Scott Reuben, 51, was charged with submitting fake research for a 2007 pain management study of knee surgery patients said The Republican. The test in question was undertaken for drug maker Pfizer under a $73,000 research grant and was intended to measure the efficacy of its pain medication Celebrex when used to manage post-operative pain, wrote The Republican.
U.S. District Judge Ponsor sentenced Reuben to six months imprisonment to be followed by three years of supervised release, a $5,000 fine, restitution of $361,932, and forfeiture of $50,000. Reuben pleaded guilty to engaging in health care fraud on February 22, 2010.
According to Reuben’s defense team, said The Republican, his disreputable behavior was blamed on a bipolar disorder the team claimed was diagnosed in 2008, but that was allegedly “long-running.” Since, Reuben has also been banned from conducting future drug research and has lost his license to practice medicine, added The Republican.
United States Attorney Carmen M. Ortiz; Mark Dragonetti, Special Agent in Charge of the FDA-Office of Criminal Investigations; Susan J. Waddell, Special Agent in Charge of Health and Human Services, Office of the Inspector General-Office of Investigations; and James C. Burrell, Acting Special Agent in Charge of the Federal Bureau of Investigation (FBI)–Boston Field Division, issued the announcement.
The Republican said that Reuben’s sentence was announced last week as a result of the February guilty plea to one count of health care fraud.
At the prior plea hearing, the prosecutor told the Court that had the case proceeded to trial the Government’s evidence would have proven that Reuben obtained research grants from pharmaceutical companies for the purpose of performing research on pain management, including one from Pfizer in 2005 regarding the use of multi-modal analgesia for patients having and recovering from anterior cruciate ligament reconstruction surgery.
Despite entering into contracts by which pharmaceutical companies funded his research and provided free drug for the studies, Reuben did not perform certain studies, including one funded by Pfizer on “Perioperative Administration of Celecoxib as a Component of Multimodal Analgesia for Outpatient Anterior Cruciate Ligament Reconstruction Surgery.” Reuben’s behavior resulted in medical journals, including Anesthesia and Analgesia, to publish articles touting his multi-modal analgesia therapy despite knowing that he had falsified the research.
The Republican wrote that 50 patients were to receive the drug, while another 50 were to receive a placebo; however, while Reuben published studies indicating the test was conducted, it never was. The ruse was revealed during a 2008 “routine audit” conducted by Bay State that led to the discovery that Reuben had distorted findings from 21 studies that dated as far back as 1996, said The Republican. In 2009, Reuben terminated his privileges at Bay State, The Republican added.
In addition to Vioxx and Celebrex, some of the 21 studies involved the fibromyalgia drug Lyrica and the antidepressant Effexor XR. Reuben's study claimed to show that these drug worked well as painkillers, the Journal said. All of the studies were published between 1996 and 2008.
According to The Wall Street Journal, these studies had a great deal of influence on the practice of medicine. Because of Reuben's "research", it had become routine for doctors to combine the use of painkillers like Celebrex and Lyrica for patients undergoing common procedures such as knee and hip replacements, the Journal said.
Reuben even had the ear of the Food & Drug Administration (FDA), and had written the agency asking it not to restrict the use of many of the painkillers he studied. He often cited his fake data to make his case, the Journal said.
According to The Wall Street Journal, Reuben's fraud has caused the journal Anesthesia & Analgesia to retract 10 studies. It also posted a list of 11 others that were published in other journals on its Web site. The journal Anesthesiology said it has retracted three of Reuben's articles.
Not surprisingly, Reuben has strong ties with the pharmaceutical industry. According to the Journal, he had been a paid speaker on behalf of Pfizer - the maker of Lyrica and Celebrex - and it paid for some of his research.
Baystate Medical Center has placed Reuben on indefinite leave. He has also vacated an appointment as a professor at Tufts University's medical school, the Journal said.
Perhaps the most disturbing aspect of this scandal is that many of the drugs Reuben researched have been linked to serious side effects. Like many antidepressants, the labeling of Effexor warns that it has been linked to suicides in young people and children.
Both Celebrex and Vioxx have been linked to heart attacks and strokes, and Vioxx was actually recalled in 2006 because of these problems.
This is actually not the first time the integrity of studies involving Vioxx have come into question. Last April, we reported that an analysis of court documents uncovered in the course of Vioxx injury lawsuits found that Merck & Co. employees worked alone or with publishing companies to write Vioxx study manuscripts and later recruited academic medical experts to put their names as first authors on the studies. According to the analysis, which was published in the Journal of the American Medical Association, Merck’s involvement in producing the data wasn’t disclosed in many cases.
The study was presented this week at the American Heart Association meeting in New Orleans. At least one of the researchers recommended that physicians now avoid these types of painkillers, or use low doses, in patients with a history of heart attack or heart failure.
For their study, researchers at the University of Copenhagen analyzed the records of 58,432 patients who had a previous heart attack and 107,092 with heart failure in Denmark. Of those, 36 percent of the heart attack patients and 34 percent of the heart failure patients said they took at least one painkiller after they were discharged from the hospital.
Patients who had suffered a heart attack and were taking the painkiller Vioxx had 2.7 times the risk of having another heart attack or dying compared with patients not taking painkillers. Heart attack patients taking Celebrex had double the risk, while those with heart failure taking Celebrex had 2.3 times the risk. Heart attack patients taking diclofenac had 1.9 times the risk, while those taking ibuprofen had 1.3 times the risk, according to the study.
NSAIDs are the most prescribed medications for treating conditions such as arthritis. The Food & Drug Administration (FDA) now requires all NSAIDs to bear a black box warning regarding heart attack and stroke risks. The warnings were added to the drugs after Vioxx was recalled in 2004.
The FDA ordered Vioxx off the market in 2004 after studies showed that people who took the drug had a higher risk for heart attack. The recall came after an analysis of patients using Vioxx linked the defective drug to more than 27,000 heart attacks or sudden cardiac deaths in the U.S. from 1999 through 2003. Since then, Vioxx the subject of thousands of drug injury law suits.
Celebrex and Bextra are COX-2 inhibitors, a class of drugs that also includes Merck’s recalled Vioxx. Such medications are linked to an increased risk of blood clots, heart attacks and strokes. Pfizer withdrew Bextra from the market in 2005, and Celebrex is the only COX-2 inhibitor still on the market in the United States.
Celebrex carries the Food and Drug Administration’s (FDA) strictest “black-box” warning on its drug label, stating that it may cause an increased risk of serious cardiovascular events such as heart attacks and strokes. Despite its apparent risk, Celebrex continued to generate $2.3 billion in sales in 2007, a 12 percent increase from the previous year.
According to The New York Times, $760 million of the Bextra and Celebrex settlement would go to settle roughly 7,000 personal injury cases, $60 million will cover settlements with attorneys general in the 33 states and the District of Columbia, and $89 million will cover consumer fraud class action cases over reimbursement for money spent on the two drugs.
Pfizer said it hopes to finalize the settlement by the end of the year. A spokesperson for the company said that Pfizer would also like to include many of the remaining personal injury lawsuits the settlement. The company will fight those not settled with court motions or at trial.
COX-2 inhibitors have been the subject of safety worries since 2004, when Merck pulled Vioxx from the market. The FDA ordered the painkiller off the market after an analysis of patients using Vioxx linked the defective drug to more than 27,000 heart attacks or sudden cardiac deaths in the U.S. from 1999 through 2003. The Vioxx recall led to thousands of lawsuits.
Last November, Merck announced a $4.85 billion settlement with the thousands of people who had filed Vioxx injury lawsuits. Under the terms of the settlement, Merck set up a $4 billion fund for people who claim they suffered heart attacks as a result of Vioxx, and another $850 million fund for those who suffered ischemic strokes. Partial settlement payments started going out to some Vioxx plaintiffs last month.
The experiment was halted several years early in 2004 when heart risks occurred in a separate study on Celebrex and researchers noticed increased heart attacks and strokes in those taking Aleve in the Alzheimer's study. Scientists speculate that nonsteroidal anti-inflammatories (NSAIDs), such as Aleve and Celebrex, might help prevent Alzheimer’s by reducing brain inflammation. Although the study ended early, there was sufficient information to point to how the drugs act on thinking and memory.
Findings were posted online Monday and will appear in July's Archives of Neurology. "These were not the results we were hoping for," said co-author Barbara Martin of the Johns Hopkins Bloomberg School of Public Health. "We designed this study hoping we would see a protective effect of these drugs." The halted study included over 2,000 people ages 70 and older with a family history of Alzheimer's but no thinking problems themselves. People were randomly assigned to take standard daily doses of either Celebrex, Aleve—also known as naproxen, or a placebo. Patients were tested at the start and annually for up to three years via a battery of mental acuity tests. All three groups scored about the same at the start; however, over time, Aleve takers scored on average slightly lower than those on placebos. Celebrex takers scored slightly lower than placebo takers on most tests.
Previous, observational studies revealed that people who took the drugs experienced a lower risk of developing Alzheimer's; however, since those studies merely observed behavior and health, it’s possible those taking the pills may have had other healthy habits that lowered their risk.
Researchers hope to continue monitoring participants to determine possible delayed benefit. "The drugs have several effects in the brain and the different effects could be important at different stages in the illness," said study co-author Dr. John Breitner of the University of Washington in Seattle.
