Profile: US Food and Drug Administration
US Food and Drug Administration was a participant or observer in the following events:
Vice President Dan Quayle, chairman of the President’s Council on Competitiveness, and Louis Sullivan, secretary of health and human services, announce the FDA’s new policy on the regulation of genetically engineered foods. In the policy statement that is published three days later, the FDA will say it has determined that genetically modified (GM) foods are “substantially equivalent” to conventionally grown foods and therefore will not be subject to any special regulations. The agency justifies its position saying that assessments concerning the safety of food products should be based on the characteristics of the food product and not on the methods used to develop that product. [US Food and Drug Administration, 5/29/1992 ] Specifically addressing the issue of labeling for GM foods, the May 29 statement will read: “The agency is not aware of any information showing that foods derived by these new methods differ from other foods in any meaningful or uniform way, or that, as a class, foods developed by the new techniques present any different or greater safety concern than foods developed by traditional plant breeding. For this reason, the agency does not believe that the method of development of a new plant variety… would… usually be required to be disclosed in labeling for the food.” Labeling would only be required in special cases, the FDA says. For example, if a genetically engineered tomato contains a peanut protein that is a proven allergen, a label will be needed. [US Food and Drug Administration, 5/29/1992, pp. 22991 ] In their statement to the press, Sullivan says that biotechnology promises to develop new food products “that are tastier, more varied, more wholesome, and that can be produced more efficiently.” Quayle’s council played a key role in expediting the development of the policy. [Food and Drug Administration, 5/26/1992] Quayle explains that the policy will ensure the competitiveness of US firms. “The reforms we announce today will speed up and simplify the process of bringing better agricultural products, developed through biotech, to consumers, food processors, and farmers,” he says. “We will ensure that biotech products will receive the same oversight as other products, instead of being hampered by unnecessary regulation.” [New York Times, 1/25/2001]
Merck submits its New Drug Application (NDA 21-042) to the Food and Drug Administration (FDA) for Vioxx, which is intended to treat acute pain in adults, dysmenorrhea and osteoarthritis. The drug is supposed to cause fewer gastrointestinal problems than painkillers currently on the market. The NDA includes results from clinical studies that involved 5,400 subjects. [US Food and Drug Administration, 2005]
The Food and Drug Administration approves Vioxx as a treatment for acute pain, dysmenorrhea, and osteoarthritis in adults, making the drug the second Cox-2 inhibitor available by prescription in the United States. [US Food and Drug Administration, 2005]
The FDA endorses the use of Bayer’s Cipro drug to prevent inhalation anthrax. [Reuters, 7/28/2000] An official recommendation like this is highly unusual for the FDA. A 1997 Pentagon study of anthrax in rhesus monkeys showed that several other drugs were as effective as Cipro. The reason given for only recommending Cipro is the government wants a weapon against anthrax should it come up against a strain resistant to drugs in the penicillin and tetracycline families of antibiotics. [New York Times, 10/21/2001] The pharmaceutical industry spent $177 million on lobbying in 1999 and 2000—more money than any other industry. The FDA has been accused of conflicts of interest with companies including Bayer. [New York Times, 11/4/2001]
Merck informs the FDA about three fatal heart attacks (deaths 18, 19, and 20) that occurred toward the end of VIGOR, the clinical trial for its drug Vioxx that ended last March (see March 2000). These three deaths were initially left out because they had taken place after a February 10 “cut-off” that had been set at the company’s insistence (see Early February 2000) [National Public Radio, 6/8/2006]
The Food and Drug Administration holds an advisory meeting on the VIGOR study, a clinical trial for the drug Vioxx, to assess whether there is a connection between the drug and heart problems. Unlike the VIGOR study published in the New England Journal of Medicine (see November 23, 2000), this group includes heart attacks 18, 19, and 20 (see March 2000) in their analysis. The meeting’s members conclude that there is not enough data to draw a solid conclusion. [US Food and Drug Administration, 3/8/2001; National Public Radio, 6/8/2006] Notwithstanding, they do recommend that physicians be informed that the VIGOR study showed “an excess of cardiovascular events in comparison to naproxen.” [Office of Representative Henry A. Waxman, 5/5/2005, pp. 21 ] On March 7, the agency publishes all of the VIGOR data on its website, as well as its analysis. [US Food and Drug Administration, 3/8/2001]
The FDA informs Aventis that it will not approve the drug Ketek until the company has provided enough information to determine the drug’s safety profile. [Aventis, 6/4/2001] In April, an FDA advisory board recommended additional clinical studies for the drug because of concerns about potential side effects on the heart and liver (see April 26, 2001).
