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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 pdf file] 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 pdf file] 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]

Entity Tags: Dan Quayle, Louis Sullivan, US Food and Drug Administration

Timeline Tags: Seeds

Upon learning that the Food and Drug Administration (FDA) has decided not to require special regulation for genetically engineered foods (see May 26, 1992), FDA scientist Dr. Louis J. Pribyl blasts the decision in a memo to his colleagues. “This is the industry’s pet idea, namely that there are no unintended effects that will raise the FDA’s level of concern,” he writes. “But time and time again, there is no data to back up their contention.” Pribyl, one of 17 government scientists who have been working on a policy for genetically engineered food, knows from his own research and studies that the introduction of new genes into a plant’s cell can produce toxins. [New York Times, 1/25/2001]

Entity Tags: Louis J. Pribyl, Food and Drug Administration

Timeline Tags: Seeds

Merck begins the Vioxx Gastrointestinal Outcomes Research (VIGOR) study, involving more than 8,076 subjects. The study is being carried out by a data and safety monitoring board (DSMB) that has been appointed by Merck. The Food and Drug Administration recommends the use of DSMBs but does not require them, nor does it require that the panels are put together by an independent party. Merck appoints Michael Weinblatt of Brigham & Women’s Hospital in Boston to lead the study. Weinblatt’s wife owns $73,000 in Merck stock, which according to doctors consulted by an NPR investigation, is enough to potentially influence Weinblatt’s judgment. Furthermore, during the course of the study, all the panel’s meetings will be attended by Merck employee Deborah Shapiro, who is present even during the panel’s private deliberations. She is also the notetaker for the meetings. [National Public Radio, 6/8/2006] The VIGOR study is the largest clinical trial ever performed for the drug. Half the participants is given Vioxx, while the other half is given naproxen. The study is designed to determine whether Vioxx causes fewer digestive problems than naproxen, an older painkiller. The outcome of this study is important to Merck because Vioxx’s expected characteristic of being gentler on the stomach would be the drug’s only selling point since there is no evidence that it is a better painkiller than other drugs. The FDA currently requires Vioxx to have the same warning about gastrointestinal bleeding that is carried on the Naproxen label. [USA Today, 10/12/2004; CBS News, 4/28/2005; National Public Radio, 6/8/2006]

Entity Tags: Michael Weinblatt, Deborah Shapiro, Merck

Timeline Tags: US Health Care

The VIGOR study’s safety panel has its first meeting. VIGOR, or the Vioxx Gastrointestinal Outcomes Research study, was designed to determine whether Vioxx causes fewer stomach problems than other painkillers on the market (see January 1999). Results as of October 1, 1999 suggest that patients taking Vioxx experience fewer ulcers and less gastrointestinal bleeding than those taking naproxen. [National Public Radio, 6/8/2006]

Entity Tags: Merck

Timeline Tags: US Health Care

At the VIGOR safety panel’s second meeting (see also January 1999 and October 3 or 4, 1999), panel members discuss concerns over the “excess deaths and cardiovascular adverse experiences” observed among patients taking Vioxx. [US Food and Drug Administration, 2/1/2001, pp. 5 pdf file] As of November 1, 1999, 79 patients out of the 4,000 taking the drug have experienced serious heart problems or have died, compared with 41 patients taking naproxen. Minutes of the meeting note that “while the trends are disconcerting, the numbers of events are small.” [National Public Radio, 6/8/2006]

Entity Tags: Merck

Timeline Tags: US Health Care

The VIGOR study’s safety panel meets for a third time and learns that as of December 1, 1999, the number of Vioxx patients who have experienced heart problems or have died is twice as high as those taking naproxen. The panelists are shown a chart with two lines—one showing the number of deaths in the Vioxx group; the other, deaths in the naproxen group. The chart shows that since the sixth week of the study, the line representing the Vioxx group has been going up at an increasingly brisk pace, while the naproxen group’s line rises slower and is relatively linear. [National Public Radio, 6/8/2006] Some members suggest that diverging lines could be “due to cardioprotective effects of Treatment B,” i.e., that naproxen is somehow reducing the risk of heart problems. [US Food and Drug Administration, 2/1/2001, pp. 6 pdf file] The panel’s chairman, Michael Weinblatt, and Merck statistician Deborah Shapiro write a letter to Merck’s Alise Reicin advising that the company develop a plan to study the cardiovascular results before the VIGOR study is completed. When an investigation by NPR learns about this meeting, it asks three experts to comment on the chart and the panel’s decision. All three say that the study should have been called off immediately because the chart clearly showed that the risk of heart problems among those taking Vioxx increased with time. The panel, in a statement to NPR, claims that it did not cancel the study noting that it was not clear to the panelists at the time whether the different rates of heart problems and deaths were a result of Vioxx causing the cardiovascular problems, or naproxen preventing them. But no study has ever proven that naproxen is cardioprotective. [National Public Radio, 6/8/2006; National Public Radio, 6/8/2006]

Entity Tags: Alise Reicin, Michael Weinblatt, Merck, Deborah Shapiro

Timeline Tags: US Health Care

Merck says it does not want to begin developing a plan to analyze the data on the large number of deaths from heart problems that has occurred during a clinical trial for its drug Vioxx (see December 22, 1999 and November 18, 1999). Michael Weinblatt, who is heading the study, sent a request to Merck the month before asking the company to develop such a plan (see December 22, 1999). Merck suggests that they wait and combine the cardiovascular results of this study with the results from other clinical studies for the drug. But Weinblatt is adamant that the company needs to begin analyzing the data immediately, and continues discussing the matter with Merck, which finally agrees to a plan the following month (see Early February 2000). [National Public Radio, 6/8/2006; National Public Radio, 6/8/2006]

Entity Tags: Merck

Timeline Tags: US Health Care

Merck finally agrees to analyze the data on deaths that have occurred during the clinical trials for its drug Vioxx (see December 22, 1999 and November 18, 1999). The analysis was requested by Michael Weinblatt, who is leading the Vioxx study (see December 22, 1999). But Merck says it will only analyze the deaths that take place before February 10, one month before the study ends. Any deaths that occur after this “cut-off” date will not be factored into the analysis. [National Public Radio, 6/8/2006; National Public Radio, 6/8/2006]

Entity Tags: Merck

Timeline Tags: US Health Care

Merck offers Michael Weinblatt, who is heading a clinical trial (see December 22, 1999 and November 18, 1999) for the company’s drug Vioxx, $5,000 a day to sit on a Merck advisory board for 12 days over the next two years. He accepts the offer and signs the contract a few weeks later on March 6. Merck pays him $15,000 up front. [National Public Radio, 6/8/2006; National Public Radio, 6/8/2006]

Entity Tags: Merck, Michael Weinblatt

Timeline Tags: US Health Care

The VIGOR study, a clinical trial for the drug Vioxx, comes to an end (see also January 1999). The goal of the study was to determine whether patients taking Vioxx experienced fewer gastrointestinal problems than subjects taking naproxen, another painkiller. The study’s results back Merck’s claim that Vioxx is gentler on the stomach. But it also seems to confirm the suspicions of some Merck scientists that it causes cardiovascular problems (see November 18, 1999 and December 22, 1999). During the course of the 12-month study, 20 of the patients taking Vioxx died, far more than the number of deaths among the group taking naproxen. [National Public Radio, 6/8/2006; National Public Radio, 6/8/2006] Later analyses of the data from the study find that subjects taking Vioxx were five times more likely to suffer a heart attack. [CBS News, 4/28/2005]

Entity Tags: Merck

Timeline Tags: US Health Care

March 27, 2000: VIGOR Study Results Announced

Merck issues a press release announcing the results of the VIGOR study (see March 2000) and saying that the study showed patients taking Vioxx experienced fewer gastrointestinal problems than patients on naproxen. Merck also says that “significantly fewer thromboembolic events were observed in patients taking naproxen.” Merck asserts that this was due to “naproxen’s ability to block platelet aggregation,” [Merck, 3/27/2000] a theory for which there is no conclusive evidence. [New York Times, 5/22/2001]