Meanwhile Celebrex maker Pfizer Inc. has begun to settle injury claims in the 7,000 cases filed by people who claim the defective painkiller caused heart attacks and strokes. Lawyers representing Pfizer have indicated the company is willing to pay as much as $500 million to resolve all outstanding cases. And, recently, the National Cancer Institute released an analysis of six Celebrex studies of 7,950 patients. According to The Wall Street Journal, analysis showed Celebrex was associated with an increased risk of cardiovascular death, heart attack, stroke, heart failure or thromboembolic event, or events related to blood clots, compared to patients not taking the drug. Researchers found patients receiving the highest dose of Celebrex of 400 milligrams twice daily had a nearly three times higher risk of heart attacks and strokes than patients not taking the drug. Patients taking a lower dose of Celebrex, 400 milligrams once daily, had a 10% higher risk of a cardiovascular event.
Celebrex and Bextra are COX-2 inhibitors, a class of drugs that also includes Merck's recalled Vioxx. Such medications are linked to an increased risk of blood clots, heart attacks and strokes. Pfizer withdrew Bextra from the market in 2005, and Celebrex is the only COX-2 inhibitor still on the market in the United States.
According to The Wall Street Journal, Pfizer has reached settlements with three law firms representing more than 200 of the thousands who sued over the drugs. Firms have been offered $40,000 to $50,000 a client to resolve Celebrex cases and as much as $200,000 a client for Bextra. The Wall Street Journal reported that unlike Merck's recent mass settlement of litigation involving Vioxx, Pfizer is attempting to resolve its Bextra and Celebrex lawsuits on a firm-by-firm basis.
Celebrex carries the Food and Drug Administration’s strictest “black-box” warning on its drug label, stating that it may cause an increased risk of serious cardiovascular events such as heart attacks and strokes. Despite its apparent risk, Celebrex continued to generate $2.3 billion in sales in 2007, a 12 percent increase from the previous year.
Last month, the National Cancer Institute released an analysis of six Celebrex studies that included 7,950 patients. According to The Wall Street Journal, the analysis showed Celebrex was associated with an increased risk of cardiovascular death, heart attack, stroke, heart failure or thromboembolic event, or events related to blood clots, compared to patients not taking the drug. The researchers found that patients receiving the highest dose of Celebrex of 400 milligrams twice daily had a nearly three times higher risk of heart attacks and strokes than patients not taking the drug. Patients taking a lower dose of Celebrex, 400 milligrams once daily, had a 10% higher risk of a cardiovascular event. The study did not look at patients taking a once-daily, 200-milligram dose of Celebrex, which represents the way the drug is most commonly prescribed.
The first Bextra trial was due to begin today in federal court in San Francisco. But a lawyer involved in the case told The Wall Street Journal that the parties agreed to adjourn the case so Pfizer could attempt to settle Celebrex and Bextra cases across the country.
Celebrex belongs to a class of drugs known as COX-2 inhibitors and is the only such drug still on the market in the US. Blocking the COX-2 enzyme impedes the production of the chemical messengers (prostaglandins) that cause the pain and swelling of arthritis inflammation. COX-2 inhibitors have been linked to an increased risk of blood clots, heart attacks and strokes. In 2004, another COX-2 inhibitor, Vioxx was removed from the market after studies linked it to more than 27,000 heart attacks or sudden cardiac deaths in the U.S. from 1999 through 2003. Another COX-2 inhibitor called Bextra was also pulled from the US market due to safety concerns.
Celebrex carries the Food and Drug Administration's strictest "black-box" warning on its drug label, stating that it may cause an increased risk of serious cardiovascular events such as heart attacks and strokes.
The National Cancer Institute's Celebrex study consisted of a combined analysis of six studies of the Pfizer pain drug, and included 7,950 patients. According to The Wall Street Journal, the analysis showed Celebrex was associated with an increased risk of cardiovascular death, heart attack, stroke, heart failure or thromboembolic event, or events related to blood clots, compared to patients not taking the drug. The risk was not affected by aspirin use.
The researchers found that patients receiving the highest dose of Celebrex of 400 milligrams twice daily had a nearly three times higher risk of heart attacks and strokes than patients not taking the drug. Patients taking a lower dose of Celebrex, 400 milligrams once daily, had a 10% higher risk of a cardiovascular event.
The study did not look at patients taking a once-daily, 200-milligram dose of Celebrex, which represents the way the drug is most commonly prescribed. Dr. Steven Nissen of the Cleveland Clinic, who has a study on lower doses underway, told Reuters that the conclusions that could be based on this latest Celebrex study were limited. "There aren't long-term randomized placebo-controlled trials for that dose, The only way we're ever going to answer these questions is with good randomized prospective data," he said. "We'll tell it like it is when the data is in."
Satpal Singh and colleagues tested various Celecoxib doses on the heart rate of Drosophila, a genus of small flies often referred to as fruit flies or vinegar flies, because of their tendency to linger around over-ripe or rotting fruit, and a good model for human cardiac pharmacology. To their surprise, administering 3 ƒ m Celecoxib—which is not much higher than the plasma levels in humans taking the drug—reduced the heart rate and increased beating irregularities, while 30 ƒ m was enough to stop the heart within one minute. Researchers were surprised at the results because Drosophila do not have COX-2 enzymes. Rather, Celecoxib could directly inhibit the potassium channels that help generate the electric current that drives heartbeat. The researchers were able to achieve similar heart-stopping results in rat cardiac cells, whereas aspirin, another potent COX-2 inhibitor, had no effect, confirming that another mechanism is at work. The drug also inhibited rat and human potassium channels expressed in a human cell line.
Singh and colleagues point out that since these arrhythmia effects bypass COX-2, it is unclear if other COX-2 inhibitors would yield similar results. They also stress it is too early to speculate on human effects, although their results suggest Drosophila—one of the most valuable of organisms in biological research and has been used as a model research organism for almost a century—are a valuable tool to investigate other COX-2 drugs.
Late last summer, authors of an article published in a special cardiology issue of The Lancet wrote that use of celecoxib after stent implantation in patients with coronary artery disease is safe, reducing the need revascularisation of the target lesion; however, an accompanying comment warned that clinical trials indicated that long-term use of celecoxib can expose patients to an additional risk of heart attack.
A 2006 review of 138 randomized trials and almost 150,000 participants revealed selective COX-2 inhibitors were associated with a moderately increased risk of vascular events, mainly due to a twofold-increased risk of myocardial infarction.
Today, Dr. Sidney Wolfe, director of Public Citizen €™s Health Research Group, sent a letter to Andrew Von Eschenbach, commissioner of the U.S. Food and Drug Administration (FDA), to raise his concerns. Calling the ad €œmisleading € and €œdangerous, € Wolfe wants the FDA to order Pfizer to immediately pull the commercial from the airwaves.
€œThe overall purpose of the ad is to make it appear, contrary to scientific evidence, that the cardiovascular dangers of Celebrex are not greater than those of any of the other NSAID painkillers, € Wolfe writes. €œFurther, it asserts that certain gastrointestinal problems are, if anything, less frequent with Celebrex than with two popular over-the-counter (OTC) painkillers.
€œThe ad violates FDA law and regulations because it contains several false or misleading statements that will lead many viewers to underestimate the cardiovascular and gastrointestinal risks of Celebrex and use it in preference to equally effective, safer alternatives such as OTC naproxen. €
Wolfe takes Pfizer to task specifically for three potentially false and misleading claims. The first controversial claim made in the spot points to the cardiovascular risks of Celebrex competitors like ibuprofen and naproxen. But as Wolfe states, €œIn a thorough review of all randomized controlled trials of older NSAIDs such as ibuprofen and naproxen, as well as the newer COX-2 NSAIDs such as Vioxx and Celebrex, published almost one year ago, the authors concluded that the COX-2 drugs, including Celebrex, did have an increased cardiovascular risk, seen most clearly with heart attacks (myocardial infarctions). € He also notes that naproxen was not associated with increased cardiovascular risk in that review.
Secondly, Pfizer says in their ad that Celebrex has the same FDA-mandated cardiovascular warning as the other NSAID drugs. While this is true for prescription drugs, OTC NSAIDs such as naproxen and ibuprofen are not required to have the same black-box warning. According to the FDA, short-term use of low-dose OTC NSAIDs is not associated with any increased cardiovascular risk. Wolfe also points out that, according to the American Heart Association (AHA), €œimportant differences exist between these agents in terms of risk of major thrombotic events. €
€œFollowing the withdrawal of both Vioxx and Bextra, € Wolfe explains, €œin each case involving increased cardiac risks of these COX-2 drugs, the FDA issued a statement requiring boxed warnings of increased cardiovascular risk on the prescription versions of all older (non-selective) NSAIDs and the remaining COX-2 drug, Celebrex. The FDA also explained, however, why the over-the-counter NSAIDs such as naproxen and ibuprofen would be available without such a boxed warning. €
The third point of contention in the ad relates to the issue of gastrointestinal damage and Pfizer €™s claim that €œa lower percentage of patients on Celebrex reported indigestion, abdominal pain, and nausea versus prescription ibuprofen and naproxen. € While it €™s true that all NSAIDs carry a warning of stomach or intestinal problems, Wolfe says, this statement does not account for €œmore serious problems, ulcers or bleeding, [which] occur equally with all NSAIDs. €
The ads take a new tack: They stress the significant risks associated with the drug early on, comparing them with the risks of rival painkillers naproxen and ibuprofen. Only later on in the ads do they mention the drug €™s benefits.
The hullabaloo around Celebrex came in the wake of the Vioxx situation. Merck €™s Vioxx was pulled from the market in 2004 due to an increased risk of heart attacks. Vioxx is a type of non-steroidal anti-inflammatory drug (NSAID) known as a COX-2 inhibitor--the same class as Celebrex. However, the FDA eventually ruled that Celebrex €™s benefits outweighed its risks and allowed it to remain on the market. Shortly after the Vioxx uproar, the FDA instituted its strictest €œblack-box € warning on all NSAIDs, including Celebrex, alerting consumers to the risk of blood clots, heart attacks, stroke, and stomach problems.
