!! History Commons Alert, Exciting News

Context of 'March 2001: Merck Instructs Sales Representatives Not to Discuss Studies Critical of Merck Products'

This is a scalable context timeline. It contains events related to the event March 2001: Merck Instructs Sales Representatives Not to Discuss Studies Critical of Merck Products. You can narrow or broaden the context of this timeline by adjusting the zoom level. The lower the scale, the more relevant the items on average will be, while the higher the scale, the less relevant the items, on average, will be.

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

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

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

A new Merck training manual instructs company sales representives on how to use reprints of medical journal articles in their sales pitches to doctors. The company has divided the reprints into two categories, “approved” and “background.” The “approved” category includes articles that “provide solid evidence as to why [doctors] should prescribe Merck products for their appropriate patients.” Only these articles can be used or cited by Merck sales people. Background articles, on the other hand, cannot be used or even referenced. Doing so would be “a clear violation of Company Policy,” the document says. If a physician has any questions about studies not in the “approved” category, the sales representive should refer the individual to Merck’s medical services department. [Merck, 3/2001 pdf file; Office of Representative Henry A. Waxman, 5/5/2005, pp. 12-13 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

The same day the New York Times publishes an article (see May 22, 2001) raising questions about the safety of Vioxx, Merck sends a bulletin to its sales representatives instructing them in capital letters: “Do not initiate discussions on the results of the… VIGOR study, or any of the recent articles in the press on Vioxx.” The bulletin says that if physicians ask any questions about the cardiovascular safety of Vioxx, sales reps should refer to the “Cardiovascular Card” (a marketing pamphlet on the safety of Vioxx, see April 28, 2000), request that Merck’s “Medical Services” staff fax or Fedex additional information to the doctor, or respond appropriately “in accordance with the obstacle-handling guide.” [Merck, 5/22/2001 pdf file]

Entity Tags: Merck

Timeline Tags: US Health Care

Beginning no later than January 2002, Merck provides its sales staff with detailed information on the prescribing habits of individual doctors, or as they like to call them, “customers.” The data—purchased by Merck from an outside company—allows sales representatives to see how many prescriptions each of their customers writes for any given medication. The sales person can see which customers are prescribing large quantities of Merck drugs and which ones aren’t, indicating to the rep which customers need to be worked on the most. Furthermore, each doctor has a “Merck Potential,” which is a “dollar estimate of each prescriber’s total prescribing volume that can realistically be converted to Merck prescriptions.” Bonuses for reps are based on the overall sales and Merck market shares for their respective sales territories. So the more Merck drugs their customers prescribe, the more money they make. [Merck, 1/2002 pdf file; Office of Representative Henry A. Waxman, 5/5/2005, pp. 13-14 pdf file]

Entity Tags: Merck

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

Ordering 

Time period


Email Updates

Receive weekly email updates summarizing what contributors have added to the History Commons database

 
Donate

Developing and maintaining this site is very labor intensive. If you find it useful, please give us a hand and donate what you can.
Donate Now

Volunteer

If you would like to help us with this effort, please contact us. We need help with programming (Java, JDO, mysql, and xml), design, networking, and publicity. If you want to contribute information to this site, click the register link at the top of the page, and start contributing.
Contact Us

Creative Commons License Except where otherwise noted, the textual content of each timeline is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike