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Context of 'May 6, 2004 and After: FDA Refuses to Allow ‘Morning-After’ Birth Control Pill to be Sold without Prescription'

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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

In Geneva, at the 1998 World Health Assembly, delegates from the US State Department and the Food and Drug Administration (FDA ) threaten to withdraw funding for the World Health Organization (WHO) when members propose including a provision in its resolution on the Revised Drug Strategy that would urge countries “to ensure that public-health interests rather than commercial interests have ‘primacy’ in pharmaceutical and health policies.” As a result of the United States’ opposition, the statement is not adopted. The US also opposes a proposal to give the WHO a role in monitoring international trade agreements. [Consumer Project on Technology, 5/13/1998; Consumer Project on Technology, 10/16/1998; Wilson et al., 11/27/1999]

Entity Tags: World Health Organization, Clinton administration

Timeline Tags: Neoliberalism and Globalization

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]

Entity Tags: US Food and Drug Administration, Merck

Timeline Tags: US Health Care

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

May 20, 1999: Vioxx Approved by FDA

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]

Entity Tags: US Food and Drug Administration

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

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

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

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:
bullet 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.
bullet 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.
bullet The FDA should be given new powers to impose fines, injunctions, and withdrawals when drug companies fail to complete the required safety studies.
bullet The agency should be given the authority to impose a wider range of restrictions on drugs it considers potentially unsafe.
bullet 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.
bullet 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]

Entity Tags: US Food and Drug Administration, Institute of Medicine

Timeline Tags: US Health Care

The Bush administration decides to drop its plan to nominate Dr. Alastair J. J. Wood as commissioner of the Food and Drug Administration. An article recently posted on the conservative National Review Online’s website warned that Wood is not friendly to industry interests. “The people I know in clinical pharmacology, in the research trenches, went berserk when they heard about Wood,” wrote Robert Goldberg, a senior fellow at New York’s Manhattan Institute, a free-market think tank. Goldberg said the doctor is overly obsessed with drug safety and asserts, falsely, that Wood is “a buddy of Senator Ted Kennedy.” The attack on Wood was continued in the editorial pages of the Wall Street Journal six days later in a piece titled “It’s Not Ted’s FDA.” Shortly after the publication of these articles, the White House calls Wood to inform him that the administration is no longer considering his nomination for commissioner, a post that has been vacant for more than a year. Republican Senator Bill Frist—the person who had recommended Wood’s nomination—tells the Boston Globe that the White House was concerned that Wood “put too much emphasis on the safety.” Wood’s track record was evidence that he might take an aggressive approach to regulating drugs. He previously called for an independent board to investigate potentially deadly drugs. The current policy is to allow the drug companies to do their own studies on adverse drug reactions and then provide these results to the FDA. Wood has also said that he believes the current FDA regulatory process has an inherent conflict of interest because the same department that approves drugs is also in charge of reviewing the safety of those drugs post-approval, a criticism that is shared by at least one FDA insider (see November 18, 2004). Furthermore, in May 2001, Wood supported making three allergy prescription drugs—Pfizer’s Zyrtec, Schering-Plough’s Claritin, and Aventis’s Allegra—available over-the-counter (OTC). The companies were opposed to the idea because OTC drugs are often sold at lower prices and are not typically covered by insurance. During a panel discussion on the issue, Wood had noted, “What we have today is an unseemly parade of people trying to protect their own financial interests.” [Boston Globe, 5/27/2002]

Entity Tags: Robert Goldberg, Bush administration (43), Alastair J. J. Wood

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

The Food and Drug Administration (FDA) announces that it will not permit pharmacies to sell the emergency contraception drug “Plan B” without a prescription. The drug is a “morning-after” birth-control drug that prevents fertilization and the implantation of the embryo. The agency explains to the manufacturer of the drug, Barr Pharmaceuticals, that the government is worried about the possibility that teenaged girls might not understand how to correctly use the drug without a doctor’s advice. The FDA’s decision is in direct contradiction of a federal advisory panel’s 23-4 decision to recommend approving the drug for over-the-counter sales, including to teenagers, without a doctor’s approval. The FDA’s staff recommended that the agency follow the panel’s recommendation. In 2007, author and reporter Charlie Savage will write, “Normally, agencies such as the FDA base their decisions on the information provided by their expert advisory panels—but, strangely, not this time.” A spokesman for the presidential campaign of John Kerry (D-MA) says: “By overruling a recommendation by an independent FDA review board, the White House is putting its own political interests ahead of sound medical policies that have broad support. This White House is more interested in appealing to its electoral base than it is in protecting women’s health.” James Trussell, director of the office of population research at Princeton University and a member of the advisory board, says, “The White House has now taken over the FDA.” Numerous women’s groups accuse the FDA’s political appointees of overruling the experts in order to please social conservatives who believe that the “Plan B” drug encourages promiscuity and is a form of abortion. In the following months, a lawsuit will be filed to have the FDA’s decision overturned (see January 21, 2005 and After). [New York Times, 3/7/2004; Savage, 2007, pp. 300-301]

