©2009 Angel Reyes
www.ReyesLaw.com

©2009 Angel Reyes
www.ReyesLaw.com

No Legal Shield in Drug Labeling, Justices Rule
The New York times
By ADAM LIPTAK
Published: March 4, 2009

WASHINGTON — In a major setback for business groups that had hoped to build a barrier against injury lawsuits seeking billions of dollars, the Supreme Court on Wednesday said state juries may award damages for harm from unsafe drugs even though their manufacturers had satisfied federal regulators.

The ruling could have significant implications beyond drug manufacturing. Many companies have sought tighter federal regulation in recent years in part to shield themselves from litigation.

The court, by a 6-to-3 vote, upheld a jury verdict of $6.7 million in favor of a musician from Vermont whose arm had to be amputated after she was injected with an anti-nausea drug. The drug’s manufacturer, Wyeth, had argued that its compliance with the Food and Drug Administration’s labeling requirements should immunize it from lawsuits.

Pharmaceutical companies were especially disappointed by Wednesday’s decision.

Ronald Rogers, a spokesman for Merck, said, “We believe state courts should not be second-guessing the doctors and scientists at the F.D.A.”

Merck was hit with several huge damage awards over its painkiller Vioxx before agreeing to a $4.85 billion settlement in 2007. Allowing juries to make determinations about drug risks, Mr. Rogers said, would cause “mass confusion.”

The Supreme Court has been sympathetic in recent years to arguments that federal law should pre-empt state injury suits. Last year, in Riegel v. Medtronic, an eight-justice majority of the court ruled that many state suits concerning injuries caused by medical devices were barred by the express language in a federal law. Wednesday’s decision addressed implied pre-emption, a different legal standard.

Drug companies and other businesses, supported by the Bush administration, had hoped the Vermont case would establish broader protections. They relied not on express language in a statute enacted by Congress, as in Riegel, but on what might be implied from federal regulatory standards and policies — in this case, from the drug agency’s authority to approve drug labels.

Producers of goods as different as antifreeze, fireworks, popcorn, cigarettes and light bulbs have sought to take refuge behind federal oversight in recent years to fend off litigation. After Wednesday’s decision, those efforts are most likely to succeed if they are based on express language in a Congressional statute or a specific regulatory action that makes compliance with state requirements impossible.

“This narrows the playing field,” for implied pre-emption arguments, Mark Herrmann, a corporate defense lawyer in Chicago, said of the decision. “This does not eliminate the playing field.”

Most drug company stocks, including Wyeth’s, closed up on Wednesday, as did the Dow Jones industrial average, which rose 150 points, breaking a long losing streak.

Catherine M. Sharkey, a law professor at New York University, said the decision does mean that “there is certainly a thumb on the scale against the more aggressive arguments for implied pre-emption.”

Justice John Paul Stevens, writing for the majority in Wednesday’s decision, Wyeth v. Levine, No. 06-1249, said Congress could have required pre-emption in the case but had not. “Evidently,” he said, “it determined that widely available state rights of action provided appropriate relief for injured consumers.”

Justice Stevens noted that Congress did adopt just such an express pre-emption provision for medical devices in the law at issue in the Riegel case.

Until a recent change in policy under the Bush administration, Justice Stevens wrote, the drug agency had welcomed state injury suits as a useful complement to federal regulation. But in “a dramatic change in position” in 2006, Justice Stevens said, the agency reversed that longstanding policy not withstanding its “limited resources to monitor the 11,000 drugs on the market.”

The agency’s new position, Justice Stevens wrote, “is entitled to no weight.” He was similarly dismissive of a brief supporting Wyeth filed by the Justice Department under former President George W. Bush, saying it was “undeserving of deference.”

Justice Stevens was joined by Justices Anthony M. Kennedy, David H. Souter, Ruth Bader Ginsburg and Stephen G. Breyer. Justice Clarence Thomas voted with the majority but did not adopt Justice Stevens’s reasoning, saying instead that he objected generally to “far-reaching implied pre-emption doctrines” that “wander far from the statutory text.”

Justice Samuel A. Alito Jr., writing for the three dissenters, said the court had done an about-face, “turning yesterday’s dissent into today’s majority opinion” and turning ordinary injury suits into a “frontal assault on the F.D.A.’s regulatory regime for drug labeling.”

“This case illustrates,” Justice Alito said, “that tragic facts make bad law.”

