• US Food & Drug Administration Uses Manual Entry Of Data From Clinical Trials To Hide Unsafe Drugs (GAO Report)

    Posted February 5, 2016: by Bill Sardi

    The U.S. Food & Drug Administration (FDA) is loath to monitor the safety of drugs following their initial approval. More than a decade after shortcomings within the U.S. Food & Drug Administration in conducting follow-up safety studies after new drugs are approved were identified, the General Accounting Office (GAO) says the FDA is still dragging its feet by utilizing technology that requires manual entry of data.

    In January of 2016 the General Accounting Office (GAO) of the U.S. finally got around to find out why it has taken the Food & Drug Administration so long to require drug companies to publish all of their follow-up safety data once their drugs gain regulatory approval.

    In an era when the FDA is conceding to pressure to approve new drugs more rapidly, it is not properly monitoring safety of these drugs as it should, says the GAO report. The GAO found that more than half of drug sponsors’ submissions involving about 1400 post-market studies required or requested from the FDA between March 2008 and September 2013 were delayed or overdue.

    The FDA drags its feet since all of the FDA’s tracking data has to be entered manually, which essentially renders the software inadequate. The GAO report suggests the FDA upgrade its technology system. That upgrade is long overdue. [GAO report; Pharmacy Times] What is the FDA hiding?

    A cursory review suggests many existing drugs would have to be withdrawn from the marketplace or be required to publish warnings if adequate safety study data were available. A couple of examples come to mind.

    Alzheimer’s drugs

    Aricept (donepezil) is thought to work in the brain by increasing the levels of an important brain chemical called acetylcholine. This chemical helps a person’s memory to work better.

    In 1997 the Pharmaletter questioned the reported safety and efficacy of Aricept (donepezil), a drug used to improve mental function among patients with moderate dementia. Aricept increases transmission of brain chemicals (acetycholine) by inhibition of the enzyme (acetycholinesterase) that degrades acetycholine. But its effect diminishes over time due to the die off of brain cells (neurons). The Pharmaletter review that the approval of Aricept was based upon data from a single inconclusive trial. [The Pharmaletter 1997]

    In fact, high-dose Aricept was approved over the objection of two FDA reviewers. An appeal to withdraw this drug was issued. [Alliance Human Research Protection]

    In 2006 a study reported 11 deaths among patients taking Aricept and no deaths among patients taking an inactive placebo pill! [WebMD 2006]

    In 2003 a report in the Canadian Medical Association Journal reported that 29% of patients given this class of drugs had to stop taking them due to side effect and that 7 patients must take the drug for 1 to benefit from it; 42 patients must take the drug for 1 patient to experience a marked improvement. [Canadian Medical Association Journal 169: 557, 2003]

    In 1998 the same journal questioned the approval of Aricept based upon inaccessible data that clinicians could not review for themselves. [Canadian Medical Assn. Journal 1998] More than a decade later Canadian researchers were still giving their thumbs down on the use of Aricept. [Canadian Med. Assn. Journal 2013]

    In 2006 researchers in Italy questioned the entire process by which drugs are approved by the FDA and used drugs like Aricept (acetacholinesterase inhibitors) as an example.

    These researchers note that the “gold standard” for FDA approval, a randomized and blinded controlled trial (doctors don’t know which patients were given the drug or an inactive placebo) often address a very narrow patient population and following FDA approval the drug is used on a wider population. These researchers point out the following: [PLoS One 2006]

    Drug companies have invested heavily in developing treatments for Alzheimer disease, and then were actively involved in expanding the market to other forms of dementia…

    Even when the evidence on the efficacy of these drugs is lacking, or inconclusive, the results are often presented in such a way as to create a false perception of efficacy…

    Most of them were not validated for the disease for which the drugs were tested and are not currently used in clinical practice, undermining the translation of these research findings into clinical practice. Moreover, the treatment effect in the trials is usually expressed through the average change from baseline in test scores, without discussing the clinical importance of the usually small effect size observed…

    This class of drugs, which includes Aricept (donepezil), Razedyne (galantamine) and (Exelon (rivastigmine), was licensed in the US in 1996 before the full results of clinical trials were available in medical journals…

    That patients with so-called mild cognitive (mental) decline “may not worsen over time and revert to normal cognitive abilities,” which would skew the results of studies and may make drugs falsely appear to be effective.

    Despite all the lack of data and the concern over safety problems, this class of drugs has become the standard of care for Alzheimer’s disease.

