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US Health Care System

Clinical drug studies

Project: US Health Care System
Open-Content project managed by kuhan, mtuck

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During this period, pharmaceutical companies begin hiring fewer and fewer universities to perform the clinical research studies for their drugs, contracting instead private research firms or conducting the studies themselves. In the early 1990s, roughly 75 percent of drug companies’ clinical research budgets went to universities. By 2000, this figure drops to only 34 percent. [New York Times, 11/22/2002]

Category Tags: Clinical drug studies

A Merck official writes a memo on the question of whether the company should conduct a trial to demonstrate that Vioxx is gentler on the stomach than other painkillers. The memo notes that such a study would likely show that “there is a substantial chance that significantly higher rates” of cardiovascular problems will occur among the patients taking Vioxx. [Wall Street Journal, 11/1/2004; CBS News, 4/28/2005]

Entity Tags: Merck

Category Tags: Clinical drug studies, Disregard for Public Safety, Vioxx

A Merck clinical trial of Vioxx conducted on 978 patients suggests the drug substantially increases the risk of serious cardiovascular events, including heart attack and stroke. Patients who take Vioxx are six times as likely to suffer heart problems than patients taking an alternative painkiller or a placebo. The study, named Study 090, is never published. Merck later says this is because the sample size was not large enough to provide statistically significant data. [US Food and Drug Administration, 2/1/2001, pp. 31-34 pdf file; Topol, 2004; CBS News, 4/28/2005]

Entity Tags: Merck

Category Tags: Clinical drug studies, Manipulation of data, Vioxx

Omnicom, one of the world’s largest advertising firms, pays $20 million for part-ownership of Scirex, a research firm that conducts clinical studies on drugs to determine their effectiveness and safety. Thomas L. Harrison, a top executive of the company, says he expects Scirex’s studies to provide positive results for its clients in the drug industry. “Our goal is to help ensure that all clinical studies and each patient accrued into a study can be assessed to support the NDA submission.” [New York Times, 11/22/2002]

Entity Tags: Omnicom, Scirex, Thomas L. Harrison

Category Tags: Clinical drug studies

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

Category Tags: Clinical drug studies, Vioxx

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

Category Tags: Clinical drug studies, Disregard for Public Safety, Vioxx

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

Category Tags: Clinical drug studies, Disregard for Public Safety, Vioxx

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

Category Tags: Clinical drug studies, Disregard for Public Safety, Vioxx

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

Category Tags: Clinical drug studies, Manipulation of data, Vioxx

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

Category Tags: Clinical drug studies, Vioxx

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

Category Tags: Clinical drug studies, Vioxx

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

Category Tags: Clinical drug studies, FDA advisory panels, Studies-Academic

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

Category Tags: Clinical drug studies, Ketek

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

Category Tags: Clinical drug studies

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

Category Tags: Clinical drug studies, FDA advisory panels, Defense of corporate interests, Vioxx

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