The case began in 2000, when Diana Levine, suffering from migraine headaches, visited a clinic. She was given injections of Demerol for the pain and Wyeth’s drug Phenergan for nausea.

If Phenergan is exposed to arterial blood, it can cause swift and irreversible gangrene. For that reason, it is usually administered by intramuscular injection or intravenous drip. This time, a physician’s assistant used a third method, injecting the drug into what she thought was a vein, a method known as “IV push.”

In the following weeks, Ms. Levine’s hand and forearm turned black, and they were amputated in two stages. She settled a lawsuit against the clinic and went to trial against Wyeth, claiming its warnings against IV-push administration were not strong enough.

She greeted Wednesday’s decision with elation. “Next to getting my hand back,” she said of the Supreme Court, “it’s the least they could have done and the best they could have done.”

Bert Rein, a lawyer for Wyeth, said the company had “fully complied with federal law in its labeling of Phenergan,” adding that the F.D.A. is “in the best position to weigh the risks and benefits of a medicine.”

Justice Alito said Wyeth had provided ample notice about the risk of gangrene in “six separate warnings,” some of them “in boldfaced font and all-capital letters,” on the drug label the F.D.A. had approved.

Justice Alito, writing for himself, Chief Justice John G. Roberts and Justice Antonin Scalia, added that juries see only the “tragic accident” before them and “are ill-equipped to perform the F.D.A.’s cost-benefit-balancing function.” The agency, by contrast, he wrote, “has the benefit of the long view” and “conveys its warnings with one voice.”

“After today’s ruling,” he said, “parochialism may prevail.”

Click here to download a PDF of the actual Supreme Court Opinion in its entirety.

©2009 Angel Reyes
www.ReyesLaw.com

Pain Drugs to Get New Restrictions
FEBRUARY 9, 2009, 10:34 P.M. ET
By JENNIFER CORBETT DOOREN

The Food and Drug Administration said Monday it will subject the makers of certain extended-release pain drugs to a new risk-management program designed to cut down on misuse and abuse of the products. New government figures show a rise in non-medical use of prescription pain drugs among adults.

Opioid drugs formulated in extended-release versions of OxyContin, morphine and fentanyl patches are meant for round-the-clock pain management for patients with cancer and other chronic conditions.

Misuse and Abuse
FDA officials have said they've seen reports of inappropriate prescribing by doctors amid the increase in misuse and abuse, both intentional and unintentional, of the products since the drugs were first approved in the mid-1990s.

Active ingredients in the drugs are designed to treat pain for an extended time, such as 12 hours. Drug abusers can tamper with such products and get all the effects of a drug at once, creating a heroin-like high.

"We continue to see reports of an ankle sprain and [patients] are given a fentanyl patch," said John Jenkins, the director of the FDA's office of new drugs. He said a major part of the new program will be efforts to educate doctors about appropriate prescribing of the products. "This obviously is going to be the largest risk-management program we've undertaken," he said.

Although Mr. Jenkins and other agency officials wouldn't speculate about what the final risk-mitigation program would look like, it could have elements of a program designed to limit the use of the acne drug isotretinion (commonly known by the brand name Accutane) by women of child-bearing age because the product causes birth defects. That program requires doctors, pharmacists and patients to register and meet certain requirements in order to get a new prescription each month.

The agency sent letters to 16 manufacturers of 24 products including Purdue Pharma LP, the maker of OxyContin, which is available in an extended-release form; a unit of Johnson & Johnson that makes a fentanyl patch; and King Pharmaceuticals Inc., the maker of an extended-release form of morphine. The letters told the drug makers of agency plans to require a risk-evaluation and -mitigation strategy, or REMS, "to ensure that the benefits of the drugs continue to outweigh the risks."

Getting Input
The FDA said it would meet with the drug manufacturers next month to talk about developing a REMS and would then meet with other federal agencies, patient and consumer-advocacy groups and health-care professionals to get additional input in the coming months.

There will be no immediate changes for prescribers or users of extended-release pain pills. An estimated 21 million prescriptions for extended-release opioids were prescribed for 3.7 million patients in 2007, Mr. Jenkins said. Other pain pills that are immediate-release and more commonly prescribed for pain won't be affected.

The agency noted that previous efforts to cut down on abuse and misuse of extended-release products, such as putting additional warnings on products labels, haven't really worked.