Entity Tags: Merck

Timeline Tags: US Health Care

Merck sends all of its sales representatives a “Cardiovascular Card,” a tri-fold pamphlet on the safety of Vioxx, so they “are well prepared to respond to questions about the cardiovascular effects of Vioxx.” Since the announcement (see March 27, 2000) of the VIGOR study results, physicians have been asking the representatives whether Vioxx causes heart problems. The pamphlet contains a table of data appearing to indicate that patients on Vioxx are 11 times less likely to die than patients on standard anti-inflammatory drugs, and 8 times less likely to die from heart attacks and strokes. Another section displays data showing that Vioxx patients are half as likely to suffer heart attacks as patients who receive a placebo. The risk for patients on other anti-inflammatory drugs appears to be identical. [Merck, 4/28/2000 pdf file] But the pamphlet is based on the combined data of several disparate studies, conducted before the drug’s approval. None of the studies were designed to test the cardiovascular safety of the drug. An FDA medical reviewer later tells the staff of a congressional committee that the relevance of those studies to the question of Vioxx’s effects on the heart is “nonexistent.” Furthermore, the reviewer says it would be “ridiculous” and “scientifically inappropriate” to use the pamphlet as evidence of the drug’s safety. [Office of Representative Henry A. Waxman, 5/5/2005, pp. 16-19 pdf file]

Entity Tags: Merck, VIGOR

Timeline Tags: US Health Care

Merck submits the results of the VIGOR clinical trial for its drug Vioxx to the New England Journal of Medicine (NEJM) for publication. The data include only 17 of the 20 deaths that occurred among patients taking Vioxx (see March 2000). [National Public Radio, 6/8/2006] Data concerning the last three deaths were deleted two days before, according to Dr. Gregory Curfman, executive editor of the journal, who does not discover the missing data until December 2004. “When you hover the cursor over the editing changes, the identity of the editor pops up, and it just says ‘Merck,’” Curfman later tells Forbes magazine. [Forbes, 12/8/2005]

Entity Tags: Merck

Timeline Tags: US Health Care

The authors of a paper on VIGOR, a clinical study on the drug Vioxx, submit two sets of corrections to the New England Journal of Science for the manuscript they submitted in May (see May 18, 2000). They do not correct the omission of three fatal heart attacks that occurred toward the end of the study (see March 2000) after a February 10 “cut-off” date (see Early February 2000). [National Public Radio, 6/8/2006]

Timeline Tags: US Health Care

In a memo to Merck scientist Alise Reicin, Merck statistician Deborah Shapiro includes a reference to the three Vioxx deaths that occurred during the last month of the VIGOR study (see March 2000). Those three deaths—numbers 18, 19, and 20—were not included in a paper submitted to the New England Journal of Medicine in which Reicin and Shapiro are listed as authors (see May 18, 2000). [National Public Radio, 6/8/2006]

Entity Tags: Alise Reicin, Deborah Shapiro

Timeline Tags: US Health Care

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]

Entity Tags: US Food and Drug Administration, Merck

Timeline Tags: US Health Care

The New England Journal of Medicine publishes the VIGOR paper (see May 18, 2000) summarizing the results of a clinical trial for the drug Vioxx. The paper’s main conclusion is that patients taking the drug experienced fewer gastrointestinal complications than patients taking naproxen, another painkiller. This conclusion is important to Merck, the maker of the drug, because this is Vioxx’s only selling point. There is no evidence that Vioxx is a more effective painkiller than any other drug available on the market. But the paper’s section on “General Safety” is misleading because the authors leave out the deaths of three Vioxx patients (see March 2000). The authors were aware of the fatal heart attacks and had at least two opportunities to correct these omissions (see July 2000-November 2000). Notwithstanding their knowledge of these deaths, the authors say there is no causal relationship between Vioxx and heart problems. [Bombardier et al., 2000; National Public Radio, 6/8/2006] When the Journal learns about the missing deaths, executive editor Dr. Gregory Curfman, demands a correction. He tells Forbes magazine, “I was somewhere between surprised and stunned. They allowed us to publish an article that was just incomplete and inaccurate in some respects and was misleading and may have contributed to the detriment to the public health.” [Forbes, 12/8/2005]

Timeline Tags: US Health Care

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 pdf file] 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]

