Bextra, Celebrex maker Pfizer again in trouble

Pfizer, the maker of now recalled Bextra (along with its sister drug Celebrex that carries a strong black box warning), which also markets the erectile dysfunction drug Viagra, is being investigated by the FDA for possible linkage of Viagra and blindness.

The FDA approved Viagra on March 27, 1998. Viagra is the first oral pill to treat impotence, a dysfunction that affects millions of men in the United States. The other drug that competes with Viagra is Cialis. Both drugs have been prescribed to millions of Americans and are now available all over the world.

The debate is about NAION (non-arteritic anterior ischemic optic neuropathy), which causes sudden vision loss when blood flow to the optic nerve is blocked. Optic nerve plays a critical role in vision. NAION is considered to be one of the most common causes of sudden vision loss in older Americans. Risk factors include diabetes and heart disease, which also happen to be the leading causes of impotence.

Pfizer is yet to release a statement for the press, but that is not surprising since it generally stands by the safety of its drugs even if scientific research shows contradictory data. For instance, Pfizer continues to claim that Bextra is a safe drug and is working to bring Bextra on the market. It is also fighting hard with the FDA to not put a black box warning on Celebrex.

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Vioxx recall lawsuits to exceed 100,000

It appears that personal injury lawsuits against Merck, the maker of now recalled Vioxx, may exceed 100,000. This estimate was announced by the U.S. District Court Judge Eldon Fallon, who is handling Vioxx litigation. While the number may appear to be huge, it is something that most analysts had expected considering that as many as 140,000 Americans have been injured, and of which, as many as 50,000 may be dead, according to FDA estimates. (Related link: Pfizer defends Bextra and calls it safe)

There is still no good number regarding Merck's Vioxx liabilities, since a lot depends on what the juries think of Merck's aggressive marketing tactics and how convinced they are of Merck's position that Vioxx had nothing to do with deaths and injuries. A number often cited for Merck's legal liability is $18 billion though some estimates put the total settlement amounts could reach $55 billion. Merck is reported to have used projects code-named "Dodge Ball Vioxx," "Offense" and "XXceleration" to market Vioxx to doctors who did not ask the right questions and Americans who simply trusted their doctors and Merck to do the right thing. (Related article: Merck hid Vioxx dangers prior to recall)

The Vioxx cases are gradually making their way through the American court system. No case has been brought to trial yet due to delays. For instance, one of the first cases to be tried was that of Cheryl Rogers, widow of Brad Rogers, who is suing for the death of her husband after taking Vioxx. Since her attorneys are reviewing approximately 5 million documents of evidence against Merck, they have asked that the trial be postponed till July, 2005.

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Aleve is an option after Vioxx, Bextra recall

Recent controversy about the safety of pain medications for arthritis has left patients and health care professionals alike confused about which medications are safe to use. In fact, a recent survey by the Boston-based Rippe Lifestyle Institute indicated that many people with arthritis are suffering unnecessarily because they have stopped or reduced their use of pain relievers due to confusion about which drugs are considered safe. (Related article: Recall of Vioxx and Bextra makes it important to understand new pain relief options)

The survey also showed that now, more than ever, those with arthritis need to understand the benefits and possible side effects associated with all arthritis pain medications. In order to do so, people with arthritis, their caregivers and families must be familiar with recent news about the two types of drugs most commonly used to treat arthritis pain - non-selective, non-steroidal anti-inflammatory drugs (NSAIDs), and another group of NSAIDs known as cyclooxygenase-2 (COX-2) specific inhibitors.

COX-2 specific inhibitors vs. Other NSAIDs

COX-2 specific inhibitors are the newest members of the NSAID class of medications. Available by prescription only, they became widely used in recent years to reduce joint pain and swelling. COX-2 specific inhibitors work by selectively blocking, or inhibiting, one of the two enzymes associated with inflammation. Some experts think that this selective inhibition may be one reason for some of the negative side effects currently associated with COX-2 specific inhibitors.

Non-selective NSAIDs were developed earlier than COX-2 specific inhibitors and have been widely used to relieve arthritis pain and inflammation for many years. Unlike COX-2 specific inhibitors, non-selective NSAIDs inhibit both major enzymes involved in the inflammatory process, COX-1 and COX-2. The non-selective NSAID category includes a number of different medications that are available in both prescription and over-the-counter (OTC) products.

Timeline of Events

To understand the current state of affairs, it is important to understand the sequence of events. The controversy started when a study published in the October 21, 2004, issue of the New England Journal of Medicine cited the COX-2 specific inhibitor, Vioxx as potentially causing “major adverse events,” including heart attack and stroke, among patients taking the drug. As a result, Merck (the drug's manufacturer) voluntarily withdrew Vioxx from the market. However, in the months following, the safety of the other available COX-2 specific inhibitors such as Celebrex and Bextra, as well as other arthritis pain medications in the non-steroidal anti-inflammatory ( NSAID ) class, were also called into question. (Related article: Pfizer continues to defend Bextra and calls it safe)

Consequently, in February 2005, the US Food and Drug Administration (FDA) convened a special Advisory Committee, made up of members of the Arthritis and Drug Safety Advisory Committees, to review the cardiovascular safety of these arthritis pain medications.