"Despite these efforts, the rates of misuse and abuse, and of accidental overdose of opioids, have risen over the past decade," the agency said in a statement posted on its Web site. "The FDA believes that establishing a REMS for opioids will reduce these risks, while still ensuring that patients with legitimate need for these drugs will continue to have appropriate access."

The FDA can mandate the elements of a risk-management plan as part of legislation that took effect last year. Mr. Jenkins said that authority should make the new effort to cut down on abuse and misuse more effective than previous plans.

Write to Jennifer Corbett Dooren at jennifer.corbett-dooren@dowjones.com

©2009 Angel Reyes
www.ReyesLaw.com

Panel Urges Darvon Ban
WASHINGTON -- A Food and Drug Administration panel recommended banning the painkiller Darvon and a related drug, following a decades-long effort by critics who charged that the drugs' users often intentionally or unintentionally overdose on them.

Darvon has been on the market since 1957, and Saturday marks the 30th anniversary of the first congressional hearing on its safety. Nonethless, it still enjoys wide use in treating mild to moderate pain. More than 20 million prescriptions were written in 2007 for products containing propoxyphene, the active ingredient in Darvon, according to the FDA.

The panel voted 14-to-12 that the drug's benefits didn't outweigh its risks, and called for removal from the U.S. market. The final decision is up to the FDA, which usually adopts panel recommendations but not always, especially when the vote is so close.

Darvon's defenders argue it is safe and effective when used as directed. The label warns against taking it in combination with alcohol or certain other drugs.

Darvon was developed by Eli Lilly & Co., which later combined propoxyphene with acetaminophen, the active ingredient in Tylenol, and sold that pill as Darvocet. Today the drugs are marketed by generic-drug makers.

Sidney Wolfe, a doctor at the advocacy group Public Citizen, has been fighting Darvon since the late 1970s, and triggered Friday's panel meeting with a petition and a lawsuit that sought to force the FDA to ban the drug.

In its petition, Public Citizen cited data from the Drug Abuse Warning Network implicating propoxyphene in 5.6% of drug-related deaths from 1981 to 1999. Public Citizen also said the network reported 2,110 accidental deaths related to propoxyphene over the same period.

The FDA also cited reports of serious events such as suicides, intentional and unintentional overdoses and heart attacks. But the agency's analysts said the evidence wasn't conclusive enough to ban Darvon.

In an interview about Darvon before Friday's meeting, Dr. Wolfe said, "Claims of its efficacy have been seriously undercut by the FDA's own analysis." He noted that the agency said Darvon "possesses weak analgesic effects."

In his presentation Friday, Dr. Wolfe presented updated data showing 503 deaths in 2007 in which propoxyphene was listed as a contributing factor. "All drugs have risks," Dr. Wolfe said. "If they don't have benefits they need to come off the market."

Write to Jennifer Corbett Dooren at jennifer.corbett-dooren@dowjones.com and Alicia Mundy at alicia.mundy@wsj.com

©2009 Angel Reyes
www.ReyesLaw.com

©2008 Angel Reyes
www.ReyesLaw.com

Doctors Claim Glaxo Dismissed Worries on Avandia
NOVEMBER 19, 2008
By ALICIA MUNDY
Drug Maker Tried to Make Physician at Maryland Hospital Stop Talking About Concerns; Company Defends Its Effort

HAGERSTOWN, Md. -- Last year, after news broke that the diabetes drug Avandia was linked to a high risk of heart attacks, reports that the drug's maker had tried to stifle safety questions from a prominent Duke University researcher years earlier provoked a furor.

Now it turns out that the Duke researcher wasn't alone in suggesting a tie to heart problems. A doctor from a small Maryland hospital linked Avandia to congestive heart failure in 2000, but the drug's maker, GlaxoSmithKline PLC, rejected her warning and tried to make her stop talking about it with other doctors and hospitals, according to documents and interviews. Glaxo defends its effort, which it says was an attempt to correct "inaccuracies." The head of the doctor's hospital says he ignored Glaxo's overture.

Internist Mary Money of Hagerstown, Md., said in an interview that she first noticed problems with Avandia shortly after it came on the market in the summer of 1999. When she and a colleague began to raise concerns, Dr. Money said, the company dismissed their concerns. The Food and Drug Administration was unresponsive, the doctors say.

