Vioxx

Vioxx (Safe and Effective,  Drug)
Interest of	Brandy Vaughan
Big Pharma painkiller that might have killed 500.000 people in the United States alone, after the manufacturer Merck withheld evidence of its dangers.

Vioxx is a powerful painkiller from the Big Pharma manufacturer Merck.

More than 20 million people worldwide took Vioxx before Merck withdrew the drug in September 2004, when it was suspected of having caused more than 55,000 deaths from stroke and heart attacks. A 2007 class action settlement included 3,468 deaths among 27,000 cases, for a $4.85 billion payment.

Statistics suggest Merck actually killed many more people than this. The year Vioxx was introduced, 1999, showed the largest recent rise in American death rates. The year after Vioxx was pulled from the market, American death rates underwent a substantial and completely unexpected decline. This drop corresponds to roughly 100,000 fewer deaths per year. The numbers suggest that Vioxx may have caused more than 500,000 premature deaths in the United States alone.

In the UK, ‘the scale of the Vioxx case outstrips the Thalidomide scandal that led to the 1968 Medicines Act governing the way in which drugs are regulated. The MHRA which approves drugs in the UK, has launched an investigation into whether Merck deliberately withheld information on Vioxx when it applied for a British license in 1999….This case highlights the way pharmaceutical companies can distort scientific data on a product to exaggerate its benefits.’

Recall

Concerns about Vioxx's safety reached the US Food and Drug Administration as early as 2000, but the FDA failed to act, in part due to:

"laboratories and network of independent drug safety experts in favor of hiring more people to approve drugs. ...the agency (is) increasingly reliant on and bound by drug company money."

It was not until 2004 that strong, publicly available research tied Vioxx (a COX-2 inhibitor), to a significant increase in heart attacks among users. The drug was pulled off the shelves that fall. Following the Vioxx recall, many faulted Merck's over-the-top direct-to-consumer advertising. According to Public Citizen's Health Research Group director, "Advertising and promotions played a major role in making people think Vioxx was safer and more effective than it is."

The New York Times cited Vioxx and other COX-2 drugs as "perhaps the clearest instance yet of how the confluence of medicine and marketing can turn hope into hype - and how difficult it is for the Food and Drug Administration to monitor the safety of drugs after they have been approved for the market."

Merck responded to the Vioxx recall by launching a public relations campaign to salvage its image and portray its pulling the drug in as positive a light as possible. The campaign included three full page ads in seven prominent newspapers; several television appearances and testimony before Congress by the company's CEO. However, leaked emails and other internal documents indicated that the company knew about the side effects long before the drug was withdrawn. According to Merck's media relations director, "the mantra has been openness, integrity and transparency."

The fact that a member of the FDA openly admits that there is an intimate relationship between the regulator and the industry suggests that there is friction between different departments within the FDA. When Graham and his team concluded the study on Vioxx for example, the Office of New Drugs allegedly pressured him to change his conclusions and recommendations and told him he would not be allowed to present his findings if he did not do as he was told. The FDA demanded that he tampered with figures estimating that users of the drug had suffered at least 38,000 excess heart attacks and sudden cardiac deaths. Graham also received an internal email from the FDA stating that the regulator was ‘not contemplating’ a warning against the use of high-dose Vioxx.

The MHRA licensed Vioxx in the UK in 1999. Five years later when Vioxx was withdrawn by Merck, the EMEA decided to carry out a safety review and the MHRA was investigated by the Health Committee in the House of Commons. In its report, regulatory failure was partially blamed on the regulator’s commitment to serving the industry rather than the public.

Doctored science and lawsuits

After Merck withdrew Vioxx, evidence surfaced that the company had withheld early evidence of its dangers. In December 2005, the editors of the prestigious New England Journal of Medicine issued a rare "Expression of Concern" regarding a 2000 Merck report on Vioxx in which "Merck scientists failed to report three nonfatal heart attacks among the Vioxx users. The total number of heart attacks among the drug users was 20 ... not the 17 reported." Merck argued that the heart attacks occurred after the study cut-off date, but the editors maintained that they should have submitted an update, as "the three heart attacks occurred shortly after the study's end." According to the editors, Merck:

"withheld more relevant data about strokes and other heart problems linked to the drug, producing inaccuracies and deletions that 'call into question the integrity of the data'."