FDA Directive: Stronger Warning Labels for Some Pain Medications

On April 7, 2005, taking into account the recommendations of the Advisory Committee, the FDA issued the following directives:

• Bextra, a COX-2 specific inhibitor manufactured by Pfizer, was withdrawn from the market. (Related article: Bextra recall announced)
• All prescription NSAIDs must revise their labeling to include a “black box” warning that highlights the potential increased risk for cardiovascular (CV) events as well as the potentially life threatening gastrointestinal (GI) bleeding associated with these drugs. Celebrex, the only COX-2 specific inhibitor remaining on the US market, was included in this directive.
• All OTC NSAIDs (except aspirin) will be required to revise their labeling to include more specific information about the potential for GI and CV side effects, a stronger reminder to follow label instructions, as well as a warning about potential skin reactions.

To further evaluate the potential for increased CV risk, the FDA also announced that all NSAIDs must conduct and submit to the FDA a comprehensive review and analysis of pertinent safety data from clinical trials.

• Aleve (naproxen sodium) is supported by clinical studies conducted to gain approval of naproxen as a prescription product and as OTC that do not provide any evidence of increased risk of cardiovascular events.

Treatment Options: What Should Arthritis Patients Know?

For some people who suffer from pain associated with arthritis, their symptoms can be managed with exercise, heat/cold therapy, joint protection, assistive devices, weight control, or in some severe cases, surgery. For others, medications are needed to help manage the symptoms associated with arthritis.

When taken as directed OTC medications such as Aleve provide a safe and effective way to treat mild to moderate pain of minor arthritis. If patients have questions, they should consult their health care professional about which treatment option is most appropriate.

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Pfizer defends Bextra and calls it safe

Pfizer is still adamant that Bextra is a safe drug and the FDA might have committed a grave mistake by banning it. This comes after the FDA found that Vioxx was not a safe drug either, and also put its strongest black box warning on Pfizer's other drug Celebrex.

Julie Appleby of the American newspaper USA Today spoke to Pfizer's CEO Hank McKinnell about Bextra, drug prices, pharmaceutical advertising and his book, "A Call to Action: Taking Back Healthcare for Future Generations."

It may be recalled that after Merck recalled Vioxx in September 2004 after it was found that Vioxx's cardiovascular risks were just too high for it to be left on the market. It was later found by an FDA expert that as many as 140,000 Americans may have sustained personal injuries and of these 40,000-50,000 may be dead. However, while these pieces of data were being released, Pfizer was pumping its Cox-2 drugs until more data released showed that both Celebrex and Bextra were equally, if not more, dangerous. (Related article: Canada also decides to review Celebrex, Bextra, Vioxx, and Mobic)

After several months of debate among medical experts and publication of research that showed that both Merck and Pfizer may have oversold their Cox-2 drugs and put misleading messages in their advertisements, FDA forced Pfizer to recall Bextra in April this year.

McKinnell was reminded by Appleby that according to the FDA, Bextra's risks outweighed its benefits. She asked him if Bextra would return to the market. Like previous statements that he has been making, McKinnell said, "I don't know. I do know for many people it is the best option. It has the risk of a serious skin reaction. We think with the appropriate safety program in place, there is a possibility it could be returned to market." Merck has been making similar statements though many experts believe that this is only something that is being done as part of their legal strategy. It is highly unlikely that these drugs would ever return.

Another issue that came up in the interview was the lack of trust the Americans have in the drug industry. It is no secret that America is the most medicated nation in the world and Americans consume more drugs than anyone else. Americans also see the most direct-to-consumer ads and despite the proclamations of the pharma companies, they pay the highest prices in the world for drugs. Americans are also being attacked indirectly by the drug firms in collaboration with the FDA by not allowing them to import prescription drugs from Canada and Mexico.

When asked if Americans should trust the drug industry, McKinnell offered a scripted answer, arguing that due to the strict control of drug supply, only 1% of drugs are counterfeit here. He added, "But the public needs to understand that there is no such thing as an absolutely safe medicine. Any drug powerful enough to do good can also do some harm. ... I would not say people should trust the drugs, they should trust their doctors."