Entity Tags: Charlie Savage, Barr Pharmaceuticals, Bush administration (43), James Trussell, John Kerry, Food and Drug Administration

Timeline Tags: US Health Care, Civil Liberties

FDA scientist David Graham has analyzed data on 1.4 million Kaiser Permanente patients who took Vioxx, Celebrex, or another non-steroidal anti-inflammatory drug (NSDAID) between 1999 and 2003. Based on his findings, Graham believes there have been more than 27,000 heart attacks and sudden cardiac deaths in the US that would not have occurred had those patients been prescribed Celebrex instead of Vioxx. [Washington Post, 10/8/2004] When the FDA reviews a summary of his study, which Graham will present in France on August 25 (see August 25, 2004), his conclusion triggers “an explosive response from the Office of New Drugs.” Graham later tells Congress, “I was pressured to change my conclusions and recommendations, and basically threatened that if I did not change them, I would not be permitted to present the paper at the conference. One Drug Safety manager recommended that I should be barred from presenting the poster at the meeting.” [US Congress, 11/18/2004 pdf file] In an August 12 e-mail, John Jenkins, director of the Office of New Drugs, suggests “watering down” the report’s conclusions because the FDA is “not contemplating” a warning against high-doses of Vioxx. In response, Graham says, “I’ve gone about as far as I can without compromising my deeply-held conclusions about this safety question.” In another e-mail, a different top official expresses concern about how the report might impact Merck. The person writes that the company should be warned beforehand “so they can be prepared for [the] extensive media attention that this will likely provoke.” [Wall Street Journal, 10/8/2004; Washington Post, 10/8/2004]

Entity Tags: John Jenkins, David Graham

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

David Graham, associate science director for the FDA’s Office of Drug Safety, presents the findings of a study on Vioxx in a poster exhibit at an international medical conference in Bordeaux, France. According to Graham’s research, thousands of Americans have died from taking the drug. In his study, he analyzed data on 1.4 million Kaiser Permanente patients that took Vioxx, Celebrex, or another non-steroidal anti-inflammatory drug (NSDAID) between 1999 and 2003. According to Graham’s analysis of the data, the risk of having a heart attack or dying from heart problems is 3.2 times higher for Vioxx patients than people who do not use painkillers, and twice as high for those using Celebrex. Based on these figures, Graham estimates that more than 27,000 Americans have had heart attacks or died from sudden cardiac deaths as a result of taking Vioxx instead of Celebrex. In response to Graham’s study, Merck, the maker of Vioxx, issues a statement insisting that its drug is safe. Alise Reicin, vice president of clinical research at Merck, claims that numerous studies comparing the drug to a dummy pill found “no difference in the risk of having a serious cardiovascular event.” FDA spokeswoman Laura Alvey says the FDA has no plans to ban the drug. “Removing the drug from the market is not on the table,” she says. [Associated Press, 8/26/2004] Prior to the event, FDA officials had pressured him to water down his conclusions (see Mid-August 2004).

Entity Tags: Laura Alvey, Alise Reicin, David Graham, Merck

Timeline Tags: US Health Care

Merck voluntarily withdraws Vioxx from the market after a long term colon-polyp prevention study, called APPROVe, appears to show that the drug doubles the risk of heart attacks or strokes when taken for 18 months or longer. [Merck, 9/30/2004 pdf file] Acting FDA Commissioner Dr. Lester M. Crawford praises Merck for “promptly reporting these finding” to the FDA. [US Food and Drug Administration, 9/30/2004] An estimated 107 million people have used Vioxx since it was approved in 1998. A paper by FDA scientist David Graham, published in the British medical journal Lancet, will later suggest that 88,000-140,000 Americans may have suffered serious coronary heart disease as a result of taking the drug. (see January 25, 2005)