The Senate and House in 2007 began looking at whether Glaxo suppressed information and threatened the Duke researcher, charges that Glaxo has denied. Now the Senate probe, led by Chuck Grassley of Iowa, is investigating whether Glaxo's efforts to defend Avandia's safety led to intimidation against other doctors who were suggesting possible links to cardiac dangers. Mr. Grassley, the ranking Republican on the Finance Committee, has demanded documents from Glaxo and is expected to release a detailed report on Avandia soon, according to staffers.

Earlier in 2007, a study in the New England Journal of Medicine reported that Avandia could raise the risk of heart attack by 43%. The FDA called for a black-box warning on the drug's label about the risk of congestive heart failure and heart attack.

Dr. Money talked recently about a patient who came to her in 1999 with congestive heart failure. "That fall, I had a woman patient with massive fluid overload and such shortness of breath that she had to sit up at night," she said.

The patient had begun taking Avandia two weeks earlier, and an echocardiogram showed high pressure in the arteries of the lungs. Dr. Money said she took the patient off the drug, and within a few days the symptoms almost disappeared.

In the next few months, Dr. Money and the head of the hospital's diabetes center, Stephen Lippman, found other patients who had similar symtoms.

Dr. Money alerted SmithKline Beecham, the name of the drug maker before a 2001 merger. The company met with her and Dr. Lippman at Washington County Hospital in Hagerstown in April 2000.

The two doctors presented data on 85 of their patients who had used Avandia, according to documents from the meeting. More than half of the patients had significant edema, or swelling, and about half of that group also had high pulmonary pressure and shortness of breath. Three had been hospitalized for congestive heart failure.

The meeting was a waste of time, Dr. Money said. "They came to tell us how wrong we were, not to listen," she said.

Meanwhile, a company consultant who called into the meeting from the University of Pennsylvania dismissed the Hagerstown doctors' echocardiograms as too poor to show anything useful.

"They suggested we were country bumpkins, and practically said, 'Don't worry your pretty heads. We have smarter people than you looking at this, and there's no problem,'" recalled Dr. Lippman, a physician who also holds a doctorate in molecular biology.

A GlaxoSmithKline spokeswoman, Mary Ann Rhyne, said Dr. Money's theories were "unsubstantiated" and she was misinterpreting journal articles to support her case.

The next month, two SmithKline executives wrote to the hospital's chief of staff, calling on him to stop Dr. Money from talking about her concerns to other hospital doctors.

"[W]e respectfully ask that your hospital not involve itself in the dissemination of information which has not been substantially verified, and that you take immediate steps to stop the dissemination of this unsubstantiated information to your medical staff," said the letter, signed by two SmithKline executives, which was viewed by The Wall Street Journal.

GlaxoSmithKline's Ms. Rhyne said the letter was justified. "When GSK learns about statements by physicians that are inconsistent with the scientific data on its medicines, it has the responsibility to do what it can to correct these inaccuracies," she said.

The hospital's then chief of staff, Salvatore DiMercurio, said he decided to ignore the letter after consulting the hospital's executive committee. "It came down to whom do you trust -- a doctor you know and have worked with, or the people who are threatening you?" Dr. DiMercurio said.

Dr. Money also contacted the FDA, but she received only a form letter in response. The FDA didn't respond to requests for comment.

Drs. Money and Lippman said they found themselves at an impasse after the company and the FDA failed to listen to their concerns. Meanwhile, Dr. Lippman took a job in California.

Dr. Money said she continued to discourage the use of Avandia when speaking to colleagues. But she didn't seek broader attention until last year, when she read about the Duke researcher, John Buse, and Glaxo's reponse when he raised questions about Avandia.

In testimony to the House in 2007, Dr. Buse said he was characterized as a "liar" and threatened with a lawsuit if SmithKline's stock dropped because of his statements about Avandia's possible dangers.

Glaxo upgraded the warnings on Avandia's label more than a dozen times between 1999 and the 2007 black box, the strongest level of warning. One change, in 2001, said the drug could lead to excessive edema, which in turn could lead to congestive heart failure.

The changes got relatively little notice, and Avandia reached peak world-wide sales in 2006 of $2.5 billion.

In May 2007, after the New England Journal of Medicine reported the high risk of heart attack linked to the drug, officials in the FDA's safety division recommended the drug be pulled from the market.