Significantly, the new ads don €™t specifically mention two recent clinical trials, according to Reuters: The first study showed that the risk of stomach ulcers was roughly the same for Celebrex users as it was for naproxen and ibuprofen users. The second trial, conducted to determine whether the drug was effective in fighting colon polyps, found an increased risk of heart attacks and strokes when compared to a placebo. The FDA is currently monitoring an ongoing clinical trial about Celebrex €™s risks.
In 2005, as health-care professionals and consumers questioned the drug €™s safety and Pfizer pulled its advertising, sales of Celebrex declined nearly 50 percent, but they rebounded sharply last year--in part because Vioxx was no longer an option. Still, the reason Pfizer attempted to get the ads back on television is that roughly 40 percent of consumers had mistakenly believed the drug was off the market.
Approximately 60,000 children are afflicted with JRA in the United States. Fifteen of the 16 panel members voted for approval, citing the short-term benefits of Celebrex and the lack of evidence of short-term safety issues. However, in an 8-7 vote (with one abstention), the panel confirmed that the drug €™s long-term safety could not be assured and they urged Pfizer to conduct long-term studies in order to prove its ultimate safety.
Medical experts and consumer watchdogs immediately challenged the decision. According to Howard Coleman, CEO of Seattle €™s Genelex Corporation, €œThousands of children have an inability to process Celebrex safely. € (Genelex conducts DNA testing in order to determine the safety of drugs and supplements.) Those children who cannot process the drug appropriately may build up dangerous levels of the drug in their bloodstreams.
Celebrex is a COX2 inhibitor, in the same class as Vioxx and Bextra--both of which were outlawed by the FDA due to risk of heart attack or stroke. Pfizer is asking the FDA to expand its approved usage of Celebrex to include minors suffering from JRA, a painful ailment affecting joints and potentially impeding growth and development. According to some reports, roughly 10 percent of all juvenile rheumatoid arthritis patients are already prescribed Celebrex €œoff-label € --meaning that the FDA has not approved its usage.
In a related story, a study published in this month €™s Federation of American Societies for Experimental Biology (FASEB) Journal investigates the issue of why COX2 inhibitors €œincrease the risk of myocardial infarction and stroke. € Researchers believe that COX2 inhibitors also inhibit the production of the COX1 enzyme, which is essential to blood-thinning capability and helps prevent the onset of clotting.
The saga of the class of drugs known as COX-2 inhibitors has provided an ongoing glimpse into a number of aspects of the multi-billion dollar pharmaceutical industry. These so-called €œsuper aspirins, € were seen by critics as over-priced painkillers that worked no better than older, safer, and far less expensive drugs. Supporters viewed them as safe and effective drugs that were easier on the stomach than other pain medications.
The three main COX-2s (Celebrex, Vioxx, and Bextra) quickly reached €œblockbuster € status and produced billions of dollars in annual sales for Pfizer (Celebrex and Bextra) and Merck (Vioxx). Massive direct-to-consumer (DTC) marketing campaigns, featuring everything from celebrity spokespersons to classic rock and roll music, kept the drugs in the public eye on a 24/7 basis.
Between January 2003 and June 2004 alone, Merck & Co. spent almost $123.9 million dollars in DTC advertising to persuade the public that Vioxx offered safe and effective treatment for acute and chronic pain associated with osteoarthritis, primary dysmenorrhea (moderate to severe menstrual pain), and other problems.
Attractive actors and celebrities, like Olympic figure skating champion Dorothy Hammil, pitched the drug in carefully orchestrated commercials set to The Rascals €™ 1968 hit €œBeautiful Morning. €
The ad-driven popularity of the drugs, and the enormous cash flow that it created, were more than adequate to stave off challenges from consumer groups, scientists, and even FDA whistleblowers who charged that all COX-2 inhibitors were dangerous in that they significantly increased the risk of heart attacks. Even proof of manipulation of clinical study data, withholding negative information, and a complete failure of the FDA drug monitoring system were not enough to bring down these drugs.
The house of cards collapsed, however, when a study designed to gain FDA approval for even wider use of Vioxx ended abruptly in September 2004 when the cardiovascular risk posed by the drug could no longer be ignored. Vioxx was pulled from the market at that time and, despite a favorable vote by an advisory panel in February 2005, has never returned. Bextra, which had other problems in addition to the heart-risk possibility, was also pulled from the market in 2005.
Litigation that had begun while Vioxx and Bextra were on the market increased dramatically once they were pulled. Today, almost 12,000 individual personal injury and wrongful death cases are pending with respect to Vioxx and there are class-actions by private insurers and individual states to recover billions of dollars in drug-reimbursement costs from the manufacturers.
Considering the one-time popularity of these drugs, the favorable FDA panel vote, and the fact that, with Vioxx and Bextra taken off the market, Celebrex was the €œonly game in town, € one would have expected sales of the only remaining COX-2 inhibitor to go through the roof. That did not happen, however. To the contrary, Celebrex sales plummeted.
To many experts (financial analysts, marketing consultants, doctors, and attorneys), the key factor in dropping Celebrex sales from $3.3 billion in 2004 to $1.7 billion in 2005 was the suspension of advertising and not the Vioxx litigation or the revelations concerning the COX-2 link to an increased risk of heart attack.
DTC advertising is now the most powerful tool in the pharmaceutical industry €™s arsenal in terms of generating revenue. This fact has prompted a growing concern among consumer advocates, scientists, and even legislators that the notion of marketing prescription drugs directly to the public is simply not a very good idea. Direct-to-consumer advertising was also brought up by Senator John Edwards during the vice-presidential debate as a severe problem in the medical field.
For the past several years, there has been an ongoing debate over controversial methods being used by pharmaceutical manufacturers to market prescription drugs. Recent high profile drug withdrawals and potential scandals have only intensified that debate; and no element of marketing is more controversial than direct-to-consumer advertising (DTCA).
While some experts maintain that DTCA actually strengthens our health care system, others are equally certain that DTCA has caused many of the problems that plague the drug industry (over-medicating, over-pricing, and exaggerated and often misleading advertising claims). There are even those who strongly urge that DTCA €œmust be banned as part of FDA reform. € (http://www.newstarget.com/z003204.html)
Many believe that any perceived benefits from DTCA are far outweighed by the problems it has caused and the burden it has placed on the FDA to regulate the content and accuracy of thousands of TV, radio, print, and online advertisements.
Before DTCA, pharmaceutical advertisements appeared only in professional publications, promotional materials, and samples intended for physicians, pharmacists, and hospital administrators.
Patients were never intended as the primary target for any form of prescription drug advertising. Thus, the commercial success (or failure) of a drug depended on its effectiveness and safety record not on slick marketing campaigns.
Today, however, the rules of the game have changed dramatically. Stiff global competition, expiring patents, generic drugs, sky rocketing research and development costs, and substantial damage awards and settlements have made marketing more important than science when it comes to turning a profit.
Moreover, a commercially successful €œblockbuster € drug can mean billions of dollars in annual profits to a company. This has served as justification for bloated advertising budgets, withholding negative information, and ad campaigns that very often become deceptive and misleading.
Today, drug advertising has become an industry unto itself and inadequately tested and hastily marketed drugs permeate the market and expose the public to great risk. How did this all come about?
The first advertising specifically intended to target the consumer appeared in the early 1980s. From that time until the mid-1990s, the bulk of DTCA appeared in magazines and newspapers.
In 1997, however, the FDA issued a draft guidance (finalized 1n 1999) that permitted the expansion of DTCA into electronic and broadcast mediums. Today, DTCA is regarded as a €œcatchall € phrase covering all information provided by drug companies directly or indirectly to consumers. This would include traditional print advertising (newspapers and magazines), television, radio, and internet ads, and brochures, newsletters, and samples distributed by physicians and pharmacists.
In 1989 DTCA spending totaled $12 million. By 1992 that figure had jumped to $156 million. When TV and radio ads were added to the mix, spending began to take off, reaching $844 million in 1997 and $1.58 billion in 1999. The figure then soared to $2.38 billion in 2001 and is now in the vicinity of $3 billion. (Between 1999 and 2003 alone, Pfizer spent about $406.3 million on DTCA advertising for Celebrex while, during the same period, Merck spent approximately $459.8 million on DTCA for Vioxx. In 2004, Pfizer spent another $117 million on Celebrex ads.)
All of this spending is not without reward, however. A recent study by researchers at Harvard University and the Massachusetts Institute of Technology analyzed the effect of DTCA advertising on consumer spending for prescription drugs.
The study found that a 10% increase in advertising of drugs within a therapeutic drug class resulted in a 1% increase in sales of he drugs in that class. When these findings were applied to the 25 largest drug classes in 2000, it was found that every $1.00 spent on DTCA yielded $4.20 in drug sales. DTCA was thus responsible for 12% of the increase in prescription drug sales or an additional $2.6 billion in 2000 alone.
Another study conducted (between 1999 and 2000) by the National Institute for Health Care Management (NIHCM) found that DTCA resulted in significant increases in retail spending. In fact, the study found that the 50 most heavily advertised drugs were responsible for 47.8% of the increase in retail spending on prescription drugs between 1999 and 2000 (some $9.95 billion) while increases in sales of some 9,850 other drugs on the retail market accounted for 52.2% of the one-year rise in retail pharmaceutical spending (about $10.86 billion).