Entity Tags: Lester M. Crawford

Timeline Tags: US Health Care

David Graham, associate science director for the FDA’s Office of Drug Safety, appears before the Senate Committee on Finance to testify on the agency’s ability to protect the American public from harmful drugs. Graham, a twenty-year veteran of the agency, tells the committee that “the FDA, as currently configured, is incapable of protecting America against another Vioxx. We are virtually defenseless.” Graham was an early critic of Vioxx, a painkiller that was recalled in September (see September 30, 2004) because of its link to heart problems. Graham recounts how in August (see Mid-August 2004), the FDA tried to suppress a study he led which found that “nearly 28,000 excess cases of heart attack or sudden cardiac death were caused by Vioxx.” He says the study’s findings were “extremely conservative” and that “a more realistic and likely… estimate ranges from 88,000 to 139,000 Americans” of which “30-40 percent [or 26,400-55,600] probably died.” He notes that this figure is the “rough equivalent of 500 to 900 aircraft dropping from the sky… [or] 2-4 aircraft every week, week in and week out, for the past 5 years.” [US Congress, 11/18/2004 pdf file] The remainder of Graham’s testimony focuses on problems within the FDA’s Office of Drug Safety (ODS). He makes the following points:
bullet The Office of New Drugs (ONS), which approves all new drugs, is the same division that is responsible for taking regulatory action against those drugs after they have been released on the market. This is an inherent conflict of interest, he notes, because when a problem arises, recognizing it would require the ONS to acknowledge that it had made a mistake. Instead, the office’s “immediate reaction [to a problem] is almost always one of denial, rejection, and heat.” [US Congress, 11/18/2004 pdf file]
bullet The Office of Drug Safety (ODS) is subordinate to the Office of New Drugs, and consequently the management of the former sees its mission as pleasing the latter. [US Congress, 11/18/2004 pdf file]
bullet The culture of the FDA’s Center for Drug Evaluation and Research (CDER) “views the pharmaceutical industry it is supposed to regulate as its client, over-values the benefits of the drugs it approves and seriously under-values, disregards, and disrespects drug safety.” [US Congress, 11/18/2004 pdf file]
bullet The Office of New Drugs refuses to take regulatory action on any drug unless it can be shown with 95 percent or greater certainty that it is unsafe. However “to demonstrate a safety problem with 95 percent certainty, extremely large studies are often needed… [and] those large studies cannot be done.” Graham suggests the 95 percent rule makes as much sense as a person with a 100-chamber pistol loaded with 90 bullets saying that the gun is safe. “Because there is only a 90 percent chance that a bullet will fire when I pull the trigger, CDER would conclude that the gun is not loaded and that the drug is safe.” [US Congress, 11/18/2004 pdf file]

Entity Tags: David Graham

Timeline Tags: US Health Care

The Center for Reproductive Rights (CRR) files a lawsuit against the Food and Drug Administration (FDA) asking that the courts reverse a recent FDA decision not to allow the so-called “morning-after” birth-control drug “Plan B” to be sold without a prescription (see May 6, 2004 and After). The CRR says the FDA’s decision was made based on politics and not science. CCR president Nancy Northrup will say that the FDA’s decision “broke its own rules, held Plan B to a higher standard than other over-the-counter drugs, and [as a result,] women have suffered the consequences.” Testimony and depositions gathered indicate that the FDA indeed placed politics over science in its decision. One scientist says that a deputy FDA commissioner told her that the over-the-counter (OTC) application for Plan B had to be rejected “to appease the administration’s constituents,” and that it could later be quietly approved for adults only (see March 4, 2008). Another scientist testifies that he learned before the 2004 decision was issued that then-FDA commissioner Mark McClellan—the brother of White House press secretary Scott McClellan—had already decided to disapprove the drug even before the FDA’s advisory panel had completed its analysis. However, McClellan will deny the accusation. [Center for Reproductive Rights, 11/14/2005; Savage, 2007, pp. 301-302]

Entity Tags: Mark McClellan, Center for Reproductive Rights, Nancy Northrup, Food and Drug Administration, Scott McClellan