An outside advisory committee disagreed, but sales since then have plunged. In the first three quarters of this year, Avandia sales were $856.7 million, down 45% from a year earlier, according to the company.

The American Diabetes Association and its European counterpart told doctors last month not to use the drug, though it remains on the market.

In addition to the Senate probe over Avandia, GlaxoSmithKline has been under investigation by the Senate over the safety of its antidepressant Paxil. The Justice Department is also investigating the company over marketing issues, the company has said, and a grand jury in Boston has asked witnesses about Paxil's safety, according to the witnesses.

It isn't clear whether Avandia is also part of that investigation. The Justice Department declined to comment.

—-- Louise Radnofsky contributed to this article.

Write to Alicia Mundy at alicia.mundy@wsj.com
 

My firm was the first to win a federal case against the makers of any fentanyl pain patch.  The jury awarded the family of 28-year-old Adam Hendelson $5.5 million last year in a West Palm Beach federal court.

Please see the Bloomberg.com article below:

J&J Pain Patch Gave Woman Fatal Dose, Lawyer Tells Chicago Jury
Bloomberg.com
Trials/Appeals
October 30, 2008

A Johnson & Johnson unit's defective pain-killing patch delivered a fatal overdose to a 38-year-old woman, her family's attorney told a Chicago jury at the start of a wrongful-death trial.

Janice DiCosolo, a mother of three from Cicero, Illinois, died in February 2004 from toxic effects of the drug fentanyl, the active ingredient in the Duragesic trans-dermal patch made by Alza Corp. and distributed by Janssen Pharmaceutica Products, according to a complaint filed by her husband, John.

"Each patch has enough fentanyl in it to kill 10 300-pound men," John DiCosolo's attorney, Jim Orr, told a Chicago state court jury of seven men and seven women in his opening statement yesterday. Orr asked the jury to award $25 million to the DiCosolo family.

The patches generated $1.16 billion in sales last year for Johnson & Johnson, the world's largest maker of medical devices. The DiCosolo trial began a day after a Florida jury awarded more than $13 million to the family of Susan Hodgemire, a 34-year-old mother of five who died after using a Duragesic patch in 2002.

Fentanyl is a pain killer that is 100 times more powerful than morphine, according to Orr, an attorney in the Dallas firm of Heygood, Orr, Reyes & Bartolomei. Janice DiCosolo was found wearing one of the patches when she died. Her husband's lawyers said the product was defectively made and that Alza and Janssen should be held strictly liable for her death.

The specific patch blamed for DiCosolo's death wasn't defective, attorneys for the units said in a July 30 court filing. The elevated levels of fentanyl found in her bloodstream in a post-mortem examination flowed from her organs after she died and weren't from the patch, they said.

Janssen recalled one Duragesic lot in February 2004, one day after DiCosolo died, because of improper sealing, defense lawyer David Sudzus wrote in that filing. The patch worn by DiCosolo was from that lot, he said.

The case is DiCosolo v. Janssen Pharmaceutica, 04L5351, Cook County, Illinois Circuit Court, Law Division (Chicago).

©2008 Angel Reyes
www.ReyesLaw.com

The manufacturer of the Duragesic Transdermal Pain Patch and other brands are being sued due to a leak in the patch that allows too much of the opioid painkiller to enter the system directly through the skin, causing fatal overdose.  Fentanyl is 100 times stronger than morphine, and this lethal drug has now killed several victims.

Jury awards $13.3M to family in pain-patch death
Orlando Sentinel
Rene Stutzman | Sentinel Staff Writer
October 30, 2008

A Sanford jury has awarded $13.3 million to the family of a woman who died when her pain patch failed, flooding her system with too much medicine.

Dozens of other suits have been filed nationally against drug giant Johnson & Johnson, alleging that its patches leaked and killed patients. But this week's judgment in Seminole Circuit Court was the biggest to date.

Susan Diane Hodgemire, 34, who lived near Apopka with her husband and five children, died June 8, 2002, a few days after she underwent back surgery.

She had placed two patches containing fentanyl, a powerful pain reliever, on her right arm as directed, attorney Joseph Taraska said. But the gel pack inside one or both patches began to leak, Taraska said, allowing the medicine to come into direct contact with her skin, where it was absorbed too quickly.

The patches, he said, are designed to release medicine over a 72-hour period.

In the middle of the night, Hodgemire began to vomit violently, lapsed into a coma, stopped breathing and died.