An expert panel convened by the National Science Academy’s Institute of Medicine issues a report recommending a number of changes to how the FDA regulates the drug industry. The proposed changes are unanimously endorsed by the panel, comprised of 15 experts from academic and professional organizations. Some of the recommendations include:
The FDA should implement a moratorium on direct consumer advertising of recently approved classes of drugs until enough aggregate data is available to confirm the drugs’ safety. Packaging for such medications should have a special symbol imprinted on them alerting consumers to the higher risk associated with new medications.
The FDA should be required to reevaluate the safety and effectiveness of drugs at least once every five years after the drug has been approved. The agency’s current system for monitoring drug safety post-approval is far less effective than pre-approval testing. The report notes that there is a history of fierce disagreements between the FDA’s Office of Drug Safety and the agency’s Office of New Drugs.
The FDA should be given new powers to impose fines, injunctions, and withdrawals
when drug companies fail to complete the required safety studies.
The agency should be given the authority to impose a wider range of restrictions on drugs it considers potentially unsafe.
The government should require drug companies to register all clinical trials they sponsor in a government-run database so patients and physicians can review all studies. Currently, only those studies published in medical journals are accessible to the public, and these tend to be the studies that produce the most favorable results for the drug being tested.
Expert advisory panels should not be loaded with industry-connected scientists. Most of the members making up these panels should be free of industry ties. “FDA’s credibility is its most crucial asset, and recent concerns about the independence of advisory committee members… have cast a shadow on the trustworthiness of the scientific advice received by the agency,” the report says. [Institute of Medicine, 9/22/2006; Washington Post, 9/23/2006; New York Times, 9/23/2006]
The New York Times reports that health officials and experts believe numerous other drugs are as effective as the antibiotic Cipro in combating anthrax. “Several generic antibiotics, including doxycycline, a kind of tetracycline, and various penicillins, are also effective against the disease,” and they all are in plentiful supply. [New York Times, 10/23/2001] A 1997 Pentagon study of anthrax in rhesus monkeys showed the other drugs to be equally effective. But Cipro remains the only drug officially recommended by the FDA (see July 27, 2000). [New York Times, 10/21/2001]
After six months of negotiations, Merck and the FDA finally agree on the text for a warning about Vioxx’s cardiovascular side effects that will be added to the drug’s label. The FDA had wanted to include a clear message that Vioxx increases the risk of heart problems since the current version of the label includes no information about such risks. An excerpt from the FDA’s originally proposed text reads: “VIOXX should be used with caution in patients at risk of developing cardiovascular thrombotic events… . The risk of developing myocardial infarction in the VIGOR study was five-fold higher in patients treated with VIOXX 50 mg (0.5 percent) as compared to patients treated with naproxen (0.1 percent).…” The FDA also wanted to include a graph showing that the risk of heart problems increases with continued exposure to the drug. Merck objected to the FDA’s proposals. It insisted that a description of the cardiovascular risks be included in the “Precaution” section of the label, instead of the more severe “Warning” section, as proposed by the FDA. The company also wanted to include results from several disparate clinical studies that had been conducted prior to the drug’s release. These are the same tests that are cited in the “Cardiovascular Card” that Merck sales people show to doctors (see April 28, 2000). But the FDA objected, telling the company that the studies were “trials of different design, size, and duration, using different doses of VIOXX and different comparators” and therefore did not provide useful data for determining the drug’s cardiovascular risk. The FDA eventually concedes to several of Merck’s requests. The final text of the warning is included in the “Precaution” section of the label, as Merck wanted, and does not include the graph that had been requested by the FDA. The text of the cautionary statement is also watered down. The section summarizing the results of the VIGOR study (see March 2000) and two other studies states: “The significance of the cardiovascular findings from these 3 studies (VIGOR and 2 placebo-controlled studies) is unknown.” [Merck, 2001; US Food and Drug Administration, 1/30/2002 ; US Food and Drug Administration, 2005; Office of Representative Henry A. Waxman, 5/5/2005, pp. 16-19 ]
After reviewing results of clinical study 3014 for the antibiotic Ketek, an FDA advisory panel recommends that the drug be approved. [Aventis, 1/9/2003] The panel makes the decision completely unaware that the FDA had discovered problems with the study only a few months before. [ABC, 1/14/2006; Wall Street Journal, 5/1/2006 ] In October, an FDA examiner found that some doctors were reporting fraudulent results. For example, some doctors had failed to record the data properly while others had invited patients into the study who did not meet the necessary qualifications. In one case, several patients who were enrolled in the study were not actually taking the drug (see October 2001-Fall 2002).