Entity Tags: US Food and Drug Administration

Timeline Tags: US Health Care

Fearing increased public concern over the safety of Vioxx, Merck sends its sales representatives a bulletin instructing them in all capital letters: “Do not initiate discussions on the FDA Arthritis Advisory Committee… or the results of the… VIGOR study.” The previous day, an FDA panel (see February 8, 2001) reviewed the results of the VIGOR study and said physicians need to be informed that Vioxx appears to cause “an excess of cardiovascular events in comparison to naproxen.” The Merck bulletin provides a list of responses that its representatives are authorized to use in addressing physicians’ concerns. It emphasizes that these are the only responses they are allowed to use. If doctors ask about Vioxx’s effects on the heart, sales persons should say, “Because the study is not in the label, I cannot discuss the study with you.” However, as a report by Henry A. Waxman notes, drug company representatives are permitted by FDA regulations to discuss safety concerns even when those concerns are not on the label. The sales persons are also advised to tell physicians to submit their questions in writing to Merck’s medical services department. Merck says reps can also show the physicians the Cardiovascular Card, a pamphlet consisting of data that appears to show that Vioxx is safe (see April 28, 2000). The bulletin indicates that sales reps are not supposed to leave the pamphlet with the doctor. [Merck, 2/9/2001 pdf file; Office of Representative Henry A. Waxman, 5/5/2005, pp. 22 pdf file]

Entity Tags: Merck

Timeline Tags: US Health Care

In a 7 to 3 vote, an FDA advisory panel recommends approving the antibiotic Ketek, also known as telithromycin, for use in treating streptococcus pneumonia. But the panel does not recommend approving it for use against acute chronic bronchitis, sinusitis, or penicillin-resistant or erythromycin-resistant strep. The panel also recommends conducting additional clinical trials to “see if hints of concern… are real or not” about the drug’s potential side affects on the heart and liver. [Associated Press, 4/26/2001]

Timeline Tags: US Health Care

The New York Times reports the results of the VIGOR study (see March 2000), which showed that Vioxx, marketed by Merck, increases the risk of heart attacks four-fold (later studies increase this to five-fold). The Times also reports Merck’s interpretation of the results—that the different number of heart attacks suffered by patients taking Vioxx compared to those using naproxen was due to the heart-protective properties of naproxen. But no studies have been done showing that naproxen prevents heart attacks, says Dr. Maria Lourdes Villalba, an FDA scientist who was interviewed by the newspaper. Another scientist, Dr. M. Michael Wolfe, chief of the gastroenterology section at the Boston University School of Medicine, says people need to know about these risks. “The marketing of these drugs is unbelievable. I’m sure there are many people out there who are taking these drugs that should not be,” he says. Another concern noted is that the very same people who are likely to take the drug—elderly people with arthritis—are the ones with the highest risk of having heart problems. [New York Times, 5/22/2001]

Entity Tags: VIGOR, Merck

Timeline Tags: US Health Care

Merck issues a press release titled “Merck Confirms Favorable Cardiovascular Safety Profile of Vioxx” asserting that there is no evidence that patients taking the prescribed dosage levels of Vioxx have an increased risk of having heart problems. It says that the higher number of heart troubles experienced by patients taking Vioxx compared to naproxen during the VIGOR study (see March 2000) was likely because naproxen has similar properties to aspirin, which is known to prevent heart attacks. [Merck, 5/22/2001] The FDA later issues a warning to Merck calling this press release “simply incomprehensible, given the rate of MI and serious cardiovascular events compared to naproxen” (see September 17, 2001). [US Food and Drug Administration, 9/17/2001, pp. 1-2 pdf file]

Entity Tags: Merck

Timeline Tags: US Health Care

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).