Jurors deliberated six hours before returning their verdict about 10:30 p.m. Tuesday. They blamed the woman's death on two Johnson & Johnson companies: patch manufacturer ALZA Corp. of Vacaville, Calif., and distributor Janssen LP of Titusville, N.J. They were ordered to pay 80 percent of the judgment.

The remainder is to be paid by Kurt Wood, a former physician assistant at Jewett Orthopaedic Clinic. The jury found him guilty of malpractice. When Hodgemire phoned for help in the middle of the night, Wood told her to take anti-nausea medicine and go back to bed, Taraska said.

Wood's lawyer, Aram Megerian, said Hodgemire failed to tell the physician assistant how ill she was when she called.

Jewett was originally named in the suit, but Taraska said the case had been "resolved."

The patient's husband, Scott Hodgemire, said Wednesday that he was wowed by the judgment but is prepared to fight an appeal.

"The only real point here is there's a bunch of children who lost their mother. One doesn't even know his mother," Hodgemire said. That's a reference to the couple's youngest son, who was 2 at the time of her death. "No amount of money, no amount of litigation is ever going to bring her back."

Taraska said ALZA knew it was producing defective patches but kept doing so.

The brand of patch Hodgemire was wearing -- Duragesic -- has been recalled four times, said Greg Panico, a Janssen spokesman. The most recent recall, in February, was because of cuts found in the patch's drug reservoir, he said.

"We sympathize with the Hodgemire family over their loss," he said, "however, we disagree with the jury's verdict and are considering our options for an appeal."

Hours after the Sanford jury returned its verdict, attorneys for a Chicago-area woman who died in 2004 began presenting their case against ALZA and Janssen to an Illinois jury.

Janice Dicosolo, a mother of three, died of a fentanyl overdose after wearing a Duragesic patch, said Eric Pearson, a Dallas lawyer whose firm represents her family.

It's the same firm that won a $5.5 million judgment against ALZA and Janssen in a West Palm Beach federal court last year in the death of Adam Hendelson, 28. He died in 2003 from a fentanyl overdose.

In 2006, a Houston jury awarded the family of another overdose victim more than $700,000.

Johnson & Johnson is fighting dozens of other pain-patch cases in courts across the country.

©2008 Angel Reyes
www.ReyesLaw.com

FDA Warns Bayer on Two Aspirin Products
Wall Street Journal
 
WASHINGTON -- Pharmaceutical giant Bayer AG has received warnings from federal regulators for illegally marketing two unapproved over-the-counter medicines combining aspirin with dietary supplements.

Bayer's "Bayer Aspirin With Heart Advantage" and "Bayer Women's Low Dose Aspirin + Calcium" are drugs and require Food and Drug Administration approval before being marketed, the FDA said in two letters posted on its Web site Tuesday. The letters are dated Monday.

The two drugs combine Aspirin with over-the-counter dietary supplements. Bayer's Women's combines Aspirin with calcium. Bayer Aspirin with Heart Advantage combines Aspirin with phytosterols, which Bayer says help lower cholesterol.

Products that combine drugs and dietary supplements require FDA approval before they can be marketed, even if the drug, in this case Aspirin, is already approved.

Bayer has been marketing Aspirin Heart Advantage since earlier this year, while Bayer Women's Low Dose Aspirin + Calcium has been on the market since 2002. A company spokeswoman said Bayer was in the process of reviewing the FDA letters and will respond to the agency.

She said Bayer stands behind "both products and all the marketing claims that we make in their support."

Bayer has faced criticism from lawmakers over television ads for Bayer with Heart Advantage. Earlier this month, leaders of the House Energy and Commerce Committee said Bayer appeared to be ignoring FDA recommendations that companies refrain from marketing products that combine drugs and dietary supplements.

The FDA doesn't closely scrutinize dietary supplements for safety and effectiveness, and lawmakers are concerned that a product containing an FDA-approved drug and a supplement misleads people to believe the supplement has also been vetted.

"The marketing of these unapproved drugs is troubling," said Janet Woodcock, who heads the FDA's drug and research center, in a statement. "The overuse or misuse of these aspirin-containing products can put consumers at risk for internal bleeding and other adverse events."

The FDA says, however, it isn't aware of any significant adverse events associated with the drugs.