Aventis announces that the FDA has again declined to approve the company’s antibiotic drug Ketek, citing the need for additional analyses and information pertaining to Study 3014 (see October 2001-Fall 2002). [Aventis, 1/27/2003]
FDA medical officer Andrew D. Mosholder finds evidence that antidepressant drugs such as Paxil, Zoloft, and Effexor may increase the risk of suicidal thoughts in children. Agency officials praise his work but express a lack of confidence in the data. The FDA takes no action. [Washington Post, 9/24/2004]
Britain’s Department of Health advises doctors treating depressed children to prescribe only Prozac. Other antidepressants like Zoloft, Paxil, Luvox, Effexor, Celexa, and Lexapro should be avoided, it warns, because of a potential link between these drugs and suicidal and hostile behavior. [BBC, 12/10/2003; New York Times, 12/16/2003] The FDA takes no action in the US, and continues to sit on a study by one of its own scientists (see September 2003) that links the drugs to suicidal thoughts in children. [Washington Post, 9/24/2004]
In January 2004, an FDA safety officer determines from analysis of adverse event reports that there may be a link between sudden blindness and the impotency drug Viagra. She recommends that the agency warn doctors and patients about the drug’s possible side effect. FDA staffers generally agree that Viagra’s label needs to be updated with a warning. Two months later, a formal draft safety “consult” on the potential Viagra-blindness link is submitted, followed by a final report in April. The FDA approaches Pfizer, the maker of the drug, but the company “resist[s] the FDA’s initial request to update the Viagra label to include information about the NAION risks,” according to a letter that is later sent to the FDA by Senator Charles E. Grassley. The FDA does not issue a public notice or propose a change to the drug’s label until May 2005 when a study published in the Journal of Neuro-Ophthalmology reports seven cases of men experiencing sudden blindness within 36 hours of taking Viagra. [New York Times, 6/1/2005]
The FDA’s Division of Scientific Investigations says in a memo that Aventis’s clinical study for the drug Ketek, study 3014 (see October 2001-Fall 2002), “uniformly failed to detect data integrity problems when they clearly existed.” The report notes that doctors participating in the study failed to comply with FDA regulations and were found to have engaged in “multiple instances of fraud.” [Wall Street Journal, 5/1/2006 ]
The FDA approves the drug Ketek for treatment of chronic bronchitis, acute bacterial sinusitis, and community-acquired pneumonia in patients age 18 and older. [Aventis, 4/1/2004] The approval decision is made despite evidence that a 2001-2002 clinical trial for the drug, study 3014, was replete with fraudulent data (see October 2001-Fall 2002). The FDA says the approval is based on data submitted in 2000, other studies, and the drug’s safety record overseas where the drug has been in use for several years. [Wall Street Journal, 5/1/2006 ]
At a meeting attended by several officials and managers of the reviewing office of the FDA, David Graham, who recently presented a paper linking Vioxx to the deaths of more than 27,000 Americans, is asked by the director of the FDA reviewing office why he “even thought to study Vioxx and heart attacks because FDA had made its labeling change and nothing more needed to be done,” according to Graham’s later testimony to Congress. Also during the meeting, a senior manager from the Office of Drug Safety refers to Graham’s study as “a scientific rumor.” [US Congress, 11/18/2004 ]
An expert panel convened by the US Food and Drug Administration unanimously agrees that Celebrex, Bextra, and Vioxx “significantly increase the risk of cardiovascular events” such as heart attacks. However the panel does not believe that the risk is so great that these drugs should be banned from the market. (Vioxx was withdrawn from the market voluntarily by its manufacturer in September (see September 30, 2004).) The sales of these drugs should be permitted to continue, but only under strict conditions, the panel says. It also recommends a prohibition on direct marketing to consumers, a patient’s guide for the drug, and a black box warning—the most severe possible—detailing the drug’s cardiovascular side effects. [CNN, 2/18/2005; Washington Times, 2/19/2005] After the vote, the New York Times reveals that 10 of the panel’s 32 members had at one time been paid-consultants to the makers of the drugs in question. In analyzing the votes, the Times discovers that neither Bextra nor Vioxx would have survived the vote if the scientists with connections to the company had not voted. For both Bextra and Vioxx, the industry-connected panelists voted 9 to 1 in favor, while the experts with no ties voted 14 to 8 and 17 to 15 to ban Bextra and Vioxx, respectively. The Times notes in its article that “these votes were deeply important” for the makers of those drugs. After the votes, the shares of Merck and Pfizer increase substantially. In e-mails to the Times, eight of the panelists, responding to questions from the newspaper, say their votes were not influenced by their ties to the companies. Two of the panelists do not respond. One of the panel