The Bitter Pill

The Official Blog of UNITE – uniteforlife.org

Novartis Failed to Warn About Elidel Cancer Link

Evelyn Pringle December 28, 2006

Most lawsuits in which drug makers have tried to use preemption to dismiss failure-to-warn claims have been against companies accused of failing to warn about the risk of suicide associated with antidepressants known as selective serotonin inhibitors or SSRIs.

However, a case in Pennsylvania against Novartis, involves a toddler who developed cancer due to a failure-to-warn about the risks associated with the topical drug Elidel. In an important decision sure to have an impact on many other cases in the US, on October 16, 2006, a US District Court in Eastern Pennsylvania refused to grant the drug maker’s preemption motion in, Perry v Novartis Pharma Corp, — F Supp 2d —, 2006 WL 2979388.

Elidel was approved by the FDA on December 13, 2001, to treat atopic dermatitis, commonly known as eczema, in a cream applied directly to the skin, for persons over the age of two.

Elidel belongs to a class of immunosuppressant drugs known as calcineurin inhibitors. At the time of its approval, there were already concerns about an association between Elidel and cancer because other calcineurin inhibitors that were used to treat organ transplant patients were known to increase the risk of cancer and lymphoma, and carried a Black Box warning to that affect.

At the time of its approval, Elidel had also been found to increase the risk of cancer in animals when administered at high doses.

Because of its concerns about cancer, the FDA placed restrictions on Elidel and approved it only for short-term and intermittent use, and as a second-line of treatment to be used only when traditional therapies such as corticosteroids were found to be ineffective.

Following FDA approval, Novartis aggressively promoted Elidel, and as a result millions of prescriptions were written, many of which were off-label, meaning outside the approved indications and limitations specified on the label.

In the case of young Andreas Perry, the prescription was off-label in that no other treatment had been tried for his eczema prior to prescribing Elidel. Six months after he began using the cream, in October 2003, Andreas was diagnosed with lymphoblastic lymphoma, a form of cancer.

Although his eczema was annoying and uncomfortable, it was not life-threatening and his parents never considered for a moment that Andreas would develop cancer from a medicated cream prescribed for a toddler who was barely 2-years-old.

But on the other hand, Novartis can hardly claim ignorance about the link between cancer and Elidel because when the reports of cancer started coming in, the FDA began openly discussing the need to strengthen the warnings and the fact that the drug was being over-prescribed off-label to children for unapproved uses.

In October, 2003, the FDA’s Pediatric Advisory Subcommittee to the Anti-Infective Drugs Advisory Committee met to evaluate the cancer rates among pediatric patients treated with calcineurin inhibitors and discussed the possibility of changing the label to specifically warn against their use in patients under two.

At the hearing, a pharmacist and safety evaluator reported that more than 3.2 million prescriptions for Elidel had been dispensed by August 2003, with 17% of those prescriptions written “off-label” for children under the age of 2, and representing 22% of the adverse event reports for the drug.

On February 15, 2005, the Committee met again amidst even more reports of off-label use of calcineurin inhibitors with children which caused concern for many members of the Committee. The briefing memorandum for the meeting reported that more than 500,000 prescriptions had been written for children under 2 during a one year period between June 2003 and May 2004.

At this meeting, the panel voted to recommend that a “Black Box” warning be added to the label about the increased risk of cancer associated with the topical use of the two calcineurin inhibitors, Elidel and Protopic, and also about the lack of long-term safety data on the drugs.

The FDA issued a public health alert on March 10, 2005, stating in part, “Animal studies have shown that three different species of animals developed cancer following exposure to these drugs applied topically or given by mouth, including mice, rats and a recent study of monkeys.”

“Based on the advice of the FDA Pediatric Advisory Committee, which met on February 15, 2005,” the alert advised, “FDA will require labeling changes for Elidel and Protopic, including the placement of a boxed warning about the potential cancer risk.”

However, this case illustrates another situation like Vioxx and the SSRIs, where the FDA is as much to blame as Novartis for patients being injured after the danger was known, because the agency knew that a “Black Box” warning should be added immediately but allowed the drug company to dilly-dally around for nearly a year before adding the cancer warning on January 19, 2006.

In their lawsuit, the Perrys allege that despite Novartis’s knowledge of the association between Elidel and cancer, Novartis promoted it as safe for the treatment of eczema. It also alleges that the drug was advertised, marketed, and promoted as safer than traditional corticosteroid treatments, in conscious disregard of the limitations that the FDA placed on its approval, and that these actions contributed to the inadequacy of the warnings.

In response, Novartis filed a motion to dismiss the failure-to-warn claims based on the FDA’s new preemption policy. On January 18, 2006, the FDA issued new regulations regarding the labeling of prescription drugs, supposedly to provide doctors and patients with clearer information. However, in the preamble to the new rules, the FDA inserted the claim that State tort lawsuits alleging a failure-to-warn about risks associated with drugs approved by the FDA are preempted by federal law.

After failing at efforts to implement tort reform, this move is largely seen as the Bush administration’s last ditch attempt to immunize the pharmaceutical industry with policies written by politically appointed officials carefully planted at the top of the nation’s regulatory agencies.

Right from the start, it should be noted that State failure-to-warn lawsuits against drug companies have existed for over a century. Back in 1852, in the New York case of, Thomas v Winchester, 1852 WL 4748, the court stated, “A dealer in drugs and medicines, who carelessly labels a deadly poison as a harmless medicine, and sends it so labeled into market, is liable to all persons, who, without fault on their part, are injured by using it as such medicine in consequence of the false label.”

Second, if Congress wanted to preempt State tort claims it would have done so. Congress was fully aware of these lawsuits in 1934, when it enacted the Food, Drug and Cosmetic Act, and chose not to include a private right of action for damages in the Act after determining it was “unnecessary,” because a “common-law right of action exists.”