Entity Tags: Aventis, US Food and Drug Administration

Timeline Tags: US Health Care

An new analysis of data from the VIGOR study (a clinical trial for Vioxx, see January 1999) along with data from a clinical trial of the drug Celebrex, and two smaller studies, raises concerns that COX-2 inhibitors may cause cardiovascular events. The study, published in the Journal of the American Medical Association, concludes that “it is mandatory to conduct a trial specifically assessing cardiovascular risk and benefit of these agents.” The authors are cardiologists Debabrata Mukherjee, Steven Nissen, and Eric Topol. [Mukherjee, Nissen, and Topol, 2001; National Public Radio, 6/8/2006]

Entity Tags: Steven Nissen, Eric Topol, Debabrata Mukherjee

Timeline Tags: US Health Care

The Food and Drug Administration faxes a warning letter to Raymond Gilmartin, the CEO of Merck, accusing the company of conducting a deceptive promotional campaign for its drug Vioxx. The eight-page letter, referring mostly to events that took place between June 2000 and June 2001, states: “You have engaged in a promotional campaign for Vioxx that minimizes the potentially serious cardiovascular findings that were observed in the VIOXX Gastrointestinal Outcomes Research (VIGOR) study (see March 2000), and thus, misrepresents the safety profile for VIOXX. Specifically, your promotional campaign discounts the fact that in the VIGOR study, patients on VIOXX were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator non-steroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen).… You assert that Vioxx does not increase the risk of MIs and that the VIGOR finding is consistent with naproxen’s ability to block platelet aggregation like aspirin. That is a possible explanation, but you fail to disclose that your explanation is hypothetical, has not been demonstrated by substantial evidence, and that there is another reasonable explanation, that Vioxx may have pro-thrombotic properties [i.e., cause heart attacks]. You have also engaged in promotional activities that minimize the Vioxx/Coumadin (warfarin) drug interaction, omit important risk information, make unsubstantiated superiority claims against other NSAIDS, and promote Vioxx for unapproved uses and an unapproved dosing regimen.… Your minimizing these potential risks and misrepresenting the safety profile for Vioxx raise significant public health and safety concerns.” The letter also warns the company about a May 2001 press release (see May 22, 2001), which claimed the drug has a “favorable cardiovascular safety profile.” [US Food and Drug Administration, 9/17/2001, pp. 1-2 pdf file]

Entity Tags: Raymond Gilmartin, Merck

Timeline Tags: US Health Care

Aventis contracts Pharmaceutical Product Development, Inc. to do a clinical trial for Ketek, an antibiotic designed to treat respiratory infections. The trial, named “Study 3014,” is being done because of FDA concerns (see Early June 2001) about possible links to heart and liver problems. The company pays doctors $400 for each patient they enroll in the study. Some of the doctors—a bit overzealous in recruiting patients—forge signatures, sign up family members, and invite patients into the study who do not have infections. There are also problems with the way some of the doctors collect and record their data. One doctor, who enrolls 251 patients, does not follow the study’s instructions and fails to report adverse drug reactions. Another physician, Dr. Maria Anne Kirkman-Campbell, who runs a weight-loss clinic, signs up 407 patients—but only 10 percent of them actually take the drug. These problems are discovered by FDA inspectors in fall 2002. [ABC, 1/14/2006; Wall Street Journal, 5/1/2006 pdf file]

Entity Tags: Pharmaceutical Product Development, Inc., Aventis, Maria Anne Kirkman-Campbell

Timeline Tags: US Health Care

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 pdf file; US Food and Drug Administration, 2005; Office of Representative Henry A. Waxman, 5/5/2005, pp. 16-19 pdf file]

Entity Tags: US Food and Drug Administration, VIGOR, Merck

Timeline Tags: US Health Care

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 pdf file] 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).

Entity Tags: US Food and Drug Administration

Timeline Tags: US Health Care

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]

Entity Tags: Aventis, US Food and Drug Administration

Timeline Tags: US Health Care

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 pdf file]

Entity Tags: Aventis, US Food and Drug Administration

Timeline Tags: US Health Care

April 1, 2004: FDA Approves Ketek

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 pdf file]

Entity Tags: Aventis, US Food and Drug Administration

Timeline Tags: US Health Care

The Food and Drug administration approves Vioxx for children who are over the age of 2 and have symptoms of rheumatoid arthritis. [US Food and Drug Administration, 6/1/2005 pdf file] The approval is announced on September 8. [United Press International, 9/8/2004; Medical News Today, 9/9/2004]

Entity Tags: US Food and Drug Administration

Timeline Tags: US Health Care

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 pdf file]

Entity Tags: US Food and Drug Administration

Timeline Tags: US Health Care

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]

Entity Tags: US Food and Drug Administration

Timeline Tags: US Health Care

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