Other significant findings were:
- Retail sales for the 50 most heavily advertised drugs rose an aggregate 32% compared to 13.6% for all other drugs combined.
- The number of prescriptions for the 50 most heavily advertised drugs rose 24.6% compared to an increase of only 4.3% for all other drugs combined.
- The 50 most heavily advertised drugs (in 2000) had combined sales of $41.3 billion (31.3% of total prescription drug sales).
- In 2000, $125 million was spent to advertise Pepsi Cola, $146 million on Budweiser beer, $169 million on GM €™s Saturn, $160 million on the top brands of Dell computers. In 2000, Merck spent $160 million on advertising for Vioxx alone.
- Each of the top seven most heavily advertised drugs beat Nike €™s ad budget of $78.2 million.
- Each of the top 15 drugs exceeded Campbell €™s soup €™s advertising expenditure of $58 million.
- DTCA accounted for 32% of all drug promotional spending (not counting the cost of samples).
While, in a perfect world, the benefits of DTCA touted by some experts would be understandable and even warranted, serious problems plague the system thereby making any such praise undeserved. Some of those problems include:
- Repeated findings by the FDA that many ads are deceptive, inaccurate, misleading, and otherwise in violation of federal law.
- The FDA is forced to expend an ever-increasing portion of its budget and manpower on policing advertising instead of more carefully investigating new drug applications and adverse reaction reports.
- DTCA takes valuable assets away from research and development.
- DTCA drives up the retail price of drugs.
- DTCA results in over medicating the public.
- DTCA results in expensive drugs being taken by patients who would be better off taking safer and cheaper alternatives already on the market.
- DTCA leads people taking drugs they do not need in the first place.
- DTCA eliminates the €œlearned intermediary € (physician) from the decision making process in many cases and, in others, doctors are placed in the awkward position of having to prescribe a drug or lose a patient.
- DTCA uses celebrities, athletes, and even retired news anchors (who have no medical or pharmaceutical training) to vouch for the safety and effectiveness of prescription drugs. DTCA uses music which is (or was) popular with the target audience in order to subconsciously influence choice.
- Warnings are confined to extremely small type at the bottom of the page or TV screen and rapidly spoken segments of commercials.
- DTCA capitalizes on the widely held but erroneous belief among consumers that €œnewer is better. €
- DTCA ultimately places marketing above science.
Many see the problem with the majority of prescription drug advertisements as being that they are just too slick. Critical information such as side effects or other hazards is often omitted or not explained in sufficient detail.
Some advertisements do not even specify what condition the drug is designed to treat. People supposedly suffering from extremely serious medical problems are often shown smiling and laughing or engaging in activities that make the drug appear to be far more effective than it really is.
As a result, the FDA often issues stern warnings to drug companies about misleading or deceptive statements or unproven claims of superiority. These warnings, however, are usually not made public. In fact, they are even sometimes ignored by the offending company or not acted upon for months or years.
Recently, pharmaceutical giants such as Merck, Pfizer, and GlaxoSmithKline have received warning letters from the FDA regarding the use of false or misleading advertisements and promotional materials.
Merck was warned as far back as September 2001 that its promotional activities and materials with respect to Vioxx were €œfalse € and €œlacking in fair balance. € In addition, Merck €™s promotional campaign minimized the now-known serious cardiovascular findings that were observed in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study and warned of by reputable medical experts.
On September 17, 2001, the FDA issued an 8-page WARNING LETTER to Merck concerning its false and misleading promotional campaign. The FDA found:
€œYou 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, and thus, misrepresents the safety profile for Vioxx. Specifically, your promotional campaign discounts the fact that 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). €
The FDA demanded that Merck discontinue promoting Vioxx to doctors for unofficial uses and found after a review of several of Merck's promotional conference calls and sales pitches that the promotions by Merck €œare false, lacking in fair balance, or otherwise misleading in violation of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations. € The FDA also required Merck to send letters about the deception to the medical community.
The letter dealt with so many improper and deceptive practices that it is difficult to imagine Merck, a leader in the field of prescription pharmaceuticals, had not formulated a plan to intentionally deceive the public, prescribing physicians, and the FDA itself as to the dangers posed by Vioxx. The FDA found:
1. False advertising in misrepresenting the safety profile for Vioxx;
2. Minimization of the potentially serious cardiovascular findings found in a prior study;
3. Failure to disclose the fact that Merck €™s explanation for the cardiovascular incident discrepancy in a prior study was only €œhypothetical € and not €œdemonstrated by substantial evidence; €
4. Failure to disclose that another explanation for the increased cardiovascular incident rate in the Vioxx group was that Vioxx €œmay have pro-thrombotic properties; €
5. Improper minimization of the Vioxx/Coumadin (warfarin) drug interaction;
6. The omission of €œimportant risk information; €
7. Unsubstantiated superiority claims against other NSAIDs;
8. Promotion of Vioxx for unapproved uses;
9. Promotion of an unapproved dosing regimen; and
10. Misrepresenting Vioxx €™s safety profile by €œminimizing the potentially serious risk of significant bleeding that can result from using Vioxx and warfarin concomitantly. €
The FDA concluded that Merck €™s €œminimizing these potential risks and misrepresenting the safety profile for Vioxx raise significant public health and safety concerns. Your misrepresentation of the safety profile for Vioxx is particularly troublesome because we have previously, in an untitled letter, objected to promotional materials for Vioxx that also misrepresented Vioxx €™s safety profile. €
Pfizer also received a warning letter (January 2005) identifying five promotional pieces for the Bextra and Celebrex which, according to the FDA €™s letter: €œomit material facts, including the indication and risk information; fail to make adequate provision for the dissemination of the FDA-approved product labeling; and make misleading safety, unsubstantiated superiority, and unsubstantiated effectiveness claims. €
The FDA claimed that the ads in question, such as the one featuring a woman playing the long version of a song on the guitar and a 27-minute long infomercial featuring €œregular people € talking about their arthritis pain, are misleading because of their overstatement of effectiveness as well as the omission of risk information.
GlaxoSmithKline was likewise warned about misleading advertisements for its hypertension drug called Coreg.
Thus, rather than demonstrate a commitment to truthful advertising, pharmaceutical companies are viewed as likely to attempt to get away with whatever they can in terms of misleading the public.
This untrustworthiness forces the FDA to divert valuable resources (money and manpower) from other important agency functions.
DTCA has been blamed for COX-2 inhibitors like Vioxx, Celebrex, and Bextra being greatly over-prescribed for years especially to patients who never needed them in the first place.
These drugs were originally touted as being easier on the stomach than other painkillers. This led to countless prescriptions being written to people for that reason alone.
Studies have shown, however, that the vast majority of people taking COX-2 inhibitors would have tolerated older, cheaper, and safer painkillers without any significant gastrointestinal problems. We also now know that these drugs are no easier on the stomach and have even been shown to cause abdominal bleeding in certain cases.
Over-medicating is a very serious problem and it is occurring more and more frequently with respect to the most advertised drugs such as those for pain, high cholesterol, gastrointestinal disorders, depression, and disorders that cause embarrassment (incontinence, herpes, yeast and fungal infections, and erectile dysfunction).
In addition, the fact that COX-2 inhibitors cost between 10 and 15 times more than cheaper, safer, and equally effective painkillers such as naproxen, ibuprofen, and aspirin was never conveyed in any of the DTCA.
This is a common occurrence in DTCA of designer drugs and one that greatly increases the cost of healthcare. Of course as healthcare expenditures rise, so does the cost of health insurance and government programs that subsidize health benefits to senior citizens and those of limited means.
In her book, The Truth About the Drug Companies: How They Deceive Us and What to Do About It, Dr. Marcia Angell, a senior lecturer at Harvard Medical School, explains that the pharmaceutical giants are €œprice-gouging € Americans. According to Dr. Angell: €œMany people, particularly senior citizens, simply cannot afford prescription drugs anymore. €
She says that a solution would be for drug companies to €œease up on price increases, since there is a growing public resistance, as well as resistance from employers and state governments. €
Dr. Peter Rost, a senior executive at Pfizer, argues that €œif price controls came in, at first there €™d be a one time fall in profits, but then they €™d start climbing again and life would go on. €
Two in three Americans now believe that drug prices are €œunreasonably high. € Right now, however, the drug companies are doing everything they can to avoid lowering costs such as refusing to legalize drug importation from Canada and trying to hook more and more people on what Angell calls €œlifestyle drugs. € Certainly, spending billions of dollars on DTCA is not helping.
While many DTC advertisements feature unknown actors or voiceovers, a significant number of ads rely upon celebrities, athletes, and famous musical recordings to entice the public. Prominent broadcast journalists such as Walter Cronkite and Aaron Brown were used to blur the line between journalism and advertising.
These reputable news anchors, who were paid handsomely for their appearances, hosted video €œnews breaks € produced by a Florida company called WJMK. These ads appeared on local public television stations between regular programs.
Another company called Healthology hires journalists to appear in video Web casts for the same purpose. Critics argue that this kind of DTCA misleads viewers by €œpackaging promotional material to look like news. €
Morley Safer of CBS appeared in hundreds of promotional videos before deciding that the work did not meet the standards of CBS news. Although all of the news anchors involved maintain that they appeared in the videos or Web casts to advertise drugs for educational purposes only, the true purpose of these videos is to promote the drugs for retail purposes.
Dr. Steven Haimowitz, the president of Heathology said that the drug companies did not write or edit the video €™s script. He claims the Web casts are €œfair and balanced € and are €œeditorial in nature. € This type of DTCA takes advantage of the relationship between the viewer and a trusted broadcast journalist.