That is another debatable point that received some attention during recent hearings on Capitol Hill. It was pointed out during those hearings that American doctors do not take the trouble of keeping up to date with research, rely on pharma firms to teach them about new drugs, often cave in to pressure from patients when the ask for specific drugs (whether it will be good for them or not), and rarely disclose their conflicts of interest to their patients. (Related article: Impact of pharmaceutical promotions on a doctor's prescription patterns)

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Canada panel to review Vioxx, Celebrex, Bextra, Mobic

Canadian Health Minister Ujjal Dosanjh has announced that the Public Forum on selective COX-2 inhibitor non-steroidal anti-inflammatory drugs (NSAIDs) will be held in Ottawa on June 9th and 10th, 2005. The FDA in the US held a similar panel in February this year and based on the deliberations, it decided to ban Bextra and put a black box warning on Celebrex. While Vioxx and Bextra have been recalled worldwide, the decisions are not yet final. Both Pfizer and Merck want to fight these decisions despire overwhelming evidence against the safety of these drugs and mounting number of class action lawsuits. (Related article: Bextra recall lawsuits in Canada)

While Celebrex and meloxicam are still available in Canada, on September 30, 2004, Merck Frosst Canada Inc. voluntarily withdrew Vioxx. Pfizer voluntarily discontinued sale of Bextra in Canada along with other countries in the world on April 7, 2005, as a result of information that suggested the reported rate of serious skin reactions among Bextra users was greater than for those using other selective COX-2 inhibitor NSAIDs.

The Expert Advisory Panel is a panel of independent experts, convened by Health Canada, that will review evidence and scientific data, consider questions posed by the Department and provide advice on the safety of selective COX-2 inhibitor NSAIDS. Expert panels are frequently convened by Health Canada to access special expertise and to bring a multi-disciplinary approach to issues that require it. The panel will be made up of specialists from a number of fields that may include rheumatology, cardiology and gastroenterology, experts in biostatistics and epidemiology and representatives of patient and consumergroups. Panel members will be selected based on their expertise in areas relevant to the issues to be considered, such as the treatment of arthritisand rheumatoid arthritis, a knowledge of cardiovascular and digestive side effects and patient concerns.

A similar panel constituted by the FDA got into a big controversy after it was disclosed that panel members had financial ties to the drugmakers under review. Almost everyone did not trust the recommendations of the panel because the FDA failed to disclose the conflicts of interest. Accordingly, Health Canada is taking precautions right away. (Related article: Americans lose trust in the FDA after its mishandling of Vioxx and Bextra recall)

Health Canada says that given the relatively small size of the research, medical and patient advocacy communities in Canada, the Department recognizes the reality that panel members of this stature may have done research or had other involvement with a drug manufacturer. Where the independence of a panellist's advice could be questioned because of such involvement, Health Canada says that it has established a rigorous process to assess any potential conflict of interest. In the case of the Expert Panel, potential members have been requested to declare any material and financial interests related to selective COX-2 inhibitor NSAIDS (such as membership on any advisory groups; travel or conferences paid by a manufacturer; or shares) and any research or other ties that may affect their objectivity (such as acting as the principle investigator for any manufacturer's study). Health Canada is assessing these declarations and determining whether any conflict exists, how it could be managed (for example, by excluding the member from certain portions of the deliberations) or whether a replacement member must be invited. A summary of this information will be shared with the public at the time of the panel meeting.

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Bextra recall seems to help Celebrex sales

As was expected, after the recall of Bextra, Pfizer's other Cox-2 drug Celebrex has grabbed roughly a third of Bextra's prescriptions while Mobic, a pain reliever marketed by Boehringer Ingelheim GmbH and Abbott Laboratories Inc., has captured around 26%. For the week ended May 6, Celebrex picked up 34 percent of Bextra's prescriptions, according to Verispan, a market research company that tracks drug data. A week earlier, it grabbed 32%. (Read previous article: Bextra recall is no gain for Celebrex)

Overall sales of Cox-2 drugs, however, are down as risks of Cox-2 inhibitor drugs are declining due to their cardiovascular risks. Arthritis patients have switcher to other NSAID or are looking at other pain relief options.

In the meantime, Pfizer, that has been hurt after the recall of Bextra and a black box warning on Celebrex, is agreeing to make changes in its direct-to-consumer advertising practices for prescription drugs. Hank McKinnell, the CEO of Pfizer, is quoted by Diedtra Henderson as saying that the firm would agree to submit all drug advertising for advance review by FDA. It may be noted that Pfizer was warned for its misleading advertising related to Celebrex and Bextra.

McKinnell also said that Pfizer is still working with the FDA to change the black-box warning label on Celebrex to point out the dangers more clearly. He added that after that they will try to convince FDA to bring Bextra back on the market. This decision will be very controversial since many medical experts believe that there is a problem with the whole class of Cox-2 inhibitor drugs. Dr. David Graham, the FDA expert, actually believes that Vioxx should have never been approved.

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More studies prior to Vioxx recall were needed

Should Merck have conducted more studies of cardiovascular risk of Vioxx? This is a central question regarding drug safety worldwide. And this issue was raised during recent hearings at the Capitol Hill. John E. Calfee, Ph.D. of the conservative think tank American Enterprise Institute tried to answer this question. Below are excerpts from his testimony.