Timeline Tags: US Health Care, Civil Liberties

The British medical journal Lancet publishes a paper by FDA scientist David Graham suggesting that tens of thousands of Americans probably died from taking Vioxx, a painkiller that was recalled in September (see September 30, 2004). His study looked at data on 1.4 million Kaiser Permanente patients that took Vioxx, Celebrex, or another non-steroidal anti-inflammatory drug (NSDAID) between 1999 and 2003. The data showed that the risk of having a heart attack or dying from heart problems was 1.6 times higher for patients taking standard-dose Vioxx compared with those using Celebrex. The risk was 3.6 times higher for those on high doses. Graham notes that Vioxx’s potential impact on the patient population was likely severe. Using the risk factors from Merck-sponsored randomized clinical trials, and extrapolating these to the estimated 106.7 million Vioxx patients, Graham says that the drug may have caused cardiovascular problems for 88,000-140,000 Americans. It is estimated that 44 percent of acute myocardial infarction’s are fatal. [Graham et al., 2005 pdf file; London Times, 1/25/2005] In November, Graham told Congress that senior managers at the FDA’s Office of Drug Safety had delayed giving Graham permission to publish this study, even after it had been accepted by Lancet. [US Congress, 11/18/2004 pdf file]

Entity Tags: David Graham

Timeline Tags: US Health Care

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]

Entity Tags: Daniel E. Troy, John Farrar, Curt Furberg, US Food and Drug Administration

Timeline Tags: US Health Care

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]

Entity Tags: George W. Bush, Edward M. (“Ted”) Kennedy, Judd Gregg, Mike Enzi, US Food and Drug Administration, Pat Roberts

Timeline Tags: US Health Care

A federal judge dismisses a lawsuit seeking to halt sales of the so-called “morning-after” birth control pill, the only such drug available in the US without a prescription. In 2006, the FDA reversed its 2004 decision not to allow the drug to be sold over the counter (see May 6, 2004 and After) to anyone 18 years of age or older. The suit was brought by the Association of American Physicians and Surgeons and a number of anti-abortion and social conservative groups. The US District Court in the District of Columbia finds that the plaintiffs failed “to identify a single individual who has been harmed by Plan B’s OTC [over-the-counter] availability.” The ruling is widely considered to be a victory for advocates of reproductive rights. “They still don’t have any evidence in terms of why they think it is harmful,” says Janet Crepps of the Center for Reproductive Rights (CRR). “This is the right decision for women.” A lawsuit filed by the CRR to force OTC sales of the drug to girls under 18 is still pending (see April 22, 2009). [Reuters, 3/4/2008]

Entity Tags: Association of American Physicians and Surgeons, Food and Drug Administration, Janet Crepps, Center for Reproductive Rights

Timeline Tags: US Health Care, Civil Liberties

The Food and Drug Administration (FDA) announces that, in line with a judge’s recent ruling, it will approve the sale of the so-called “morning-after” emergency contraception pill to 17-year olds without a doctor’s prescription. A judge recently ruled in favor of the Center for Reproductive Rights (CRR) in a lawsuit against the FDA (see January 21, 2005 and After). Under the Bush administration, the FDA ruled that the pill, called “Plan B,” could not be sold without a prescription (see May 6, 2004 and After), a decision partially reversed in 2006. Conservative groups say the decision will make it more difficult for parents to supervise their teens; women’s rights groups say the decision strengthens the rights of women. District Judge Edward Korman ruled that the FDA’s political appointees placed politics over science in its decision to restrict over-the-counter (OTC) sales of the drug; he wrote that evidence showed White House officials pressured the FDA to reject the drug’s OTC sales. His ruling orders the FDA to allow OTC sales to 17-year olds, and to evaluate whether all age restrictions should be lifted. CRR’s Nancy Northrup says, “It’s a good indication that the agency will move expeditiously to ensure its policy on Plan B is based solely on science.” Wendy Wright of the conservative action group Concerned Women for America says, “Parents should be furious at the FDA’s complete disregard of parental rights and the safety of minors.” In 2008, a judge ruled that conservative groups had failed to prove that the drug posed a risk to anyone (see March 4, 2008). Former FDA official Susan Wood, who resigned in 2005 over the issue, says the battle over Plan B came to symbolize just how politicized the agency became under President Bush. “The FDA got caught up in a saga, it got caught up in a drama,” she says. “This issue served as a clear example of the agency being taken off track, and it highlighted the problems FDA was facing in many other areas.” [Associated Press, 4/22/2009; Washington Post, 4/23/2009] “We need to have a very strong and science-based agency, and this is one of those steps that will help strengthen it,” Wood says. [USA Today, 3/23/2009]

Entity Tags: George W. Bush, Bush administration (43), Center for Reproductive Rights, Food and Drug Administration, Susan Wood, Wendy Wright, Nancy Northrup, Edward Korman

Timeline Tags: US Health Care, Civil Liberties

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