Pharmaceutical advertising has always been regarded by many as nothing more than "an attempt to get somebody to buy something." Clearly, there is nothing scared about pharmaceutical ads that would make them more reliable or accurate than any other type of advertising.
In fact, DTCA advertising suffers from the very same shortcomings as advertising in general which Canadian economist Stephen Leacock characterizes as "the science of arresting the human intelligence long enough to get money from it".
As discussed above, DTCA leads to over-medicating when consumers become convinced that the answer to their medical or psychological problems can be found in a pill.
Many people on cholesterol lowering drugs would benefit more from a healthy diet and exercise. Most people taking COX-2 inhibitors would be much better off taking older, safer, and far less expensive alternative medications.
Lifestyle changes and therapy may be more effective for certain people than the anti-depressants or social anxiety drugs they are taking. DTCA, however, will never tell any of these people this simple fact.
Although one would like to believe that a doctor will only be guided by his medical training when deciding whether to prescribe a drug, many consumer advocates believe that is not always the case.
Doctors are often faced with patients who literally demand to be given a certain drug based on nothing more than a slick TV ad. The doctor is then faced with a decision that has little, if anything, to do with medicine.
A doctor must decide if possibly losing a patient is more important than compromising his or her ethical standards. He or she must also be willing to spend the time to convince patients that the drugs they want may not be necessary or even the safest choices.
Surveys have shown, however, that doctors too can be prone to believing that €œnewer is better. €
Some possible solutions to the DTCA problem have been proposed. One would be to make databases with complete and accurate drug information available to medical professionals and consumers alike.
While many are in favor of such an approach, there are those who are against the release of medical data which they regard as classified to anyone outside of the pharmaceutical industry or the FDA.
Many advocate increased disclosure and posting of clinical trial results. The American Medical Association has asked federal officials to create a national database where drug companies would be required to post trial results. Such a resource would allow people to see any single drug trial, whether positive or negative, in the context of other tests relating to the same drug.
The National Institutes of Health (NIH) is also seeking more disclosure. The NIH will soon be issuing rules making scholarly articles produced by scientists getting NIH grants available to the public for free. The published work should be available within one year of publication on a government website.
The U.S. is not the only country attempting to provide disclosure of medical results to consumer. After several drug-safety scandals, Britain €™s health minister said that British regulators will now begin collecting and publishing online patient reports of drug side effects.
Having more disclosure would allow doctors and patients alike to make more informed decisions about prescription drugs. It would certainly offer a reliable way to check the accuracy and completeness of claims made in DTCA or sales pitches to medical professionals.
In an expose on the pharmaceutical industry included in the November 2004 edition of the AARP Bulletin, Dr. Rost says that the pharmaceutical industry €™s €œrelentless campaign of misinformation €“ the hollow arguments that are put forward to protect profits short term- will in the end backfire. €
This claim appears to have been proven by the recent Vioxx disaster. In a different context, Bausch & Lomb is suffering from the effects of a poor response to a developing crisis with respect to one of its eye solutions. Experts agree that, in the end, it is not in the best interests of a pharmaceutical company to cover up negative data about a drug.
The important thing is to determine, with the help of a physician and truthful information from the drug companies, what the correct medical decision is for the patient. Consumers should not be making these decisions. Unfortunately, this is exactly what DTCA seeks to do as one of its goals.
A well written and informative article from NewsTarget.com (February 9, 2005) states the case against DTCA as clearly as possible.
€œThe next thing that should be done in reforming the FDA is to reverse some of the dangerous and poorly made decisions put in place by the FDA over the last few years. The most obvious of these is the legalization of direct-to-consumer advertising by drug companies. This decision was made € with the purported goal of "educating" consumers about prescription drugs. And yet the very premise is laughable. No reasonable person could possibly believe that drug companies should be advertising prescription drugs to patients who don't have medical qualifications to even understand if they should use those drugs in the first place. The idea of pushing these drugs to patients so that they go to their doctors and request them by name is medically reckless. It has no medical basis whatsoever. It is clearly just a ploy that was approved by the FDA to financially benefit the drug companies at the expense of public health.
It is this direct-to-consumer advertising, in fact, that is largely responsible for the over-medication of people with dangerous drugs such as Vioxx. This direct-to-consumer advertising continues today, and it is adding to the problem by creating an over-medicated nation where patients think they have to make a list of advertised drugs, then go to their doctor and request them by name. Many times, patients don't even have any idea what these drugs do -- they just see these images of happy, healthy people on television who have been hired to play roles in these drug advertisements, and the patients of course think they want to feel that way too, so they go to their doctor and request these drugs.
The whole system is absurd. €
While consumer advocates believe stricter rules and regulations are needed, the FDA is currently looking at a proposal which would allow drug manufacturers to simplify magazine and newspaper ads which are currently required to include a list of detailed information about risks and benefits. Critics of DTCA believe removing such information would be a step in the wrong direction.
Thus, as Pfizer brings its freeze on DTCA with respect to Celebrex to an end, the role of that marketing tool in generating massive amounts of income could not be clearer.
Pfizer is willing to advertise Celebrex again, even with dire warnings that, "Important Information: Celebrex may increase the chance of a heart attack or stroke that can lead to death," because the company knows people will then begin to ask their doctors for the drug once more despite the risk. That can only translate into increased sales of a drug that has potentially deadly side effects.
Warnings have never convinced consumers to avoid a dangerous product completely. All you need to do is consider the most extreme example; cigarettes. In that case, the tobacco companies actually advertise against smoking and, still, smoking (and death from smoking) abounds.
While Celebrex remains an FDA-approved drug, the world €™s biggest pharmaceutical company, Pfizer, has more than enough money to resurrect Celebrex through creative marketing. The results of Pfizer €™s ad campaign will no doubt give critics of DTCA more ammunition in their fight to put an end to a system they believe is the €œtriumph of marketing over science. €
The suspension of Bextra sales was due to safety concerns related to rare but serious skin reactions and cardiovascular problems. At that time, Health Canada issued a stop-sale order which ensured that Bextra (valdecoxib) would not be permitted to return to the Canadian market without further consultation with Health Canada.
The Canadian agency, which is the equivalent of the U.S. FDA, studied all of the available data on COX-2 inhibitors in general and concerning Bextra, specifically. Based on that review Health Canada has determined that “there is an increased risk of heart attack and stroke when these drugs are used for long-term treatment. Studies also showed that these side-effects can occur when Bextra is used for short-term pain relief following high-risk heart surgery. Bextra is also associated with a risk of rare but severe and potentially fatal skin reactions.”
The official announcement on the agency’s Web site (http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2005/2005_134_e.html) states: “The decision to stop the sale of Bextra is based on information submitted by the manufacturer, Pfizer Canada Inc., and consultations with external experts and the public. Health Canada concluded that there is insufficient evidence to establish the safety of the drug for its recommended use.”
“As a result of this regulatory action, the manufacturer will not be able to bring Bextra back onto the Canadian market under its present conditions of use. Health Canada has sent a letter to inform Pfizer Canada Inc. of the status of Bextra.”
The advisory concludes by stating that: “Health Canada has completed the review and agrees with the panel that available evidence indicates that COX-2 selective inhibitors and all other non-steroidal anti-inflammatory drugs are associated with an increased risk of cardiovascular events when high doses are used for long periods. However, the exact nature of that increased risk may differ from one product to another. The panel also found that the overall risk versus benefit profile for Bextra does not support the marketing of this drug in Canada under its current conditions of use.”
Another day, another negative study involving COX-2 inhibitors; the class of drugs that includes Vioxx, Celebrex, Bextra, and other NSAIDs. All along, critics of these drugs saw them as dangerous, unnecessary, overpriced, “super aspirins” that would ultimately wind up injuring and killing people.
Merck and Pfizer, however, saw the drugs as potential blockbusters and, in what has been called the ultimate triumph of marketing over science, turned Vioxx, Celebrex, and Bextra into multi-billion dollar cash cows.
The latest study from Bispebjerg University Hospital in Copenhagen, which was funded by the Danish Heart Foundation and the Danish Pharmaceutical Association, has found that COX-2 inhibitors increase the risk of death among patients who have already survived a previous heart attack, especially when taken in high doses. The data was released yesterday at the American Heart Association conference in Dallas, Texas.
The study of 58,000 Danish patients showed that heat disease patients taking 25 mg of Vioxx per day were five times as likely to die as patients not taking the drug. The figure for Celebrex was 4.2 times for patients taking a 200 mg daily dose.
While this latest study is “a cause for concern” according to lead researcher Dr. Gunnar Gislason, it really isn’t any different in theme than all of the negative evidence that sits right now in litigation files involving the most serious of the 7,000 or so remaining cases against Merck.
This is significant because Judge Carol Higbee, who controls the progress of some 3,500 Vioxx cases pending in New Jersey, has now ordered that the next 10 trials involve plaintiffs who took Vioxx for at least 18 months.
Merck has already acknowledged the existence of an increased risk of heart attacks in long-term Vioxx users and even pulled the drug from the market for that very reason. Thus, legal analysts see Judge Higbee’s ruling as one that will make it virtually impossible for Merck to duplicate its recent victory where there were many factors in Merck’s favor.
Thus, a number of litigation attorneys we spoke with late last evening were of the opinion that this latest study merely confirms, yet again, the fact that Vioxx was always a dangerous drug regardless of what Merck wanted the public to believe and despite its approval by the FDA. In fact, each attorney said basically the same thing “the second trial was a lucky break for Merck because it had a number of weaknesses in it as far as the plaintiff’s case was concerned.” The cases Judge Higbee now wants tried will have none of those weaknesses and that will only accentuate the overwhelming nature of the negative evidence.