The clinical trials that provided the foundation for FDA approval of Vioxx had revealed no excess cardiovascular problems in comparison to traditional NSAID. There were some signs of risk relative to placebos) i.e., relative to the use of no pain reliever at all) but as FDA staff noted at the time, this was true of all NSAIDs. The large-scale VIGOR trial, published in November 2000 (more than a year after Vioxx was approved for marketing), revealed dramatically lower G.I. problems but unexpectedly showed a significantly higher level of heart attacks and strokes. The implications of this result were far from clear. (Related article: Vioxx should have never been approved, Dr. David Graham says)

A substantial fraction (38 percent) of heart attacks was in patients for whom low-dose aspirin was indicated (due to history of heart attacks or other cardiovascular complications) but who failed to take it (the trial avoided accepting patients on aspirin). For other patients, heart attack rates did not differ significantly. Because heart attacks were not a pre-defined endpoint in the VIGOR trial, because Vioxx had been compared to naproxen, a traditional NSAID, rather than to a placebo, and because other trials involving both Vioxx and Celebrex had not revealed significant cardiovascular problems, it was by no means obvious that Vioxx would in fact cause excess heart attacks compared to placebos. Obvious alternatives were that the result was partly a statistical fluke (always possible when selecting a non-predefined endpoint for analysis) or that the comparator, naproxen, was instead cardio-protective. Subsequent research strongly suggested that naproxen is at least moderately cardioprotective. (Related article: Merck sold Vioxx ruthlessly prior to recall)

A natural question, raised in the medical literature and elsewhere was whether Merck should immediately mount another clinical trial, presumably against a placebo instead of another NSAID, in order learn with more certainty whether Vioxx causes heart attacks. But what trial to run? Considerable debate centered on what population to study: patients with high risk for heart attacks and strokes (whose comorbidities and multiple drug use would greatly complicate the trial), or some other population? (Related article: Merck reportedly hid Vioxx risks prior to recall)

Yet running even a single trial with sufficient power to detect a doubling of a small long-term risk would involve thousands of patients spread across scores or hundreds of medical practices, at a cost of tens of millions of dollars or more, and require one to three years for design, execution and analysis. An equally important question was which drug to test. Vioxx was probably not the best target. As the FDA has repeatedly pointed out, traditional NSAIDs had never been subjected to large, long-term trials like VIGOR. The fact that NSAIDs reduce inflammation, which is implicated in heart attacks, suggests that they could prevent heart attacks. But analysis of the biological mechanisms involved in NSAIDs generates ambiguous results, suggesting that Cox-2s and other NSAIDs could facilitate rather than impede the processes that lead to heart attacks. (Related article: Merck hid risks of death from Vioxx)

Given the fact that none of the traditional NSAIDs are under patent, such trials would have to be sponsored by NIH or another public source. It so happened that in 2001, Merck was already planning a large, placebo-controlled trial (called APPROVe) to test whether Vioxx could prevent colorectal cancer. By adding cardiovascular endpoints, the APPROVe trial could detect significant cardiovascular risk. Given these circumstances, it is hard to see why Merck had an obligation to do more than run the very expensive APPROVe trial with its cardiovascular endpoints. Events have vindicated this view. The tight focus of academic and other critics on Vioxx and Merck proved misplaced. When the FDA issued its most definitive report on NSAIDs and undertook a major initiative in the NSAID market on April 7, 2005, it made perfectly clear that what began as a Vioxx incident was in fact an NSAID issue. It stated that there is no convincing evidence that Vioxx is more dangerous than other Cox-2s in terms of cardiovascular risk or that Cox-2s as a class are more dangerous than traditional NSAIDs. The agency therefore required cardiovascular warnings for all NSAIDs and urged NIH and other agencies to undertake large-scale clinical trials of traditional NSAIDs.

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So while Merck has been shouting almost from the day of Vioxx recall that it wants to bring the drug back on the market, it appears that it is not alone. Now Pfizer, the maker of now recalled Bextra and Celebrex (which is still on the market but carries a strong black box warning), is also joining the game. The company says in a statement that "Pfizer continues to believe that Bextra could be an important treatment option for certain patient populations. In the future, the company plans to discuss options with the FDA under which Bextra might be made available to those patients."

While no accurate estimates are available for deaths from Bextra and Celebrex, it is estimated that as many as 50,000 Americans are dead after taking Vioxx and there are as many as 140,000 personal injuries from Vioxx. (Related article: Merck sold Vioxx ruthlessly prior to recall)

At this point there is a lot more information is available on the dangerous side effects of Cox-2 drugs that include Vioxx, Celebrex, Bextra and others. It is, therefore, highly unlikely that any drug agency worldwide will let the drugs back on the market (FDA may be the only exception since it typically favors the drug industry rather than American people). (Related article: Vioxx and Bextra recalls have made drug approval agencies worldwide more cautious)

But it is also possible that both Merck and Pfizer may very well know the uphill task that they would face not only from the regulators but also from the patients. Statements like this may simply be designed to further their claims that the drugs that they manufactured are essentially "safe" and that is why all the personal injury lawsuits should, therefore, be dismissed.