"Experts disagreed on how medically significant the three heart attacks were, but agreed that the decision not to include the cases could bolster claims in thousands of lawsuits against Merck and that the company was deliberately withholding data about the drug's health risks," reported the Los Angeles Times. "The accusations by the prestigious New England Journal of Medicine could hurt Merck's ability to defend itself in the 6,500 lawsuits blaming Vioxx for heart attacks, strokes and deaths. Analysts have estimated that the cases could eventually cost the company $50 billion."

In November 2007, it was reported that Merck had agreed to pay $4.85 billion to settle 27,000 lawsuits in death and injury claims from victims and their relatives. The settlement came after nearly 20 Vioxx civil trials over two years. Merck lost the first civil suit, paying $253 million, but won most of the rest. According to Alex Berenson of the New York Times in November of 2007:

"The settlement will help put Vioxx behind Merck, as well as sharply reduce its Vioxx-related legal defense fees, which are now running at more than $600 million annually. The deal becomes binding only if 85 percent of all plaintiffs agree to drop their cases and take the deal. ... Based on the fact that the 27,000 suits cover about 47,000 sets of plaintiffs, the average plaintiff will receive just over $100,000 before legal fees and expenses. ... While eye-popping, the settlement payment represents less than one year's profits for the company."

In April 2008, the Journal of the American Medical Association (JAMA) published two studies analyzing Merck documents that had surfaced during Vioxx litigation. Collectively, they concluded that Merk had violated scientific publishing ethics by ghostwriting dozens of academic articles and minimized the impact of patient deaths in its analyses of clinical trials.

According to one study, medical papers on Vioxx were often prepared by ghostwriters and subsequently attributed academic investigators who often did not disclose financial support. Another study concluded that Merck did not provide to the FDA, nor make public the evidence that Vioxx was linked to increased risk of death. Five of the six authors of the two JAMA studies had served as paid consultants to plaintiffs' lawyers in Vioxx lawsuits. A Merck researcher called the findings "false and misleading."

In August of 2008, an analysis of Merck's internal documents were published in the Annals of Internal Medicine. They concluded that Merck carried out a clinical study of Vioxx in 1999, primarily to support their marketing campaign before launching the drug. According to Merck, the study was done "to test side effects of the painkiller Vioxx."

The 1999 "ADVANTAGE" study compared Vioxx to the widely-used painkiller (Naproxen), in order "to accelerate uptake and advocacy for Vioxx," according to the Merck documents disclosed during litigation. According to another document, (a nomination of the 1999 study for a marketing award), the study was, "designed and executed in the spirit of Merck marketing principles." According to the Wall Street Journal, carrying out clinical studies for marketing purposes:

"would raise ethical and scientific questions, from whether study participants were unknowingly -- and needlessly; put in harm's way, to whether a company's research is reliable."

Again, the authors of the Merck document analyses were paid consultants in Vioxx lawsuits against Merck. Merck responded to the analysis in an open letter, claiming that the analysis "contains numerous inaccuracies." For example, the analysis concluded that the 1999 Vioxx "ADVANTAGE" clinical trial was designed by one of Merck's marketing units. However, Merck maintained that the trial was "designed, conducted, analysed, interpreted and published by the scientific department of Merck’s U.S. Human Health organization." Merck also stressed that there were legitimate, scientific reasons for conductin the trial; such as assessing the "gastrointestinal tolerability of VIOXX compared to naproxen."

In April 2009, an Australian class action revealed tactics used by Merck to intimidate or discredit doctors or researchers who were critical of Vioxx. According to an internal email, "We may need to seek them out and destroy them where they live". Merck staff produced a list of people who they wished to "neutralize" or "discredit".

Merck promotional campaign

In June 2005, the ad agency Ogilvy & Mather Worldwide launched the first promotional campaign ever for Merck - a $20 million, 6-month campaign with the slogan:

"Merck. Where patients come first."

The campaign was planned before the company was forced to withdraw Vioxx and evidence came to light that Merck not only ignored evidence that Vioxx caused heart complications, but also heavily marketed the drug. The major goal of the promotional campaign was "to build emotional ties between Merck and consumers". One television commercial shows children reacting in charming confusion to requests to define "measles," "mumps" and "chicken pox":

"Most kids today don't have a clue about diseases adults remember, thanks to Merck's scientists." The female announcer adds, "We've invested billions to research heart disease and asthma. Now we're trying to make Alzheimer's, diabetes and cancer history too."