In the recent New Jersey case that Merck won, there were a number of factors which favored Merck including: the plaintiff only took Vioxx for two months before his heart attack; he survived his injuries and actually appeared to be in surprisingly good health at trial despite the injuries he claimed to have suffered; plaintiff had a number of serious (non-Vioxx) risk factors that could have caused his heart attack; and Merck’s attorney made every effort to make it appear as if the trial judge was being unfair to the drugmaker with her rulings. The jury also was not enthralled by plaintiff’s trial attorney.
The negative evidence being referred to by those familiar with the Vioxx litigation is voluminous and quite damaging to say the least. It dates back to 1996 and never indicated a single reason why Vioxx or any of the COX-2 inhibitors should have been approved or allowed to be marketed in so cavalier a fashion as they were.
The Unbroken Chain of Damaging Evidence
Going back as far as 1996, the evidence is clear and consistent when it comes to the potential risks posed by Vioxx and the other COX-2 inhibitors like Bextra and Celebrex.
·Nov. 21, 1996 – Memo by a Merck official shows the company wrestling with the issue of Vioxx's (Rofecoxib) involvement in increased cardiovascular events. At this early date, Merck avoided a trial to prove Vioxx gentler on the stomach than older painkillers because in such a trial, "there is a substantial chance that significantly higher rates" of cardiovascular problems would be seen in the Vioxx group.
·February 25, 1997 – Internal Merck e-mail warns that if a proposed Merck trial was carried out "you will get more thrombotic events" - more blood clots - "and kill [the] drug."
·In response, Alise Reicin, later a Merck vice president for clinical research, said in an e-mail that the company was in a "no-win situation." She went on to propose that people with high risk of cardiovascular problems be kept out of the study so the difference in the rate of cardiovascular problems between the Vioxx patients and the others "would not be evident."
·The FDA approved Vioxx on May 20, 1999 for the use for the management of acute pain in adults and for relief of the signs and symptoms of osteoarthritis. (The original safety database included approximately 5,000 patients on Vioxx and did not, according to Merck, show an increased risk of heart attack or stroke).
·November 18, 1999 – Meeting of the Data and Safety Monitoring Board (DSMB) discusses concerns over the "excess deaths and cardiovascular adverse experiences" that was observed in the group using Vioxx as compared to the patients taking Naproxen.
·March 9, 2000 – Merck's research chief, Edward Scolnick, e-mailed colleagues that the cardiovascular events "are clearly there" and stated "it is a shame but it is a low incidence and it is mechanism based as we worried it was."
·Worried about the affect on Vioxx, Dr. Scolnick wrote that he wanted other data available before the results were presented publicly, so "it is clear to the world that this" was an effect of the entire Cox-2 class, not just Vioxx.
·That same month, however, the company's public statements continued to reject the link between Vioxx and increased intrinsic risk. Merck made no mention that the study found a "mechanism based" connection between Vioxx and the statistically significant increase in cardiovascular events.
·March 17, 2000 – Merck updated the label by adding reported in the "adverse events" section of the label certain "cardiovascular" reports.
·June of 2000 – Information presented at the European United League against Rheumatism, (Merck is a member and a corporate sponsor of this organization) demonstrated a statistically significant increase in hypertension and myocardial infarction.
·The VIGOR study (VIGOR - Vioxx® Gastrointestinal Outcomes Research) sponsored by Merck was submitted to the FDA in June 2000. The study was primarily designed to look at the effects of Vioxx on side effects such as stomach ulcers and bleeding. While the study showed that patients taking Vioxx had fewer stomach ulcers and bleeding than patients taking another drug, Naproxen, it revealed a statistically significant increase in the number of cardiovascular events (over 100% increase), myocardial infarctions/heart attacks (approx. 400% increase) and strokes in patients who have taken Vioxx compared to those receiving Naproxen.
·The VIGOR study was published in the November 2000 issue of the New England Journal of Medicine but did not provide detailed information about other serious cardiovascular complications such as strokes or blood clots.
·February 1, 2001 – Memo by Dr. Shari L. Targum, Medical Officer, Division of Cardio-Renal Drug Products of the FDA documented the serious cardiac events and myocardial infarctions and related deaths for participants in the study who were using Vioxx.
·February 8, 2001 – FDA Arthritis Advisory Committee Meeting discusses the VIGOR study expressed concern over the unexpected findings of cardiovascular risks and myocardial infarctions associated with the use of Vioxx that was disclosed in the VIGOR study. Merck eventually was required (April, 2002) to add some of the data as to cardiovascular events to their label.
·February 2001 – Letter by Dr. James Fries, senior professor and medical doctor from Stamford University Medical School to Merck complaining about the intimidation by Merck's investigators including the threatening of the loss of funding because of the school's discussion of cardio-vascular events associated with Vioxx.
·2001 – The concerns arising out of the VIGOR study were crystallized by Debabrata Mukherjee, Steven Nissen, and Eric Topol in JAMA in their review paper specifically highlighting the cardiovascular side-effect profile of COX-2 inhibitors.
·May 22, 2001 – Despite the mounting evidence of the strong association of Vioxx to strokes and heart attacks, Merck issued a press release entitled "Merck Confirms Favorable Cardiovascular Safety Profile of Vioxx", claiming Vioxx has a "favorable cardiovascular safety profile"
·June 16, 2001 – Merck issued another press release (released in Europe), entitled "Vioxx Similar to Placebo and Three (3) Widely Prescribed NSAID's Regarding Cardiovascular Events".
·July 11, 2001, Merck modified the package insert for Vioxx.
·August 22, 2001 – Study published in Journal of the American Medical Association by Drs. Mukherjee, Nissen, and Topol, researchers from the Cleveland Clinic, indicated that Vioxx was linked to a 200% increase in blood clots, heart attacks and strokes based on their review of previous clinical trials.
·September 2001, the American Heart Association, the National Stroke Association and the Arthritis Foundation asked Merck to test whether Vioxx increased the risk of heart attack and stroke.
·After it reviewed all of its Vioxx studies, Merck claimed there was no evidence that, in comparison with other NSAIDs, the drug increased the risk of heart problems. Merck (erroneously as it turned out) attributed the difference to a heart-protective effect it said the other drug had.
·During this time period, Merck published training materials to be used by their sales rep's, one was entitled "Dodge Ball Vioxx". Each of the 1st 12 pages lists a scenario that maybe posed by a physicians questions or concerns. Each of the last four pages contain a single word in capital letters "DODGE!" clearly indicating that Merck was training its sales reps to "dodge" the tough questions and concerns of the physicians regarding the cardiovascular risks that had started to make its way into publications.
·
September 17, 2001 – FDA sends Merck a strongly worded "Warning Letter" regarding Merck’s minimizing the potentially serious cardiovascular risks of Vioxx disclosed by the VIGOR trial and promoting Vioxx for unapproved uses. The letter demanding that Merck discontinue promoting Vioxx to doctors for unofficial uses, found after a review of several of Merck's promotional conference calls and sales pitches, that the promotions by Merck "are false, lacking in fair balance, or otherwise in misleading in violation of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations." It also required Merck to send letters about the deception to the medical community.
·April 11, 2002 – FDA instructed Merck to include in the package insert certain precautions based on results of the VIGOR studies regarding a higher cumulative rate of serious cardiovascular thromboembolic adverse events (such as heart attacks, angina pectoris, and peripheral vascular events).
·August of 2002 – Dr. Topol and Dr. Falk, a Cleveland Clinic gastroenterologist, published an editorial in The Lancet, encouraging further warnings and labeling regarding the cardiovascular effects of Cox-2 drugs. Even following these warnings, and in the face of mounting evidence for the cardiovascular side-effects of Vioxx, aggressive direct-to-consumer marketing of Vioxx continued unabated.
·April 14, 2004 – Study sponsored and conducted by Merck and Harvard Medical School and published in the journal Circulation, found an elevated risk of acute myocardial infarction associated with Vioxx but not with Celebrex. The risk was statistically significant in persons taking greater than 25 mg of Vioxx, was elevated during the first 90 days of exposure but not thereafter. These results were observed consistently in relation to several reference groups studied. What was especially noteworthy was that the elevation of relative risk was similar when Vioxx was compared with patients not taking any NSAID (Non-steroidal anti-inflammatory drugs), naproxen (e.g. Naprosyn, Aleve) or ibuprofen (e.g. Advil, Nuprin, Motrin).
·Merck asked the researchers to delete or tone down the part of the statement about this no-painkiller group, but the researchers refused, according to Daniel Solomon, a Brigham and Women's Hospital - Harvard professor who was the lead author. "We made a decision that we should let the science rule the day," he says (WSJ, 11/01/04, page A1).
·Just before the paper was published in Circulation (the journal of the American Heart Association), dated May 4, 2004, Merck removed the name of a key researcher, Carolyn C. Cunnuscio, from the study. She was employed by Merck and had worked on the study. Upon learning that Merck had removed their employee's name from the Circulation article, the current JAMA editor, Catherine DeAngelis expressed her disappointment, and rounded-off her comments by saying "Aren't they seeking truth?"
·May 14, 2002 – E-mail from Ann Trontell, FDA deputy drug safety director, warned colleagues that a Merck official had reminded her that "there had been an agreement that Merck would be informed prior to any FDA publication about one of their drug products".
