FDA to assure the safety of the nation’s drug supply.[392] At this Congressional Hearing, Senator Grassley reported a number of problems with the FDA, which he later summarized as follows:

I’ve identified problems at the FDA that consistently fit into a few themes.

First, scientific dissent is discouraged, quashed, and sometimes muzzled inside the Food and Drug Administration. Second, the FDA’s relationship with drug makers is too cozy. The FDA worries about smoothing things over with industry much more than it should with its regulatory responsibilities. Third, inside the FDA there’s widespread fear of retaliation for speaking up about problems. And fourth, the public safety would be better served if the agency was more transparent and forthcoming about drug safety and drug risks.[393]

The transcript of this 2007 Congressional Hearing points out the numerous instances of the FDA’s gross regulatory failure. For example, the FDA’s misconduct for the case of the pain relievers Vioxx and Bextra is stated by Representative Bart Stupak as follows. This example summarizes the FDA’s mode of operation to buy the drug manufacturers time when having to recall harmful blockbuster medications, which the next example about antidepressants will further demonstrate. Representative Stupak explains:

These pain relievers [Vioxx and Bextra] were supposed to be easier on the stomach and not cause ulcers for the chronic users. Post-marketing surveillance revealed serious cardiac side effects. Instead of focusing on these serious side effects, the FDA became entwined in a 14-month battle on how the cardiovascular risks should be labeled. FDA officials sided with the drug manufacturer and down played the warnings and the serious side effects of Vioxx. As a result, the FDA may have allowed thousands of patients to die prematurely because of its failure to believe its own scientist and his post-market surveillance findings.[392]

Vioxx’s manufacturer Merck & Co. was finally fined about $1 billion[394] and Bextra’s manufacturer Pfizer paid $2.3 billion for misbranding medications “with the intent to defraud or mislead.”[395]

Dr. David Graham, associate director for science and medicine in the FDA’s Office of Drug Safety, has made the disturbing statement, “the FDA, as currently configured, is incapable of protecting America against another Vioxx. We are virtually defenseless.”[396] Dr. Graham’s point has been confirmed by investigations such as those about antidepressants described below, which have revealed the FDA’s unwillingness to regulate the industry in a manner almost identical to the case of Vioxx and Bextra.

In 2003, the FDA appointed its medical official Dr. Andrew Mosholder to review the more complete antidepressant trial data the agency had requested from the major manufacturers of these drugs. After his analysis of this more comprehensive data, Dr. Mosholder concluded that antidepressants increase suicide risks in children. Dr. Mosholder informed his supervisors of this conclusion in September 2003 more than a year before the FDA finally issued its black box warning in October 2004, announcing this risk for all antidepressants.[397] Dr. Mosholder was originally scheduled to present his findings at an FDA advisory committee meeting in February 2004. But before this public advisory committee meeting occurred, Dr. Mosholder’s supervisors changed their minds because they disagreed with him. Mosholder states, “alternative conclusions were offered to me which I declined to incorporate into my written document.”[397] His higher-ups then barred him from giving his presentation.

“The first question that this raises is quite simple: Why?” asked Representative Joe Barton at a Congressional Hearing that took place in February 2004.[397] “What was the harm in allowing Dr. Mosholder an opportunity to present his data, his analysis, and his opinion to a group of experts?” emphasized Representative Barton, chairman of the Committee on Energy and Commerce whose subcommittee on Oversight and Investigations accused the FDA of inadequacy.

Approximately three months after Dr. Mosholder announced his supposely wrong conclusion in September 2003, the British equivalent of the FDA (MHRA) announced in December 2003 the banning of all the new generation antidepressants except Prozac for children due to their risk of increasing suicidality in young people. MHRA had come to this conclusion after their own review of the same data that Mosholder had reviewed.[304] [315] [316] But even after the British regulators had confirmed Mosholder’s conclusion, the FDA delayed issuing strong enough warnings. The agency required Mosholder’s conclusions to be unnecessarily re-analyzed, wasting 8 months caught up in trying to better label the misclassified suicidal events found in the trial data.[397] [398] This was what the FDA also did in the case of the deadly medications Vioxx and Bextra.[392]

The antidepressant manufacturers seem to have lobbied the FDA to let them profit from their latest scams which had just greatly expanded their market for their most expensive antidepressants and antipsychotics. The TMAP and TeenScreen scams discussed earlier had been recommended by George W. Bush’s New Freedom Committee on Mental Health in July 2003, two months before Mosholder announced his findings.