Over 40% of the ads in the campaign are devoted to information about "access programs"; or efforts to provide consumers with prescription drugs either free or at reduced prices. According to Michael Guarini, managing director for Ogilvy & Mather's health care practice:

"We want the public to understand a little more who Merck is and raise the awareness of Merck, but we also want to communicate useful information. While the Vioxx scandal had tarnished Merck and public opinion of drug companies in general was low, it's always good to engage in dialogue, to make sure the public has true, balanced, accurate information."

Censoring spokes-doctor turned critic

In June 2005, U.S. National Public Radio's Snigdha Prakash reported:

"New documents obtained by NPR suggest that even as Merck was making Vioxx into a bestseller, the company was putting pressure on independent doctors. The company's apparent aim: to keep them from discussing evidence of Vioxx's potential safety problems. The documents show that Merck exerted pressure not only on individual doctors, but also on several of the nation's top medical schools."

Merck's campaigned to recruit physician Gurkirpal Singh of Stanford University as a Vioxx spokesperson "because he was a senior researcher on a seminal study of arthritis patients." Starting in 1998, Singh became a Vioxx booster and was paid $2,500 per speaking engagement by Merck. However, in 2000, a study suggesting heart problems among Vioxx users worried Dr. Singh and he requested the data. According to Dr. Singh in an interview with NPR:

"I wanted to know how many heart attacks, how many strokes, how many deaths were occurring in each one of the groups, and what were these actual number of patients at risk, and how many ended up having an event."

Merck originally promised to share the information with Dr. Singh, but never did. When Dr. Singh began including his concerns in his public presentations on Vioxx, Merck began closely tracking his activities. According to NPR, almost a dozen Merck executives were involved in tracking Dr. Singh. According to an October 4, 2000 email sent by a senior, regional executive who had supervised his scientific handlers:

"I have in excess of 80 e-mails pertaining to interactions with Dr. Singh from March 1999 to present. The following is my best recollection of what has happened. Because of the sensitive nature of the following, I strongly encourage you not to share with anyone unless they clearly have a need to know."

As Singh's public criticisms of Vioxx continued (he was by this time, promoting Vioxx's rival, Celebrex, while being paid by Pfizer), Merck began calling his superiors at the university. According to Stanford medical professor James Fries:

"(I) received a call from a medical director at Merck, stating that someone on my staff had been making wild and irresponsible public statements about the cardiovascular side effects of Vioxx." According to Dr. Fries, the representative "hinted there would be repercussions for Fries and Stanford if Singh's statements didn't stop. He was left with the sense that Merck's financial support to Stanford was at risk."

Another attempt to rehabilitate Merck's image

According to the PR firm APCO Worldwide in May of 2006:

"APCO Worldwide is supporting Merck's PR efforts for the controversial arthritis drug Vioxx, which was found to increase heart attack risk in patients."

APCO was founded by Arnold & Porter, one of Washington D.C.'s largest law firms, also well known as a tobacco industry law firm. According to the Wall Street Journal, the PR boost came as Merck:

"acknowledged that it misidentified a statistical method used in the study that led it to pull Vioxx from the market."

The admission calls into question Merck's claim that patients were only at risk if they took Vioxx for 18 months or longer. According to doctors who oversaw the study, risks associated with Vioxx were evident as soon as four months into taking the drug. As of May of 2006, there were over 11,000 Vioxx related lawsuits filed against Merck. The company retained Burson-Marsteller for a $20 million "image campaign," after withdrawing Vioxx in 2004.

 

Related Quotation

Page	Quote	Author	Date
Ron Unz	“A cursory examination of the most recent 15 years worth of national mortality data...offers some intriguing clues to this mystery. We find the largest rise in American mortality rates occurred in 1999, the year Vioxx was introduced, while the largest drop occurred in 2004, the year it was withdrawn. Vioxx was almost entirely marketed to the elderly, and these substantial changes in national death-rate were completely concentrated within the 65-plus population. The FDA studies had proven that use of Vioxx led to deaths from cardiovascular diseases such as heart attacks and strokes, and these were exactly the factors driving the changes in national mortality rates. The impact of these shifts was not small. After a decade of remaining roughly constant, the overall American death rate began a substantial decline in 2004, soon falling by approximately 5 percent, despite the continued aging of the population. This drop corresponds to roughly 100,000 fewer deaths per year. The age-adjusted decline in death rates was considerably greater.”	Ron Unz	17 April 2012

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