There is also a lot of resistance from physicians on prescribing dangerous drugs like Vioxx, Celebrex, and Bextra. Primary care physicians anticipate substantial changes in their prescribing practices and in patient receptiveness to all types of drug therapy since the withdrawal of COX-2 Inhibitor drugs, Vioxx and Bextra, according to a recent survey conducted by National Analysts, a leading market research firm that consults to the pharmaceutical industry. Two of three physicians plan to be more conservative in adopting new drugs that come to market. One in three physicians predicts that patients will be more likely to abandon current therapies because of heightened concerns about drug safety. (Related article: Will you take Vioxx or Bextra on their return?)

In the meantime both Pfizer and Merck continue their legal battle with drug users worldwide. The State of Oregon, which restricted rights of Oregon residents to sue drugmakers, is going ahead with legislation that will make it easier to sue Merck and Pfizer. Similarly, a group called Drug Industry Immunity Must End in Michigan is working to bring a legislation that would allow state residents to sue drugmakers that make dangerous drugs.

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As the whole world watched in horror how Merck used aggressive marketing techniques to push Vioxx to unsuspecting users, Merck told a Congressional Committee that it is working to bring the drug back to market. It is estimated by the FDA that as many 140,000 Americans have been injured and as many as 50,000 Americans may be dead after taking vioxx. That death count "is the equivalent of the Vietnam War," Dr. David Graham, the top FDA scientist recently told an audience of about 250 doctors, academics and the public at the University of Michigan Hospital. (Related article: Vioxx should have never been approved)

And Merck knew what it was doing. The New York Times reported that as early as 2000 (four years prior to recall of Vioxx), Merck knew that Vioxx was killing people. Instead of withdrawing the drug or even warning about its cardiovascular risks, Merck decided to become even more aggressive in marketing it. According to documents made available by the House Reforms Committee, Merck urged its 3,000 Vioxx salespeople to push the drug in campaigns tagged Project XXceleration and Project Offense, in which physicians' safety concerns were described as obstacles to sales that had to be overcome. Don't bring up the heart risks, advises s a February 9, 2001, memorandum to sales people at Merck. In another training manual, sales rep were even advised on how to eat ("one small bitesize piece (of bread) at a time") when entertaining doctors. And of course, Merck salespeople were getting rich as Americans were dying. Merck offered huge bonuses to sales staff for meeting their numbers. (Related article: Merck used games like Dodge Ball to train its sales staff to avoid talking about Vioxx risks)

Merck was treated rather kindly by the Republican chairman Rep. Tom Davis at the hearings (GOP receives millions of dollars in campaign contributions from the pharma industry), but several Democratic lawmakers exposed how Merck paid no attention to deaths from Vioxx and focused on one single goal - Vioxx sales. Merck also successfully hid all risks of Vioxx and was able to counter research from outsiders through a well-organized campaign involving publishing research of its own that was favorable.

"The companies design the drug trials," Vera Hassner Sharav, president of the Alliance for Human Research Protection says in an article on The Street. "They select the subjects. They maintain and interpret the data. They select which parts get published. They choose who will become the reviewers in the prestigious medical journals. And they pick 'key opinion leaders,' who they pay handsomely" to promote the drugs."

The company is facing thousands of class action lawsuits resulting from injuries from Vioxx. Two cases that were scheduled to go on trial this quarter have been postponed to next quarter but more and more victims are coming forward, including non-Americans. The first class action lawsuit on behalf of all Italian citizens who allegedly died or were seriously injured by Vioxx has been filed recently. The suit accuses Merck of failing to properly research the known risks of Vioxx and warn Italian consumers of potentially fatal side effects. The representation of Italian consumers was undertaken by a US based Vioxx attorney in cooperation with CODACONS, the non-profit organization established by Italian law with a mandate to safeguard consumers.

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The Board of Directors of Merck today announced its election of Richard Clark as the Company's CEO and president and a member of the Merck Board, effective immediately. This means that the current CEO, Raymond Gilmartin, who was scheduled to retire next year, is being asked to leave. Gilmartin has been widely criticized for keeping dangerous drugs like Vioxx on the market for years resulting in as many as 140,000 personal injuries in the United States alone. (Read previous article asking for management change at Merck after mishandling of Vioxx recall)

Since the recall of Vioxx, the company has lost over $25 billion in market cap, faces tens of thousands of lawsuits with liabilities estimated to be as much as $38 billion. The company has, however, refused to take responsibility for even one death and has been very confrontational in its approach towards Vioxx victims. Merck has also not made any provisions for its legal liabilities and if juries award Vioxx victims with what they are asking for, Merck is headed for bankruptcy.