members, Dr. John Farrar, who has received research support from Pfizer, says, “I think FDA would have a hard time finding people who are good at what they do who never spoke to a pharmaceutical company.” But another panel member, Dr. Curt Furberg, who has no ties, says he was “uncomfortable with the Pfizer-friendly undertone” at the meeting and he felt the industry ties might have contributed to that tone. Furberg adds that it has never been proven that Celebrex, Bextra, or Vioxx offer better pain relief than ibuprofen or more than a dozen other over-the-counter drugs. Daniel E. Troy, the FDA’s former chief counsel and a longtime advocate of drug-maker interests, plays down the importance of the ties, saying that any suggestion that experts’ votes were influenced by industry connections “buys into an overly conspiratorial view of the world.” [New York Times, 2/25/2005]
The Annals of Internal Medicine posts an “early release” version of an article reporting three cases of acute liver failure in previously healthy patients who had taken Ketek. [Los Angeles Times, 6/17/2006] The final version of the article will be published in late March. [Clay et al., 3/21/2006] The FDA, responding to the new data, insists the drug presents no more danger to the liver than other antibiotics. The agency even cites the results of Study 3013, which FDA investigators previously determined relied upon fraudulent data (see October 2001-Fall 2002 and March 25, 2004). [Wall Street Journal, 5/1/2006 ]
In a memo, FDA safety investigators warn that the link between Ketek and liver damage could be more serious than a recent study published in the Annal of Internal Medicine suggested (see January 2006). The memo says there have been 12 cases of liver failure among Ketek patients, including one patient who took only one dose of the medication. Four patients are known to have died, and one had to undergo a liver transplant. They suffered a “profound degree” of liver damage, the memo says. “The rapid tempo and severity of injuries… suggest an acute hypersensitivity-like process.” A review of data on three similar drugs showed far fewer incidents of liver failure, according to the memo. [Los Angeles Times, 6/17/2006]
The Congressional Committee on Government Reform ends a 15-month investigation aimed at assessing how the FDA is fulfilling its regulatory responsibilities. The committee’s report, based on thousands of pages of internal agency enforcement records, concludes that enforcement activity has dropped dramatically under the Bush administration. According to the review, the annual number of FDA warning letters fell 54 percent between 2000 and 2005, from 1,154 to 535, a 15-year low. Additionally, the number of seizures of mislabeled, defective, and dangerous products dropped by 44 percent. According to the investigation, there were at least 138 cases where the FDA ignored recommendations from agency field inspectors to take enforcement actions. [US Congress, 6/26/2006 ; New York Times, 6/27/2006] In letters written to the committee, experts voiced concern that the FDA is becoming less vigilant in its oversight duties. Dr. Jerry Avorn of the Harvard Medical School, wrote that there is “a growing laxity in FDA’s surveillance and enforcement procedures,” a “dangerous decline in regulatory vigilance,” and an “obvious unwillingness to move forward even on claims from its own field offices.” Avorn describes the FDA as “an agency unwilling to exert its regulatory authority in defense of the public’s health.” [Avorn, 6/26/2006 ] Dr. Michael Wilkes of the University of California, Davis, School of Medicine, says the FDA has “systematically ignored District Field Officers and regularly overridden their explicit and well documented concerns about drug safety and public health.” It “seems unable and unwilling to step in to protect the American public,” he adds. [Wilkes, 6/10/2006 ] Another problem identified during the committee’s review of the documents concerns the agency’s record keeping. In response to questions from the committee, officials said the FDA lacks a centralized case tracking system and does not maintain a record of the enforcement recommendations made by its district offices. As a result, the investigation had to rely on the personal recollection of field office employees. [US Congress, 6/26/2006 ]
Libertarian Representative Ron Paul (R-TX), contemplating a run for the 2008 presidential nomination, discusses the many federal programs, agencies, and bureaus he would eliminate if he had the power. He would do away with the CIA, the Federal Reserve, the Food and Drug Administration (FDA), the IRS, and the Department of Education, among others. He would eliminate Social Security, Medicare, and Medicaid. He would abolish the federal income tax (see April 28, 1999). He would zero out federal funding for public education, leaving that to local governments. Paul recently refused to vote for federal funds to aid victims of Hurricane Katrina, explaining that to do so would “rob” other Americans “in order to support the people on the coast.” He routinely votes against federal subsidies for farmers. He supports absolute gun rights, and absolutely opposes abortion, though he thinks regulations supporting or denying abortion should be left up to the states. He wants to repeal federal laws regulating drugs and allow prohibited drugs such as heroin to be sold legally. Paul says the US should withdraw from the United Nations and NATO, and wants the country to stop giving foreign aid to any country for any reason, calling such assistance “foreign welfare.” He even says President Lincoln should never have taken the nation to war to abolish slavery. Referring to the years before the income tax, Paul says: “We had a good run from 1776 to 1913. We didn’t have it; we did pretty well.” As for Social Security, “we didn’t have it until 1935,” Paul says. “I mean, do you read stories about how many people were laying in the streets and dying and didn’t have medical treatment?