·August 12 2004 – Trontell wrote in an e-mail to another official that the study's recommendation was "unnecessary and particularly problematic" because FDA funded the study and Graham (David Graham, an Associate Director for Science in FDA Drug Center's Office of Drug Safety and the FDA officer in charge of the report) also might be asked to present "alternative FDA opinion" on the drug, She added that Merck should be notified about the study results before they became public "so they can be prepared for extensive media attention that this will likely provoke".
·August 13, 2004 – John Jenkins, director of FDA's office of new drugs, wrote that Graham's conclusion uses "pretty strong language since, to my knowledge, FDA is not contemplating such a warning or labeling." Jenkins suggested that the conclusion be changed to read, "[T]his and other studies suggest an increased risk of AMI (acute myocardial infarction, or heart attack) with Vioxx use and should be considered by prescribers when making individual treatment decisions"
·Shortly thereafter, Graham responded in an e-mail response to supervisors, "I've gone about as far as I can without compromising my deeply held conclusions about this safety question. I've also shared with you the perspectives of my co-authors, and I think it's safe to say they share these same conclusions"
·August 25, 2004 – At a medical/pharmaceutical conference in Bordeaux, France, at the annual meeting of The International Society for Pharmacoepidemiology, Graham presented new data from a trial sponsored by the Food and Drug Administration that indicated patients administered Vioxx 25 mg or more per day have a risk of experiencing an acute myocardial infarction (AMI) or sudden cardiac death that is more than three times that of remote non-steroidal anti-inflammatory drug users.
·Researchers analyzed data from a subset of Kaiser Permanente patients, aged 18 to 84 years, who were treated with a COX-2-selective or NSAID (Non-steroidal anti-inflammatory drugs) between Jan. 1, 1999, and Dec. 31, 2001. In the trial, approximately 1.4 million patients contributed 2.3 million person-years of observation time. Results showed that treatment with Vioxx 25 mg/day or more conferred a 3.15-fold greater risk of AMI or sudden cardiac death compared with "remote use of any NSAID." Such a risk was also observed with lower doses of Vioxx (less than 25 mg/d), but did not achieve statistical significance.
·September 8, 2004 – Vioxx received approval from the FDA for the relief of the signs and symptoms of Juvenile Rheumatoid Arthritis (JRA) in children two years and older and who weigh at least 22 pounds.
·September 30th, 2004 – Sudden global withdrawal of Vioxx during the APPROVe study (Adenomatous Polyp Prevention Vioxx®) which was a multi-centre, randomized, placebo-controlled, double-blind study investigating the effects of Vioxx on the recurrence of neoplastic large bowel polyps in 2600 patients with a previous history of colorectal adenoma. The study participants were screened so that anyone with a history of heart disease was screened out.
·On September 14, 2004, the Data and Safety Monitoring Board received the data that eventually lead to the September 30th withdrawal. The polyp study was stopped prematurely on the suggestion of the Data and Safety Monitoring Board and a Merck statistician (James Neaton) after the investigators, who had access to all of the data, found that after 18 months treatment, patients taking Vioxx had twice the risk of a myocardial infarction compared with those receiving placebo.
·September 17, 2004 – Merck statistician and the four safety committee members had a conference call with John Baron who was the principal investigator of the polyp study and other Merck officials. After the Merck officials and Baron left the call, the four safety committee members agreed that the study had to be stopped. Neaton then called John Baron and explained to him the committee's decision. After reviewing the data that the decision was based on, Baron concurred.
·Baron then took the next week to meet with the people at Merck including the steering committee, to explain to them the decision that both the committee and he arrived at, that is halting the polyp trial.
·September 23, 2004 –The full steering committee agreed to the halting of the polyp trial. Baron then advised Merck that same day that Vioxx presented an unacceptable risk of a cardiovascular event.
·Baron spent the next few days presenting the data and the conclusions to other experts in and outside of Merck. Merck also spent the next few days reviewing all of the data from the polyp study.
·September 27, 2004 – Ranking officers at Merck decided that Vioxx needed to be withdrawn. However, the decision was made to take this decision to the board of directors.
·Merck's board of directors met on September 28. About this time, Merck notified the FDA that they needed to have an emergency meeting with them that afternoon informing them of Merck's decision to withdraw the drug.
·September 29, 2004 – Merck informed its international affiliates of the decision and asked them to withhold informing the regulators in their jurisdiction until the information was made public.
·September 30, 2004 – Merck & Co., Inc. announced a voluntary withdrawal of the arthritis and pain relief drug from the worldwide drug market. Merck's action was not ordered by the U.S. Food and Drug Administration (FDA), but was initiated by Merck based on its own findings from the clinical trial.
·Senate Finance Committee Chair Charles Grassley (R-Iowa) started an investigation into the FDA. On October 7, Grassley compared Graham's experience to that of Andrew Mosholder, another FDA scientist whose research on the link between antidepressants and suicidality in children faced from superiors at the agency. "Dr. Graham described an environment where he was 'ostracized,' 'subjected to veiled threats' and 'intimidation,'" Grassley said in a statement after committee investigators interviewed the researcher. He added, "Merck knew it had trouble on its hands and took action. At the same time, instead of acting as a public watchdog, [FDA] was busy challenging its own expert and calling his work 'scientific rumor.'"
·The Senate Finance Committee is one of three congressional committees examining FDA's actions. In addition, the Government Accountability Office has expanded its investigation of FDA's conduct in regard to Mosholder and the risks of antidepressants to include its handling of Vioxx studies.
·November 2, 2004 – FDA posted an abridged version of study conducted by Dr. David J. Graham, associate director for science in the FDA's office of drug safety. The report, dated September 30, 2004 (the same day Merck withdrew Vioxx from the market) builds upon research that he presented at a medical conference in France in late August (referred to above). "Rofecoxib [Vioxx] increases the risk of serious coronary heart disease as defined by acute myocardial infarction [heart attack] and sudden cardiac death,"
·Graham's report said. Rofecoxib is the scientific name for Vioxx. Graham defined a high dose of Vioxx as more than 25 milligrams; a standard dose is equal to or less than 25 milligrams. The study, posted Tuesday, says the recently withdrawn Vioxx increased by 3.7-fold the risk of "serious coronary heart disease" when compared to Pfizer's Celebrex. The study also says a standard dose of Vioxx increased the cardiovascular risk by 1.5 times over Celebrex. "The population impact of rofecoxib's increased risk is great because of the widespread exposure to the drug," said Graham.
·November 5, 2004, a major study, published in The Lancet, pooled data from more than 25,000 patients who participated in 18 clinical trials and 11 observational studies all conducted before 2001. The study demonstrated that patients taking Vioxx had 2.3 times the risk of heart attack as those prescribed placebos or other NSAIDs.
·In addition, the researchers found an increased risk of myocardial infarction involving both short-term and long-term usage concluding that patients taking Vioxx for only a few months were also at risk.
·The researchers specifically refuted Merck's position that there is no excess risk in the first 18 months of using Vioxx. In addition, the researchers also refuted Merck's contention that cardio-vascular involvement was dose-dependent. As to Merck's contention that in their VIGOR Study, Naproxen was cardio-protective and, therefore, influenced the outcome, these researchers found that if such evidence does exist, its effect is so small that it is not justified to claim Naproxen as a factor in the findings of the VIGOR Study.
·In concluding their findings, the researchers stated that "If Merck's statement in their recent press release that 'given the availability of alternative therapies, and the questions raised by the data, we conclude that a voluntary withdrawal is the responsible course to take.' was appropriate in September, 2004, then the same statement could and should have been made several years earlier, when the data summarized here first became available. Instead, Merck continued to market the safety of Rofecoxib. This clearly demonstrated that Merck had, by the end of 2000, sufficient statistically significant information that required the immediate withdrawal of Vioxx from its world-wide market.”
·Accompanying the study published in The Lancet on November 5, 2004 was an editorial that was even more damning than the study. Referring to the findings of the study, the editorial states "This discovery points to astonishing failures in Merck's internal systems of post marketing surveillance, as well as to lethal weaknesses in the Food and Drug Administration's Regulatory Oversight. The evidence showing that Vioxx caused significant adverse events was apparent well before data from the APPROVe trial triggered Merck's overdue intervention. This week's report by Peter Juni and colleagues will add significant weight to on-going litigation by patients who believe they were harmed by this drug."
·The editorial went on to find "the FDA tried to shore up its tarnished reputation by posting on its website an early version of a recently completed observational study into the safety of Vioxx. The report comes with a warning that it has 'not been fully evaluated by the FDA and may not reflect the official views of the agency'. The FDA investigation estimated that over 27,000 excess cases of acute myocardial infarction and sudden cardiac death occurred in the USA between 1999 and 2003. 'These cases' they write, 'would have been avoided had celecoxib been used instead of Rofecoxib'. It is unclear why the FDA could not have waited for the fully evaluated report to have been scrutinized, revised, and published according to the norms of scientific peer review. Bypassing independent peer review smacks of panic in the FDA, which is under intense reputational pressure. And, yet, its decision to try to undermine the integrity of its work shows, that the agency's senior management is more concerned with external appearance than rigorous science."
·Finally, the editorial concludes "with Vioxx, Merck and the FDA acted out of ruthless short-sighted and irresponsible self-interest." This is the most condemning editorial in a well-respected medical journal that most observers have ever seen.
·It also turns out that Vioxx, despite the slick TV and magazine ads, has not been shown to be significantly more effective than the much less expensive non-prescription anti-inflammatories such as Tylenol and Advil.
Merck Withdrew Vioxx from the Market for Purely Economic Reasons
Although Merck attempted to make the best out of a very bad situation by making it appear as if its voluntary withdrawal of Vioxx was motivated by concern for the public, the evidence does not support that position.