Merck board of directors has been very slow in acting to make management changes. It has taken them more than six months to realize that Gilmartin has been largely responsible for Merck's poor strategy with regards to handling Vioxx recall. Gilmartin, who refused to quit after the Vioxx controversy erupted last year, has tried to put his best face on his firing. "I am a strong believer that a retired CEO should be available to help a new CEO, when asked, but otherwise should clear the way for the new leader," he said today.

It will be interesting to watch if there will be any major change in Merck's strategy with regards to ongoing Vioxx litigation. Prior to hearings today in Congress, a House Committee Committee conducted an investigation into FDA’s actions regarding Vioxx and FDA’s post-marketing surveillance of drugs. As part of the investigation, the Committee requested documents from Merck to better assess Merck’s knowledge of the cardiovascular safety risks of Vioxx, and whether or not they accurately informed the public and physicians of the risk. Merck used over 3,000 field representatives in the nationwide marketing of Vioxx to physicians and medical professionals.

A review of the documents supplied to the Committee raises questions as to whether Merck was presenting a fair and balanced presentation to physicians on the safety of Vioxx. These include questions regarding the training materials Merck prepared for its sales force to use after the cardiovascular risks of Vioxx became known and before the additional warnings were placed on the label. The Committee will also question FDA and Merck about the length of time it took to add the warnings on Vioxx labels. In documents obtained by the news media, Merck was reportedly training its sales force in how to avoid questions about the safety of Vioxx.

The investigation has also led the Committee to question the structure of FDA’s Center for Drug Evaluation and Research (CDER) and the work of and the relationship between the Office of New Drugs (OND) and the Office of Drug Safety (ODS). OND is a division within CDER that reviews new drug applications. ODS is a separate division within CDER that evaluates the safety of a drug after its approval by conducting epidemiological studies and evaluating adverse event reports.

During the Committee investigation, internal problems between OND and ODS became clear. To address the vulnerabilities in the interaction between OND and ODS, FDA announced the creation of Drug Safety Monitoring Board to monitor the post-marketing risks and benefits of FDA approved drugs, improve how drug safety information is disseminated to physicians and patients by creating a drug safety website, as well as resolving drug safety disputes. The Committee was pleased with the creation of the Drug Safety Monitoring Board but remains concerned with CDER’s approach to the post-marketing surveillance of drugs.

People who are being asked to testify include Dr. Steven Galson, Director, Center for Drug Evaluation and Research (FDA), Dr. John Jenkins, Director, Office of New Drugs, Center for Drug Evaluation and Research (FDA), and Dr. Paul Seligman, Director, Office of Pharmacoepidemiology, Center for Drug Evaluation and Research, Food and Drug Administration and former Acting Director, Office of Drug Safety. In disclosures by Mother Jones, Galson, Seligman, and Jenkins are all highly sympathetic to the pharmaceutical industry and favored Merck's interests in the Vioxx case rather than worrying about American lives. They tried to suppress the voice of Dr. David Graham who tried to make public the risks of Vioxx.

Merck will be represented by Dennis M. Erb, Ph.D., Vice President of Global Strategic Regulatory Development. John E. Calfee, Resident Scholar at American Enterprise Institute, an extremely conservative think tank that favors big business is also being asked to testify.

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Are Vioxx, Celebrex, Bextra, and other Cox-2 inhibitor drugs worth the risks?

Preventing a stomach ulcer is not worth the added risk of having a heart attack, warns Dr. Byron Cryer, associate professor of internal medicine at UT Southwestern Medical Center. He is referring to the use of COX-2 inhibitors drugs marketed as Celebrex, Vioxx and Bextra, medications that were approved in the late 1990s for treating severe arthritis pain. Now, in certain cases, they have been associated with gastrointestinal ulcer complications. (Related article: Merck hid risks of death from Vioxx)

While Celebrex has been approved to remain in the U.S. market with a black-box warning, Vioxx and Bextra have been removed. They were hugely popular until last fall, when Vioxx was voluntarily pulled after clinical studies found long-term use significantly increased the incidence of heart attacks and strokes. (Related article: Vioxx side effects reconfirmed)

“While the COX-2 inhibitors are associated with a reduced rate of serious complications such as bleeding in the stomach and intestines, their gastrointestinal benefit is offset by side effects in other systems, specifically an increase in cardiovascular complications such as heart attacks and stroke,” says Dr. Cryer. He says alternatives include combining an older nonsteroidal anti-inflammatory drug (NSAID) like ibuprofen (Advil, Motrin) or naproxen (Aleve) with medications that reduce acid secretion in the stomach, such as Aciphex, Nexium, Prevacid, Prilosec or Protonix.