… Prices were low and the country was productive and families took care of themselves and churches built hospitals and there was no starvation.” Historian Michael Katz describes himself as aghast at Paul’s characterization of American life before Social Security. “Where to begin with this one?” he asks. “The stories just break your heart, the kind of suffering that people endured.… Stories of families that had literally no cash and had to kind of beg to get the most minimal forms of food, who lived in tiny, little rooms that were ill-heated and ill-ventilated, who were sick all the time, who had meager clothing.” Charles Kuffner of the Texas progressive blog Off the Kuff writes, “I can only presume that the Great Depression never occurred in whatever universe Paul inhabits.” [Washington Post, 7/9/2006; Charles Kuffner, 7/10/2006]
Entity Tags: United Nations, US Food and Drug Administration, North Atlantic Treaty Organization, Ron Paul, US Department of Education, US Federal Reserve, Charles Kuffner, Central Intelligence Agency, Internal Revenue Service, Michael Katz
Timeline Tags: Global Economic Crises, Domestic Propaganda, 2008 Elections
In a 93-1 vote, the US Senate passes the Food and Drug Administration Improvement Act of 2007 (H.R.2273), which grants the FDA broad new authority to monitor the safety of drugs after they are approved. It was based in part on the recommendations of a 2001 report by the Institute of Medicine (see September 22, 2001). The institute had been asked by the FDA to examine drug safety after it was revealed that the FDA and drugmaker Merck had permitted the drug Vioxx to stay on the market despite numerous indications that it increased patients’ risk of a heart attack. But the bill that is passed is much weaker than the original version, and ignores some of the institute’s most critical recommendations. A USA Today investigation will find that industry-friendly changes made to the bill were instigated by senators “who raised millions of dollars in campaign donations from pharmaceutical interests.” For example, 49 senators successfully defeated an effort that would have allowed US consumers to import lower-cost drugs from Canada and other industrialized countries. The senators who opposed the provision “received about $5 million from industry executives and political action committees since 2001—nearly three quarters of the industry donations to current members of the Senate,” USA Today found. Another factor contributing to the amendment’s failure was that President Bush said he would veto the bill if it permitted the imports. Also excised from the bill was language that would have give the FDA the authority to ban advertising of high-risk drugs for two years. This was one of the Institute of Medicine’s key recommendations. Senator Pat Roberts (R-Kan) argued that the change would restrict free speech. Drug interests have given Roberts $18,000 so far this year, and $66,000 since 2001. Sen. Judd Gregg (R-NH) was responsible for a change that reduced the agency’s power to require post-market safety studies. He insisted on limiting this authority so that the FDA could only target drugs when there’s evidence of harm. Gregg has received $168,500 from drug industry interests since 2001. The bill’s main sponsors—senators Edward Kennedy, (D-Mass) and Mike Enzi (R-Wyo)—agreed to water down a proposal that would have required all clinical drug studies be made public after meeting with industry officials. The senators agreed to change the language so that only studies submitted to the FDA would be available. Enzi and Kennedy have received $174,000 and $78,000, respectively, from drug interests since 2001. Amendments aimed at reducing industry conflicts of interest on FDA expert advisory panels were also stripped from the bill. One of those amendments would have made it more difficult for scientists to advise the FDA on drug approval applications from a company the scientist had received money from. Another would have required that FDA panels consist of no more than one member with financial ties to the drug industry. The Senate also rejected an amendment to establish an independent FDA office to monitor the safety of drugs after they are released on the market. The office that currently has this authority is the same one that approves new drugs, an arrangement that lawmakers and at least one FDA scientist (see November 18, 2004) believe is a conflict of interest. [WebMD Medical News, 5/9/2007; US Congress, 5/10/2007; USA Today, 5/14/2007]
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