Vexing Vioxx

THE NEW England Journal of Medicine's recent retraction of a 2000 article that helped establish the popularity of Vioxx, the controversial painkiller, should give doctors, hospitals and journal authors reason to think harder about how drug safety information is processed. The retraction, published last month, stated that the article's authors -- including scientists in the employ of Merck & Co., which makes Vioxx -- knew in advance of publication that 20 out of more than 2,000 patients taking part in a study of Vioxx suffered from heart attacks after taking the drug, not 17 as the article reported. They left out the information, they say, on the grounds that the three heart attacks in question occurred after the study had technically ended. But as a result, the level of heart attack risk associated with Vioxx appeared in the article to be slightly lower than it should have been.
It is true that Merck disclosed the existence of the three heart attacks to physicians who were sent a copy of the original article, the main purpose of which was to establish that Vioxx caused fewer stomach problems than other leading painkillers. More important, Merck revealed the three additional heart attacks to the Food and Drug Administration, well before the journal article appeared. Had Merck not done so, the company would have been liable for criminal prosecution: The government does have the tools to prosecute companies that lie or withhold information from the FDA, and it does use them.
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In other words, this revelation raises legitimate questions about the relationship between scientists, who are often paid by drug companies, and medical journals, which should do a better job of stating authors' conflicts of interest. It should also lead doctors who prescribe drugs and are ultimately responsible for understanding their side effects to read such journals with greater skepticism.
It does not, however, alter our view that the courts are the wrong place to resolve disputes about drug safety. The New England Journal of Medicine's retraction is expected to have an enormous impact on the thousands of lawsuits against Merck. But it is still not clear that doctors prescribing Vioxx several years ago would have behaved any differently had the journal article showed that the risk of heart problems was very slightly higher. Scientific judgments about the risks and advantages of drugs are not black and white -- which is why they are best made by scientists and by the regulatory agency that employs them, not by jurors through the lens of hindsight.

Former Vioxx user planning to sue

The painkiller Vioxx continues to cause former and current patients taking the drug to suffer, and many are taking their stories to the courts with the realization that a drug which was supposed to help may have actually harmed them.
Jacksonville attorney Cy Jenkins is one of those people, and he currently has a lawsuit pending against the maker of the drug.
With seriousness and concern, Jenkins displayed a bottle of nitroglycerin he had in his pocket, which he is prepared to take at the signs of a heart attack.
“I walk around now with a bottle of nitroglycerin in my pocket, because I just don't know if I will have another heart attack,” Jenkins said.
Unaware of exactly how Vioxx has damaged his body, Jenkins lives in fear for his life. His medical bill of $130,000 has also damaged more than his pocketbook.
“I can't get insurance now,” he said. “Merck should have disclosed this before. I know I'll never be the same, because of it, and my family will never be the same.”
On Sept. 30, 2004, Merck & Co., the manufacturer of Vioxx, announced a world-wide recall of the drug after a study revealed it could cause serious cardiovascular problems, including heart attack and stroke, if taken for 18 months or longer.
It is the largest drug recall in history, according to the Web site www.vioxxnews.com.
Jenkins began taking Vioxx in May 2001.
“I took Vioxx for back problems on and off for two years,” Jenkins said.
Then Jenkins woke up with a tingling sensation, and once at the hospital, he discovered he'd had a heart attack.
Fifteen months later, Jenkins suffered another heart attack.
“Doctors said there was no evidence when I had the other one of a blockage. I had taken Vioxx before the heart attacks and in-between them. I can't understand why there were no indications of another blockage 15 months before,” Jenkins said.
In 2000, the Vioxx Gastrointestinal Outcomes Research compared Vioxx and the traditional non-steroidial anti-inflamatory drug naproxen among 8,000 patients and found the risk of cardiovascular problems, including heart attack, chest pain, stroke, blood clots and sudden death, was more than two times higher in the Vioxx group than in the control group, according to the Web site.
Despite findings, the company continued to “aggressively market” the drug.
“The mainline is this isn't just a corporate money thing. The company was dealing with lives, and they should have disclosed the information sooner,” Jenkins said.
According to the Web site, the Federal Food & Drug Administration released information in November 2004 which indicated Vioxx may have contributed to at least 27,785 heart attacks or sudden cardiac deaths from 1999 to 2003.
About 20 million people took the once-popular painkiller, and the company faces billions in potential payouts stemming from about 7,000 pending state and federal lawsuits.
In the first Vioxx lawsuit in Texas, more than $253 million was awarded on Aug. 19, 2005, to the widow of a Vioxx user who died of fatal arrhythmia. In the second lawsuit, since the plaintiff had only taken Vioxx for two months, Merck won the case, and during another trial, the company disclosed the information about the drug, and a mistrial was declared, Jenkins said.
Thousands of other cases across the nation are pending, according to the Web site.
“Vioxx has changed my life,” Jenkins said. “I would encourage people to consult with an attorney if they are taking it, especially if they've had a heart attack.”