    If families of loved one who experience mental decline insist upon doing something, they might as well reach for a well-tested herbal remedy, huperzine, which not only inhibits the enzyme that degrades acetycholine, but also reduces development of brain plaque (beta amyloid) and iron accumulation in the brain that is a causal factor. [Neurobiology Aging 2014; Frontiers Aging Neuroscience 2014]

    In fact, while Aricept, Razedyne and Exelon target the enzyme that erases acetycholine (acetacholineresterase), a related enzyme (butrylcholinesterase) also breaks down the memory molecule acetycholine. The herbal remedy huperzine does a better job of inhibiting both forms of these breakdown enzymes and appears categorically superior to the FDA-approved drugs. [Journal Alzheimer’s Disease 2014] And huperzine produces fewer side effects than drugs. [Evidence Based Complementary Alternative Medicine 2014]

    The drugs currently employed to address mental decline with advancing age are narrow in their biological scope, whereas huperzine exhibits “multifaceted” protective effects. [Acta Pharmacology Sinica 2012]

    However, the problem of fewer and fewer brain cells over time limits the effectiveness of all of these acetycholinesterase inhibitors. The ideal would be a medicine that enhances brain memory chemicals (acetycholine, dopamine) and inhibits brain cell death. The red wine molecule resveratrol (rez-vair-ah-trol) would be an example. [Toxicology Applied Pharmacology 2015; European Journal Pharmacology 2009]

    Pharmaceutical companies are attempting to produce a drug that inhibits acetycholinesterase but not butyrylcholinesterase in an attempt to reduce the undesirable side effects of these drugs (nausea, vomiting, diarrhea). The specific inhibition of the butyrylcholinesterase is believed to raise the level of acetycholine and improve memory. It appears resveratrol does this. Pharmacologists are attempting to re-engineer resveratrol to make it a drug for this purpose. [Archives Pharmacology 2013] But it is widely available on shelves at vitamin shops.

    As of 2016 there were 292 clinical trials involving Aricept (donezepil) with annual sales exceeding $1 billion worldwide (2013 data). [Evaluate Group]

    Tamiflu (oseltamivir)

    How is it that a flu drug that has been roundly dismissed scientifically is advertised on TV? And no less than on the weakest winter flu season in years.

    Consistent with sudden deaths observed in animal studies, Tamiflu (oseltamivir) was associated with 38 deaths within 12 hours of use. [International Journal Risk Safety Medicine 2011] Another 50 sudden deaths associated with Tamiflu use was reported in 2007. [British Medical Journal 2007]

    Tamilflu is documented as a central nervous system depressant that can induce respiratory suppression and rapid death. [British Medical Journal 2005]

    The Cochrane Database System Review discovered unpublished reports of side effects and deaths which undermined their analysis of Tamiflu. While the Cochrane analysis team found that Tamilflu shortened the duration of the flu by about 21 hours on average, there was no reduction in the number of hospitalizations. Inability to obtain data from the manufacturer hampered the analysis. [Cochrane Database System Review 2012]

    Another analysis published in 2013 concluded “There is no evidence that oseltamivir reduces the likelihood of hospitalization, pneumonia.” [Family Practice 2013]

    While the relative risk for the flu is said to be reduced by 64-92% with Tamilflu, in hard numbers the risk reduction is only 1.2%. [PLoS One 2013]

    The Atlantic published a damning report about Tamiflu which stated that “the only people helped by the proven-to-be-ineffective drug are its manufacturers.” In keeping with the present cozy relationship between government and the drug companies, the US Centers for Disease Control & Prevention used public service announcements to urge people to get Tamiflu upon the first sign of a cold or the flu. [The Atlantic 2013]

    In 2014 Reuters news agency aired a report that said stockpiling of Tamiflu was a waste of money. [Reuters April 10, 2014]

    Ineffective and deadly drugs remain on the market and are even promoted by public health agencies. The FDA is aiding and abetting the use of such drugs by intentionally utilizing manual entry data systems so complete data cannot be analyzed.

    Peter Doshi, watchdog at Johns Hopkins University, recently wrote a scathing article in the British Medical Journal entitled:

    “No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about  institutional responsibility. “

    Doshi’s paper took a drug company to task for its mischaracterization of an antidepressant for adolescents as “generally well tolerated and effective” as published in Study #329. Even an FDA officer called Study #329 “a failed trial,” but it is being used to keep this problematic drug on the market.

    Doshi points out that none of the named authors of this published study wrote it. The paper was written by an outsider hired by a drug company. To make matters worse a demand the paper be retracted was refused by the American Academy of Child & Adolescent Psychiatry. Brown University officials were silent over professional misconduct. [British Medical Journal; Medical Express]

    From top to bottom, from researchers to drug companies, medical journal editors and university officials, the whole lot of them are corrupt in keeping ineffective and unsafe drugs on the market, with innocent children its victims in this case.

    ©2016 Bill Sardi, Knowledge of Health, Inc.

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