“There is something terribly rotten at the FDA” exclaimed Representative Deutsch at the September 2004 Congressional Hearing.[397] “I am appalled but, frankly, not surprised by the systematic efforts of the FDA to suppress information that could have prevented the senseless deaths of too many children,” Representative Bart Stupak also stated.[397]

In the 2004 Congressional Hearing, the representatives also asked the FDA why it had not promptly required the antidepressant labels to reflect the fact that clinical trials could not demonstrate efficacy in children. Representative Greg Walden commented:

Why wouldn’t you put that on the label? Why shouldn’t the label reflect that information? I note that the Advisory Committee just recommended that this labeling change take place, but the point is that the FDA knew about the lack of efficacy in these trials several years ago, and nothing has been done to change the label to inform doctors, patients and parents of this finding.[397]

“Shockingly, the FDA made a deliberate decision to withhold information on the clinical failures from parents as well as pediatricians and other prescribers,” stated Representative Peter Deutsch.[397]

“Today, SSRI’s remain on the market without a clear medical benefit to the patient,” Representative Stupak stated three years later in the 2007 Congressional Hearing.[392]

Congressional investigations have also uncovered some of the unethical tactics that the FDA utilizes to cover up its tracks, which demonstrates how the agency’s mode of operation resembles that of a criminal organization rather than a regulator. At the time that the FDA prevented Dr. Mosholder from presenting his findings about antidepressants, the San Francisco Chronicle found this out and published how the agency had “squelched its own investigator’s report.”[397] [398] The FDA then started an inappropriate internal criminal investigation to find out who had leaked that information to the media. “It is readily apparent that the probe [of this criminal investigation] was not about information but, rather, about intimidation,” told Representative Deutsch at the 2004 hearing. But the FDA’s attempts to cover up its fraudulence does not stop with threatening to criminally penalize those trying to publicize the truth. The agency also attempted to obfuscate the fact that such an inappropriate criminal investigation had been conducted. Right before the 2004 Congressional Hearing started, the FDA tried to get Dr. Mosholder to submit an altered document at the hearing instead of the original document revealing the occurrence of the criminal investigation.[397] After consulting with his lawyer, Dr. Mosholder resisted signing this fake document that was presented to him. Mosholder then explained at the Congressional Hearing how the FDA had fraudulently attempted to replace the original document.

It was also discovered by Senator Grassley that more than 40 employees of the FDA’s Center for Drug Evaluation and Research had been warned in an intimidating e-mail to not communicate directly about “handling the document request on antidepressants,” resulting in “chilling the free exchange of information by and between Congressional staff members and FDA employees.”[399]

In 2003, the FDA went so far as to stop Wyeth Pharmaceuticals from warning about the suicidal thoughts or behavior and hostility caused by their antidepressant Venlafaxine (Effexor).[397] Wyeth Pharmaceuticals had, on their own, made a labeling change for Effexor mentioning the reports of increased suicidal ideation, hostility and self-harm caused by their drug “based on the company’s re-analyses of data from the Effexor pediatric trials.”[397] Wyeth had also sent out a warning letter informing health care professionals about this labeling change in August 2003, telling them that Effexor is “not recommended for use in pediatric patients.”[397] But in March 2003, the FDA asked Wyeth to “remove this stronger labeling.”[397] The FDA mandated Wyeth and other antidepressant makers to all use the same labeling which did not recommend doctors to stop prescribing antidepressants for children but only recommended them to “carefully monitor patients receiving antidepressants for possible worsening of depression or suicidality.”[400] Representative Barton expressed at the 2004 Congressional Hearing:

It is incredible that this agency charged with protecting the public health would stop a company from warning the public about risks associated with the use of its products by children.[397]

Similar to the FDA’s reaction to Mosholder’s conclusion in 2003, in 1991 the agency had also prevented the suicide risks of Zoloft and Paxil from being presented to an advisory committee, despite knowing about these risks for two years.[346] In 1996, the FDA’s drug reviewer James F. Knudsen had again tried to point out the reports of suicidal ideation and behavior in children and adolescents exposed to Zoloft. But his conclusions got supposedly “disputed” by a supervisor and obfuscated as in the Mosholder case.[397] [398]

At the time that the FDA was being questioned by Congress in 2004, it had not yet issued its black box warning, but the FDA’s advisory panel had recommended the agency to do so. Would the FDA have followed this advice or ignored it again if not for the pressure coming from Congress? In the 2004 hearing, Representative Deutsch warned, “I expect that the FDA will tell us at this hearing that it will adopt the recommendations of its Advisory Committee.”[397] To make sure that the FDA would not ignore or further delay implementing the recommendations of its scientific advisors, Senator Grassley also sent the FDA a letter right after the hearing:

I trust that the FDA will very quickly and fully consider the Advisory Committee’s recommendations about the “black box” and “med guides”, before the lives of more children are needlessly lost because parents and others lack adequate, readily understandable information when they most need it.[401]

Thus the FDA was forced to issue the black box warning.

How many more drugs are out there whose warnings are not adequate, or are misleading or missing? How many more deadly or harmful treatments without justifiable benefits continue to fill the shelves of pharmacies? The information below further helps reveal the dreadful reality.