Bayer with Heart Advantage is marketed to help treat heart disease, and Bayer Women's is marketed to treat osteoporosis. Because the drugs purport to treat a disease, they should be taken under the diagnosis and supervision of a health care professional, which is impossible for a drug that can be bought without a prescription, the FDA said.

Furthermore, the FDA said the labels for the drugs send a "mixed message about the products' purposes and the length of time for which the products can be safely used."

Write to Jared A. Favole at jared.favole@dowjones.com

©2008 Angel Reyes
www.ReyesLaw.com

Researchers: Merck Vioxx study was for marketing
By LINDA A. JOHNSON, AP
posted: 26 MINUTES AGO

TRENTON, N.J. -A 1999 Merck  & Co. study of its since-withdrawn painkiller Vioxx, touted to participating doctors and patients as meant to show whether Vioxx caused fewer stomach problems than another drug, was primarily a stealth marketing strategy, researchers report.

The true purpose was to get lots of doctors and patients in the habit of using Vioxx just in time for its launch, according to doctors who uncovered internal Merck memos discussing the strategy behind the study, called ADVANTAGE. They did so while reviewing roughly a million Merck documents for plaintiffs' lawyers preparing for trials in Vioxx lawsuits.

Drug companies are widely suspected of doing many such "seeding," or marketing studies, but there's been no "smoking gun" proving it before, according to the Annals of Internal Medicine, which published Merck's original report on ADVANTAGE in 2003 and will publish the new report Tuesday.

An accompanying editorial, co-authored by Annals editor Dr. Harold C. Sox, states the journal was not told the true purpose of ADVANTAGE, which compared Vioxx with an older, cheaper pain reliever, naproxen, when it published results indicating Vioxx was better tolerated.

Dr. Jonathan Edelman, head of scientific affairs at Merck Research Laboratories, said Monday "the ADVANTAGE study was primarily a scientific study" designed and executed by the company's clinical research unit and that any later use of data for marketing was a separate operation.

But Dr. Kevin P. Hill said he and colleagues, while working as paid consultants for lawyers representing plaintiffs who claimed Vioxx caused heart attacks or other harm, stumbled on documents indicating Merck's marketing division designed ADVANTAGE and handled the data collection and analysis.

Using funding from the Robert Wood Johnson Foundation's clinical scholars program, they searched further, uncovering items such as a memo from two top Merck executives nominating the study for an internal marketing award. "The objectives were to provide product trial among a key physician group to accelerate uptake of Vioxx as the second entrant in a highly competitive new class," the memo states.

ADVANTAGE used about 600 family doctors new to clinical research, with each getting a stipend plus fees for recruiting a handful of patients each. Most clinical trials are run by a limited number of specialists at major teaching hospitals that each recruit hundreds of patients.

Vioxx came on the market in June 1999, after rival Pfizer Inc.'s Celebrex. Both makers claimed their drug caused less cramping, diarrhea and dangerous gastrointestinal bleeding than other pain relievers. Merck battled hard for market share, and Vioxx at its peak brought in about $2.5 billion a year.

Hill, now a staff psychiatrist at McLean Hospital in Massachusetts, said he and his colleagues found documents indicating "ADVANTAGE was marketing framed as scientific research," with an emphasis on how much Vioxx doctors in the study later prescribed.  "I don't think people would be willing to (risk side effects) if they knew that the aim of a clinical trial was to boost profits for a pharmaceutical company," Hill said. The study's name implied it had a scientific purpose: ADVANTAGE, or Assessment of Differences between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness.

But Hill said doctors participating in ADVANTAGE got a kit telling them how to talk to other doctors about Vioxx, and another Merck study running at the same time, called VIGOR, also examined how safe Vioxx was for people with gastrointestinal problems, so ADVANTAGE wasn't needed. VIGOR's results were
published in 2000.

Merck spokesman Ron Rogers said Hill and his colleagues have been critics of Merck and just cherrypicked "some documents to support their thesis."

Dr. Bruce Psaty, a University of Washington epidemiologist, said Hill and his colleagues had disclosed their conflict of interest in their report but that the ADVANTAGE trial wasn't transparent about its purpose.

"I would think that at some level this is standard practice," he said of seeding studies, but they don't come to light except during the discovery phase of litigation. Dr. Ross McKinney, director of Duke University's bioethics center, said seeding studies have been around for decades and usually are called postmarketing studies, meaning they're for drugs approved for sale. He said most never get published, but this one did because it addressed an important scientific question, stomach tolerability, even though it was a seeding trial. But McKinney said seeding studies make the public skeptical about enrolling in clinical studies.