Most business experts have little doubt that the removal of Vioxx from the market was anything but a purely financial consideration on the part of Merck which stood to lose $700 to $750 million in the fourth quarter of 2004 alone. The lawsuits were piling up and some of the cases were close to trial.
Corporate analysts who commented on Merck’s action saw it as a sound business move under the circumstances. They did not attribute it to any sudden pangs of conscience on the part of Merck’s CEO or Board of Directors.
In fact, the evidence showed that Merck was deeply interested in widening the market for COX-2 inhibitors. That evidence included the following:
·The study (APPROVe trial) which led to Merck’s decision to voluntarily withdraw Vioxx from the market was really aimed at gaining FDA approval for Vioxx as a treatment for preventing the recurrence of colon polyps. It had nothing to do with safety and everything to do with gaining approval from the FDA for even wider use of Vioxx).
·In Merck’s open letter to “VIOXX Patients,” which appeared in newspapers across the country, Merck claimed that the study was “a clinical trial to better understand the safety profile of VIOXX.” It was actually no such thing. In fact, had the 3-year study not been halted abruptly on September 24 by the Data Safety Monitoring Board for safety reasons, Vioxx would probably still be on the market.
·Merck had already developed a new COX-2 pain reliever called Arcoxia which was being marketed in 47 countries and for which Merck expected FDA approval in the near future. While Arcoxia was not yet the billion dollar drug Vioxx was, it is clear that Vioxx was well on the way to being replaced when it was pulled from the market.
·Finally, even though Vioxx was finally exposed for what it was; a dangerous drug, Merck stated in its press release that the drug was being withdrawn despite Merck’s belief that “it would have been possible to continue to market Vioxx with labeling that would incorporate these new data” Thus, Merck would still have kept Vioxx on the market had it not met with the FDA on September 28 and been forced to confront the disastrous results of its own study.
Most experts who are familiar with the history of Vioxx from either a medical or business perspective were not surprised by Merck’s sudden withdrawal of the drug from the market. The only surprise any of these experts seems to have is why it took so long for it to happen.
Dr. Sidney Wolfe of Public Citizen was quoted in the San Francisco Chronicle (10/1/04). He stated: “This family of drugs, the COX-2 inhibitors, once referred to as ‘super aspirins,’ are turning out to be more like super disasters.”
Dr. Eric Topol, Chief of Cardiovascular Medicine and Chief Academic Officer of the Cleveland Clinic, was a co-author of the VIGOR Study discussed above. His comment to the Washington Post (10/1/04) was that Merck’s action was “the right decision about three years too late. This is the sort of thing that Merck should have studied earlier, but they were too busy refuting the warning signs.”
The Wall Street Journal (10/1/04, page B1) noted that “Merck also may face more criticism for having strenuously denied for several years suggestions by outside researchers that use of Vioxx led to heart problems. The company even published its own studies suggesting the drug wasn’t causing harm.”
The Disturbing Senate Testimony of FDA Whistleblower David J. Graham, MD, MPH
Dr. David Graham, an Associate Director for Science and Medicine in the FDA’s Office of Drug Safety is a scientist with impeccable credentials as well as a man of unchallenged integrity. He has devoted his entire professional life to making a real difference in the cause of patient safety.
Although he fought long and hard against Vioxx based upon the overwhelming evidence of its serious cardiovascular risks, he was little more than “a voice crying in the wilderness” who received no support within the FDA. He was also the target of Merck’s scorn since he posed a threat to its corporate balance sheet.
Once Vioxx was pulled from the market, however, Dr. Graham could no longer be ignored nor could his medical opinions be marginalized by his detractors. Suddenly, those in authority wanted to hear from this public servant turned whistleblower.
On November 18, 2004, Dr. Graham appeared before the Senate Finance Committee Chaired by Sen. Charles Grassley (R-Iowa). Dr. Graham delivered compelling and often shocking testimony (http://finance.senate.gov/hearings/testimony/2004test/111804dgtest.pdf) concerning the very real dangers of Vioxx and the unconscionable delay in pulling the drug from the market which has exposed the public to a degree of risk never before seen with respect to any prescription drug including sulfanilamide and thalidomide.
Dr. Graham presented the evidence against Vioxx in painstaking detail. He also set forth the disturbing facts surrounding the FDA’s efforts to suppress his research, censor and alter his scientific and medical findings and conclusions, and discredit his work.
Probably the most striking portion of Dr. Graham’s testimony involved his carefully formulated opinion that (even using Merck’s own VIGOR and APPROVe trials) some 88,000 to 139,000 Americans alone have already suffered heart attacks as a result of taking Vioxx and of that number, “30-40% probably died.” (Note that Dr. Eric Topol estimated the heart attack figure to be up to 160,000).
Dr. Graham put these astounding figures in perspective by using various examples. Most compelling, however, was the following statement:
“Imagine that instead of a serious side effect of a widely prescribed prescription drug, we were talking about jetliners. If there were an average of 150 to 200 people on an aircraft, this range of 88,000 to 138,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky. This translates to 2-4 aircraft every week, week in and week out, for the past 5 years. If you were confronted by this situation, what would be your reaction, what would you want to know and what would you do about it?”
“Even more revealing, a mere 6 weeks before Merck pulled Vioxx from the market, CDER, OND and ODS management did not believe there was an outstanding safety concern with Vioxx. At the same time, 2-4 jumbo jetliners were dropping from the sky every week and no one else at FDA was concerned.”
“At this meeting [Sept. 22, 2005], the reviewing office director asked why had I even thought to study Vioxx and heart attacks because FDA had made its labeling change and nothing more needed to be done. At this meeting a senior manager from ODS labeled our Vioxx study ‘a scientific rumor.’ Eight days later, Merck pulled Vioxx from the market, and jetliners stopped dropping from the sky.”
Merck’s Victory in the Most Recent Trial is of
Little Significance
In terms of what Merck’s recent victory means litigation-wise, Merck’s defense team is experienced enough to know it means very little since it is somewhat like trying to stop a tidal wave with a sponge.
Merck would have to win virtually all of the remaining 7,000 (and growing) cases to stave off a financial catastrophe since each negative verdict has the potential of being in the millions of dollars. Even scattered losses for Merck can add up to a financial disaster.
Is such a possibility realistic? Not even Merck’s attorneys could believe that. Shortly after the verdict we spoke with several seasoned trial and appellate attorneys who were all of the same opinion; Merck’s victory means little, if anything, to the overall litigation situation the company faces. This is especially true since Merck has repeatedly stated that it intends to fight each case individually.
The reason for this is that each case Merck wins only serves as a victory on the particular facts of that case since every plaintiff’s claim is factually different and the law allows each injured party to have a chance to prove his or her case.
Each case that Merck loses, however, has a cumulatively negative effect since it has gotten another chance to prove its lack of culpability and has failed. As one attorney put it: “Each plaintiff has only one chance to prove he’s right in order to win, but Merck has to show it’s right another 7,000 times in order to walk away without being liable. The likelihood of that is zero.”
It is highly unlikely that there will be a confluence of all of the factors that favored Merck in any of the remaining cases. Many of the remaining cases involve factors which will make Merck’s job much harder.
These cases involve deaths, long-term use of Vioxx, plaintiffs without additional risk factors for heart attack, and different plaintiffs’ trial attorneys (a factor which cannot be underestimated).
In addition to the immediate problems Merck faces in New Jersey, Texas (the site of the $253 million verdict against Merck) is still not finished with the company since the state itself has brought charging Merck defrauded it out of hundreds of millions of dollars in Medicaid payments by misrepresenting the safety of Vioxx for several years. While Texas was the first state to do this, it probably will not be the last.
In addition to $168 million in damages, the state is seeking additional civil penalties. Texas Attorney General Greg Abbot believes the state can prove total damages in excess of $250 million including treble (triple) reimbursement of $56 million (or $168 million) for five years of filled Vioxx prescriptions.
It is estimated that 700,000 Vioxx prescriptions were filled through Medicaid during those five years in Texas alone. Abbot sees these prescriptions as part of a willful misrepresentation on Merck’s part as to the safety of the drug. To him, the entire affair represents nothing more than “a prime example of a company’s drive for profit steamrolling its duty to be safe.”
Clearly, as Merck’s legal problems mount, no one victory will mean very much while each loss will be extremely damaging indeed. Each loss will make manageable personal injury settlements impossible and virtually guarantee the success of the types of actions brought by Local 68 and the state of Texas. This could spell financial ruin for Merck.
Finally, if Merck is found to have knowingly, or even carelessly, engaged in conduct which forces the company into Chapter 11 or otherwise destroys its once enormous profitability or stock value, disgruntled and very angry shareholders will no doubt explore the possibility of commencing a stockholders derivative suit to recoup their investment losses.
Judge Higbee has scheduled a hearing with respect to her decision to proceed with the most serious cases next. That hearing is scheduled for Thursday at which time Merck’s attorneys hope to convince the judge to change her mind.
Plaintiffs’ attorneys welcome the judge’s plan as a way to move the litigation along. While no definite figure is available, estimates put the number of 18-month (New Jersey) cases at somewhere between 1,400 and 2,100.
Merck’s lead outside attorney Ted Mayer has stated that: “We are confident in our defense of 18-month cases.” One has to wonder, however, if that is anything more than saber-rattling given the additional negative evidence that will directly impact Merck in those particular cases.
Since it is unlikely Judge Higbee will accede to Merck’s request that the court change its decision with respect to the order in which Vioxx cases will be tried, Merck must begin to accept the very real possibility that the next several months may significantly affect the financial future of the world’s fifth largest pharmaceutical company, and not in a positive way.