In 2008, nine senior FDA scientists informed the government of the institutional corruption in a series of letters to Congress and to President Obama. The scientists presented their evidence as they asked the government to restructure the FDA.[402] [403] This evidence further confirms that the FDA’s “managers have ordered, intimidated and coerced scientists to manipulate data in violation of the law.”[403] But the politicians have failed to improve things, and the situation remained the same in 2015. This was uncovered by experienced journalist Charles Seife.

Charles Seife, M.S. is a versatile professor, author, journalist, and mathematician all in one, holding an M.S. in journalism from Columbia University and an M.S. in mathematics from Yale. He currently teaches journalism at New York University.[404] In April 2015, Seife published the paper “Research Misconduct Identified by the US Food and Drug Administration – Out of Sight, Out of Mind, Out of the Peer-Reviewed Literature” in JAMA Internal Medicine.[405] In this study, Seife tracked 78 studies in which FDA inspectors had found significant research misconduct including submission of false information, problems with adverse events reporting, inadequate or inaccurate record keeping, protocol violations, and others. Of these 78 papers, 75 never mentioned the objectionable conditions or practices the FDA had determined during its inspections. Siefe reports that “no corrections, retractions, expressions of concern, or other comments acknowledging the key issues determined by the inspection were subsequently published,”[405] allowing physicians and researchers to remain oblivious to the tainted nature and false results of these studies. Siefe concludes:

When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.[405]

This demonstrates the sad reality of how the FDA only appears to be doing its job without yielding actual benefits to physicians and patients.

In February 2015, Seife published another article in the online magazine Slate, which mentions many other cases of the FDA’s misconduct.[406] In two of these cases, the FDA’s inspectors discovered research fraud for the studies done to determine the safety and effectiveness of the anti-blood-clotting agent Rivaroxaban and the antibiotic Ketek. But the FDA’s managers deliberately withheld the evidence of this fraud from their advisory committees, which yielded the approval of these drugs. This resulted in wrongful death lawsuits for Rivaroxaban and reports of liver damage and blurred vision associated with Ketek. When Congress stepped in to investigate the FDA’s misconduct about Ketek, “every excuse under the sun has been used to create roadblocks,” stated Senator Grassley, “even in the face of congressional subpoenas requesting information and access to FDA employees.”[406] Siefe sums up the problem: “the FDA has a history of not notifying the public about the misconduct it finds.”[406]

Seife also mentions in his same 2015 article in Slate that a research firm called Cetero was “caught faking data from more than 1,400 drug trials.” This falsified data was used to supposedly demonstrate the safety and effectiveness of about 100 generic drugs. But even after Cetero’s malpractice was uncovered, Seife found “fraud-tainted data on the FDA approved drug labels” of these generic drugs, misleading physicians and the public about safety and benefits. Additionally, Cetero’s fake data had caused some of these generic drugs to appear more similar to their name brands than they actually were. This was indicated by their bioequivalence rating which the FDA never corrected. Seife then mentions a similar case of fraud committed by a research firm called GVK Biosciences. About 40 drugs were approved and released into the U.S. market as a result of the misconduct of this firm. But the FDA has neither disclosed the names of these drugs nor pulled them off the market after GVK’s fraudulence was uncovered.

Seife summarizes the situation:

Despite being called out numerous times over the years for its bad behavior, including from some very pissed-off members of Congress, the agency is stubbornly resistant to change. It’s a sign that the FDA is deeply captured, drawn firmly into the orbit of the pharmaceutical industry that it’s supposed to regulate. We can no longer hope that the situation will get better without firm action from the legislature.[406]

When the legislature has for decades resisted taking any action and lets the fraud go on, millions of children and adults continue to swallow their harmful medications including addictive Schedule II substances prescribed for misbehaving kids as young as four.

Can conscientious individuals or activist groups be able to help clean up the system without the cooperation of the legislature or the regulators?

Simple Internet searches show that the unethical drug marketing scams demonstrated at are far from being comprehensive.[407] [408] [409] [410] [411] While the prisons are filled with the petty drug dealers not rich enough to buy anyone off, the drug dealers of the medical world keep thriving. When big pharma seems to have tainted almost every institution and formed the world’s deadliest cartel, this may have left no room for cleaning up the system. The consumer fraud or class action suits the present writer encourages can only help a few hurt parties financially, and whistleblower lawsuits may help to some degree to open the public’s eyes. But none of this may be enough defeat the monster which seems to have enough money to ensure its continued prosperity. If this is really the case, the only way out may be to keep educating the public as much as possible about the degradation of today’s medical system, encouraging all to try out scientifically verifiable drug free, natural, or preventive alternative approaches. To let this information reach others by helping improve its ranking, please kindly take a few minutes to leave a review.

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