The anti-inflammatory drugs etodolac (Lodine) and meloxicam (Mobic) are similar in gastrointestinal safety to COX-2 inhibitors and do not appear to have the same cardiovascular risks. Another option is acetaminophen (Tylenol) or narcotics-type pain medications. He suggests you consult your physician before changing your medication regimen. (Related article: Pain relief options after Vioxx and Bextra recall)

Vioxx recall lawsuits update

In the meantime, Merck, the manufacturer of Vioxx, continues its legal battle with Vioxx victims. Despite Merck's desperate attempts to deny Cheryl Rogers, the widow of Brad Rogers who died after taking Vioxx, the right to seek damages, the trial is likely to go ahead in the coming months (there are ongoing discussions to delay the trial by several months). Clay County Circuit Judge John Rochester, who is handling the case had asked Merck and plaintiff's attorney Jere Beasley to start settlement talks. Now you may recall that Merck has not only refused to accept responsibility for even one death from Vioxx, it has also refused to engage in any out-of-court settlements. Thus, Merck went into settlement talks only after being forced to do so by the judge. Merck's strategy appears to be to drag the trial and discourage other Vioxx victims from coming forward. (Related article: Vioxx lawsuit drama in Cheryl Rogers case)

In a related development, the second Vioxx lawsuit trial scheduled to begin in Angleton, Texas on May 31 has been posponed to July. In a case similar to Cheryl Rogers', Carol Ernst is accusing Merck that its drug caused the death of her husband Robert Ernst.

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FDA incapable of drug safety in America

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FDA incapable of drug safety in America

In an excellent article by Michael Scherer published on Mother Jones, one starts to get really worried about how dangerous the alliance between the FDA and the drug industry is. The article is really about Dr. David Graham who did his best to save American lives by speaking about the dangers of drugs like Vioxx, Celebrex, Bextra, Accutane, etc. But what the article really talks about how American lives are being risked so that the pharmaceutical firms can increase their profits.

Vioxx was recalled in September 2004 by Merck when it was no longer possible to hide the fact that Vioxx was killing people. Merck successfully hid the dangers for years but at that time the evidence was overwhelmingly against it. But in August of 2004, Dr. David Graham was asked to stay quiet by his bosses, particularly Dr. John Jenkins and Anne Trontrell, when he said that Vioxx was too dangerous to be sold in America. The agency soon approved Vioxx for children.

The FDA tried to discredit Dr. Graham and his work. Dr. Steven K. Galson, the acting director of the drug-evaluation division at the FDA, called Graham’s work as “junk science.” Then he sent an email to an editor at the The Lancet, a medical journal, arguing that his data was not reliable. The FDA’s acting commissioner, Dr. Lester Crawford, in a press release, criticized Graham for evading the agency’s “long-established peer review and clearance process.” Another official made calls to at least one Senate staffer, disparaging Graham personally and professionally. At this point Dr. Graham was already a celebrity and several senators intervened as he fought to keep his job. (Related article: Vioxx and Bextra recall expose the mess at the FDA)

In a testimony before Congress, Dr. Graham pointed out that tens of thousands of Americans are dead after taking Vioxx, though Merck still refuses to accept responsibility for even one death. This may be a good time for Americans to think how far they really want to take the idea of "small government." Since the FDA can not function without the money that comes from the drug industry, it is hard for the agency officials to monintor the very same people who write their paychecks. In a survey of FDA scientists by federal investigators, two-thirds of the scientists agreed that the FDA is not capable fo monitoring the safety of drugs in America. So it sounds rather ironical that the FDA makes such a big deal about importing prescription drugs from Canada and how dangerous they are.

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One of the major controversy in the Vioxx recall drama is if Merck knew whether Vioxx was a dangerous drug. Merck continues to deny that it knew that Vioxx was killing people and claims that it recalled the drug as soon as it came to know that. Everybody else disagrees. Since the recall of Vioxx in September of last year, several disclosures have been made that clearly show that Merck may have known as early as 2000 that Vioxx was killing arthritis patients. Rather than doing something about it, Merck advertised the drug even more aggressively and engaged in a sophisticated campaign to hide the facts. (Related article: Vioxx side effects confirmed in yet another study)

Drug company-funded research and naive journalists who publish the findings are making thousands of people sick and causing hundreds more to die, says Arthur Schafer, a philosophy professor and medical ethicist at the University of Manitoba. The study that made Celebrex a household name in 2000 was rigged, Schafer claims. "I want to warn you, a lot of studies aren't real studies. They are drug company ploys to get doctors to prescribe their drugs," Schafer said to a roomful of scientists and students attending a symposium in Winnipeg last week, as quoted by Rochelle Squires in the newspaper Winnipeg Sun. (Related article: Merck and Pfizer ignored safety, focused on profits)

In papers published in academic journals and information provided to the FDA, Merck simply did not disclose the deaths from Vioxx. Last month, The New York Times disclosed that based on copies of Merck emails, it is very clear that Merck scientists knew that Vioxx was killing the patients but the senior-level management instead decided to hide the facts.

Looks as if the controversy caused by the NYT article and comments of Arthur Schafer are having its effect on academic journals. The Annals of Internal Medicine, a highly respected journal in the medical community may soon publish a correction to a Merck-sponsored study of Vioxx. The corrected version will show that Vioxx had a higher risk of heart attacks than originally reported by Merck scientists.