"It's a serious violation of research ethics" and prevents patients from figuring out the risks and benefits of participating in the study, said Arthur Caplan, who heads University of Pennsylvania's medical ethics department. Whitehouse Station, N.J.-based Merck pulled Vioxx off the market on Sept. 30, 2004, after its own research showed the then-blockbuster arthritis treatment doubled risk of heart attack and stroke. It has since reached a $4.85 billion settlement to end the bulk of personal injury suits over Vioxx, and the first payment checks are slated to go out later this month.

Sox, the Annals editor, and Dr. Drummond Rennie, the Journal of the American Medical Association's deputy editor, wrote that the institutional review boards required to protect patients in clinical studies should ask whether an experiment is a seeding study, particularly when there are obvious clues.

"Simply shining a bright light on their existence may have already sown the seeds of their destruction," they write.
 

Home deaths from drug errors soar
CHICAGO, Illinois (AP) -- Deaths from medication mistakes at home, such as actor Heath Ledger's accidental overdose, rose dramatically during the past two decades, an analysis of U.S. death certificates finds.

The authors blame soaring home use of prescription painkillers and other potent drugs, which 25 years ago were given mainly inside hospitals.

"The amount of medical supervision is going down and the amount of responsibility put on the patient's shoulders is going up," said lead author David P. Phillips of the University of California, San Diego.

The findings, based on nearly 50 million U.S. death certificates, are published in Monday's Archives of Internal Medicine. Of those, more than 224,000 involved fatal medication errors, including overdoses and mixing prescription drugs with alcohol or street drugs.

Deaths from medication mistakes at home increased from 1,132 deaths in 1983 to 12,426 in 2004. Adjusted for population growth, that amounts to an increase of more than 700 percent during that time.

In contrast, there was only a 5 percent increase in fatal medication errors away from home, including hospitals, and not involving alcohol or street drugs.

Abuse of prescription drugs plays a role, but it's unclear how much. Valid prescriptions taken in error, especially narcotics such as methadone and oxycodone, account for a growing number of deaths, said experts who reviewed the study.
The increases coincided with changing attitudes about painkillers among doctors who now regard pain management as a key to healing. Multiple prescription drugs taken at once -- like the sleeping pills, painkillers and anxiety drugs that killed "Dark Knight" star Ledger -- also play a part, experts said.

"When we see overdoses, we're seeing many more mixed drug overdoses," said Dr. Jeffrey Jentzen, president of the National Association of Medical Examiners and director of autopsies at the University of Michigan in Ann Arbor. Jentzen said autopsies are much more likely to include toxicology tests today than 25 years ago, which would contribute to finding more fatal medication errors as cause of death.

But Phillips said there were no significant increases in other poisonings, such as suicidal overdoses or homicides, so more testing doesn't explain the huge increase. The analysis excluded suicides, homicides and deaths related to side effects.

The increase was steepest in death rates from mixing medicine with alcohol or street drugs at home; that death rate climbed from 0.04 per 100,000 people in 1983 to 1.29 per 100,000 people in 2004.

Many patients ignore the risk of mixing alcohol with prescriptions, said Cynthia Kuhn of Duke University Medical Center, who was not involved in the study.

"They think, 'Oh, one drink won't hurt.' Then they have three or four," Kuhn said.

The increase in deaths was highest among baby boomers, people in their 40s and 50s.

"We're sort of drug happy," said boomer Dr. J. Lyle Bootman, the University of Arizona's pharmacy dean, who was not involved in the research. "We have this general attitude that drugs can fix everything."

People share prescriptions at an alarming rate, Bootman said. One recent study found 23 percent of people say they have loaned their prescription medicine to someone else and 27 percent say they have borrowed someone else's prescription drugs.

Kenneth Kolosh, a statistics expert at the National Safety Council, praised the study but said improved attention to coding location on death certificates may account, in part, for the huge increases the researchers found.

Phillips countered that home deaths from any cause increased relatively little during the time period, so better coding doesn't explain the change.

Michael R. Cohen, president of the Institute for Safe Medication Practices, said more states should require pharmacists to teach patients about dangerous drugs and insurers should pay pharmacists to do so.