Health Canada Prohibits Sale Of Bextra In Canada

Following a review of safety information, Health Canada is informing the public that Bextra, an anti-inflammatory drug used to treat arthritis and pain, will not return to the market. The manufacturer voluntarily suspended sales of Bextra in April 2005 due to safety concerns related to rare but serious skin reactions and cardiovascular problems. Health Canada issued a stop-sale order which ensured that Bextra (the brand name for valdecoxib) would not return to the market without further consultation with Health Canada. Bextra is one of a small group of drugs called COX-2 selective inhibitor non-steroidal anti-inflammatory drugs. A review of the available evidence for other drugs from this group indicates 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 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. Following the voluntary withdrawal of another COX-2 selective inhibitor, Vioxx, from the worldwide market on September 30, 2004, a team of Health Canada experts initiated a review of related drugs to determine whether they had a risk of similar cardiovascular side-effects. Health Canada consulted external experts and the public as part of the COX-2 Expert Advisory Panel that met in June 2005. 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.

Manatee residents sue Merck

MANATEE - Following a wave of litigation from across the country, the first three lawsuits have been filed from Manatee County against the New Jersey-based maker of the drug Vioxx.
The lawsuits, being litigated by attorney Brenda Fulmer of Tampa, join thousands of actions filed against Merck & Co. Inc. The three Manatee plaintiffs allege the company knew Vioxx posed an increased cardiovascular risk but didn't adequately inform the public. Vioxx is a painkiller usually used to treat osteoarthritis and acute pain.
Francis Gordon Harper Sr., Jacqueline Thibodeau and Hazel McDade of Manatee County separately claim they suffered heart attacks between 2002 and 2004 as a result of taking Vioxx.
The lawsuits include counts of fraud, liability, negligence and negligent misrepresentation.
Thibodeau's and McDade's lawsuits, filed in October, were removed from circuit court in Manatee County to federal court in late November. Harper's lawsuit, filed three weeks ago, remains in state court.
The attorneys representing the three plaintiffs and Merck could not be reached for comment Wednesday.
The three Manatee residents said in their lawsuits that a study known as the VIGOR Protocol showed those who took Vioxx suffered a higher rate of adverse cardiovascular incidents than those taking a comparable drug. Other studies showed that Vioxx use increased risk of hypertension and stroke.
The Food and Drug Administration admonished Merck several times for making false claims in some of its promotional pieces, the lawsuits argue. In September of 2004, Merck announced that a long-term study on Vioxx use would be discontinued because of safety concerns. Days later, it withdrew Vioxx from worldwide markets. The company has acknowledged that after 18 months of use, Vioxx can increase chances of a cardiovascular episode.
Merck said it planned to transfer the first two Manatee lawsuits to the U.S. District Court for the Eastern District of Louisiana, where an additional 148 Vioxx product liability cases will be heard.
The first federal Vioxx case was declared a mistrial Dec. 12 when the jury couldn't unanimously agree on a verdict. The case involved a Florida man who took Vioxx for 23 days and then died of a heart attack.
At the state level, Merck won a Vioxx-related case in New Jersey last month involving a postal worker who claimed he had a heart attack after using Vioxx for two months. A state court jury in Texas, however, decided in August that Merck should pay $253 million to the family of a man who used Vioxx for eight months.
Three weeks ago, the New England Journal of Medicine asked Merck to correct the VIGOR Protocol study it published in 2000 because the authors deleted some heart attack-related events from its conclusion.
The three Manatee County suits were filed before the publication's request.

Drug companies making more study data public

Drug companies are making public more information about medical studies they are conducting, but some still withhold key details, a new analysis of a federal registry finds.
Merck, stung by allegations that it hid information on Vioxx's dangers, gets somewhat better marks in the new analysis -- covering May 20 to Oct. 11 -- than it did in an earlier one. However, Pfizer, GlaxoSmithKline and Novartis are lagging, according to the report in today's New England Journal of Medicine.
Run by the National Library of Medicine, the registry, www.clinicaltrials.gov, was created in 2000 as part of an overhaul of Food and Drug Administration monitoring. It requires certain types of studies to be listed, such as late-stage experiments involving life-threatening illnesses.
But it didn't get wide participation from industry or many voluntary listings until September 2004, when editors of leading medical journals said they would no longer publish results of any studies that were not first listed in a public registry.
The idea was to make it easier for scientists, regulators and the public to cross-check what studies were being done on a drug and get the big picture of risks and benefits. The registry includes studies by universities, governments and industry, but concerns about openness center on industry.
The new analysis focused on whether company listings revealed the name of the drug or device being tested and the main outcome being measured, such as death or cancer recurrence within five years.
Pfizer was worst on giving names, and Glaxo named the drug in all but one of its new listings; Merck now has the best record of naming drugs but did poorly on listing the outcome being measured.
Novartis gave the outcome measure for a mere 3 percent of its registered studies.
A Merck spokeswoman said the company considers information about the precise outcome it is testing to be private information that would damage its competitive position.