In a note posted on the Annals of Internal Medicine website, the editors write, "On 24 April 2005, The New York Times carried an article that discussed the ADVANTAGE trial, a Merck-sponsored study that compared rofecoxib (Vioxx) with naproxen in patients with arthritis. Annals published the primary report of this trial. The New York Times states that the Annals article reported only 6 of a total of 9 cardiac events that occurred in study subjects. Annals published the number of cardiac events (5 myocardial infarctions in the rofecoxib group and 1 in the placebo group) that the authors reported in their manuscript. The editors will try to verify the number of cardiac events reported in The New York Times article. We will print a correction if we confirm that Lisse and colleagues reported patient outcomes incorrectly."

In an interview with Bloomberg News, Annals editor Harold Sox said, "Corrections happen all the time, but corrections that materially change the message of the article are pretty uncommon." He added, "If they had told us it was 8-to-1, it would have been much different than 5-to-1." The paper was written by Jeffrey Lisse, head of Rheumatology and professor in the Medicine/Rheumatology Section at the University of Arizona College of Medicine. He was quoted in the Times story as saying that while he is listed as the study's author, Merck actually wrote the report.

There are several other instances in which Merck threatened its own scientists and others who questioned the safety of Vioxx. These findings are important since these will be crucial in the arguments by Vioxx plaintiffs that Merck knew about the dangers of Vioxx and failed to disclose them in a timely manner. Most attorneys intend to make this a central argument in Vioxx lawsuits currently in the courts.

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Despite desperate attempts by Merck, the manufacturer of Vioxx, to deny an Alabama widow the right to ask for damages for husband's death from Vioxx, the trial shall go forward. Judge Rochester ruled against a petition by Merck to dismiss a Vioxx lawsuit filed by the attorneys Beasley Allen on behalf of Cheryl Rogers (Circuit or State Court of Clay County in Ashland, Ala, case number CV 03-073, Cheryl Rogers V. Merck).

Cheryl Rogers, the widow of Howard Brad Rogers, contends that Mr. Rogers, a 42-year-old ambulance dispatcher, died from a heart attack on September 4th, 2001, after taking Vioxx for shoulder pain. This case, the country's first involving Vioxx, is slated to go to trial on May 23rd. Merck had asked the Court to dismiss the lawsuit, contending that Mr. Rogers, who died of a heart attack after being prescribed Vioxx, never took the drug. Lawyers for Beasley Allen disputed Merck's claims and said that they had evidence that Mr. Rogers took the drug before he died.

Jere Beasley, attorney for Cheryl Rogers responded, "The Order was exactly as we expected. Merck's Motion to Dismiss lacked foundation and they had to know it. It was a ploy to discredit our client, a grieving widow and single mother. We have always believed this case to be a strong one and when the jury learns how truly bad Merck's conduct has been, I am convinced they will want to punish the company. We anticipate a jury returning a large verdict. We know from Brad Rogers' medical records that he was prescribed Vioxx and that he was taking it. An autopsy proved that the drug caused his death. We will now have the opportunity to prove our case in the courtroom before a Clay County, Alabama jury.” (Related article: Merck hid risk of death from Vioxx)

According to a motion recently filed by Beasley Allen, Merck violated a protective order by disclosing personal and confidential information to the news media related to Cheryl Rogers and her deceased husband. In addition, the motion cites Merck has violated provisions of HIPAA by disclosing personal medical information pertaining to Mr. Rogers. The motion requests that the court vacate its protective order as it relates to documents produced by Merck. (Related article: Merck continues its attack on Vioxx victims)

"Releasing Merck's documents would serve the public interest by exposing its wrongful conduct over the years." Beasley adds. "Clinical tests have proven Vioxx is and was a dangerous drug. It has killed literally thousands of unsuspecting victims who trusted the company and who had no idea that Vioxx caused heart attacks and strokes."

Beasley, Allen, Crow, Methvin, Portis & Miles, P.C. has been in the forefront of the effort to have all of the cyclooxygenase-2 (COX-2) inhibitors (Bextra, Celebrex and Vioxx) taken off the market since the law firm took on its first case against Merck more than four years ago. Beasley Allen is spearheading the review of over 31,000 claims against the manufacturers of Bextra, Celebrex, and Vioxx, having filed over 160 cases to date. (Related article: Vioxx recall lawsuit update)

"We're expecting 100,000 cases in this litigation," said Russ Herman, who is leading the attorneys on the plaintiffs' steering committee in Vioxx litigation. Vioxx reportedly injured as many as 140,000 Americans and many more people from other countries worldwide. Vioxx lawsuits are expected to set a record in their size and rewards. But the process is expected to drag on for years as Merck is taking a very aggressive stance. "I hope to get this entire litigation finished in four to a maximum of five years," said U.S. District Judge Eldon Fallon, who is overseeing nearly 500 lawsuits that have been filed against Merck.

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