For as former Chief Counsel of the FDA, Margaret Porter, wrote in 1997, “FDA product approval and state tort liability usually operate independently, each providing a significant, yet distinct, layer of consumer protection.” The Lohr Decision: FDA Perspective and Position, 52 Food & Drug. L.J. 7, 11 (1997).

While it may be true that the FDA approves a drug’s label when it approves the drug, the label is not fixed in stone. It is well known that drugs are approved based on very limited clinical trials and understood that there is a strong likelihood that new risks will be identified as a drug is widely prescribed in the general population.

For this reason, under federal regulations, a drug maker’s duty to provide warnings to health care professionals and consumers continues as long as a drug is on the market. In its own regulations, the FDA itself has noted that labeling does not always contain the most current information because “advances in medical knowledge and practice inevitably precede formal submission of proposed new labeling by the manufacturer and approval by the FDA.”

And that’s why federal regulations put the responsibility on the drug company stating, “labeling shall be revised to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.”

In the brief filed in support of its motion, Novartis contends that companies rarely, if ever, change labels under this provision because they know that they ultimately need to obtain FDA approval for the change.

The truthful explanation for its refusal to comply with this provision, would be that Novartis knew that adding a warning would have resulted in a drastic reduction in the profits that the company was enjoying from the “off-label” sale of Elidel to children.

When attempting to use the preemption defense, as a starting point, Novartis, and every other drug company, should be required to explain why it would have been difficult to add a specific warning to the label.

In an amicus brief submitted by the FDA that sides with Novartis overall, the agency quotes regulations and describes the simple procedure used to add a warning, and it takes a whole 30 days. According to the FDA:

“If the manufacturer of a non-generic prescription drug wishes to add or strengthen a warning, the manufacturer may provide FDA with a supplemental submission regarding the proposed labeling change, providing a full explanation of the basis for the proposed change.

“If FDA has not rejected the supplement within 30 days after its submission, the manufacturer may distribute the drug with the new proposed labeling.”

The FDA’s brief also states: “If a drug manufacturer has “reasonable evidence of a causal association” between the use of a drug and a “clinically significant hazard,” the manufacturer has an obligation to seek FDA approval for a labeling change, in order to add a warning of the new potential hazard.”

As far as “reasonable evidence” goes, it would not take a rocket scientist to figure out that if 3 species of animals were developing cancer from Elidel, infants and toddlers weighing between 6 and 30 pounds would probably do so as well.

In its brief, Novartis relies on the FDA’s argument in the preamble that it interprets the FDCA “to establish both a ‘floor’ and a ‘ceiling,’” and thereby preempts state laws imposing greater safety requirements.

However, in the FDA’s own words, liability will only attach, “if the additional statement is unsubstantiated or otherwise false or misleading,” which is certainly not the case with Elidel.

In their brief, the Perrys argue that the FDA does not impose a “ceiling” on truthful, substantiated risk information, which is precisely the type of warning they sought.

In this case, the FDA has never rejected stronger warnings for Elidel and the court held that preemption would only apply if a specific warning about pediatric cancer had been considered and rejected.

In addressing the claims in the FDA’s brief, the opinion states: “To be sure, because of its expertise in the area, the FDA’s construction of its own regulations is likely to carry great weight.”

“But where an interpretation has changed frequently in significant respects,” it points out, “the persuasive force of the argument diminishes.”

The court went on to explain that even if the preamble did represent a change of policy with the force of law, it would not apply to this case. “The FDA,” it said, “cannot retroactively absolve Novartis of a duty it may have owed the Perrys in 2003.”

The opinion also states that “a finding of preemption here will foreclose a remedy that was traditionally available and for which federal law provides no substitute.”

In conclusion, citing a September 23, 2006, New York Times report by Gardiner Harris, the court said, “given the recent concerns about the effectiveness of the FDA’s safety monitoring of recently approved drugs, . . . the availability of state law tort suits provides an important backstop to the federal regulatory scheme.”

Filed under: 2006, cancer, Elidel, Novartis, Preemption

Add Triaminic Vapor Patch to List of Dangerous Patches

Evelyn Pringle June 25, 2006

On June 19, 2006, Novartis Consumer Health issued a recall for the cough-suppressing Triaminic Vapor Patches in the US, about three weeks after Health Canada issued a warning after a Canadian child who chewed on a patch suffered a seizure.

There have been eight adverse events with the patch, all involving ingestion, Navartis spokesperson, Julie Masow, told the Philadelphia Inquirer on June 21, 2006.

The patches were sold over the counter at pharmacies and retail stores and Novartis said it has sold more than 50 million vapor patches since they came on the market in 2000.

The Swiss drug maker warned consumers to stop using the patch immediately and said they should either be discarded or returned to the place of purchase for a full refund.

The patches contain camphor, eucalyptus oil and menthol and are meant to be applied to the chest or throat of children as young as 2 years-old. Novartis said the placement of the patch can allow children to remove them and place them in their mouths. It is difficult to believe that the idea never occurred to the drug maker that a 2 year-old would attempt to pick the cherry-scented patch off and eat it.

Ingesting camphor or eucalyptus oils can cause a burning sensation in the mouth, nausea, headache, vomiting and seizure. Other complaints received by the company associated with the patch include reports of blistering, bruising, scarring, hyperactivity and depigmentation.

Whether the patch will remain off the market is not known. According to a June 21, 2006, Press Release by the LecTec Corporation, in January 2004, LecTec entered into a Supply and License Agreement with Novartis under which LecTec licensed certain of its patents to Novartis for the production of vapor patches.

In response to a question from LecTec, a representative of Novartis indicated that no decision had been made whether to reintroduce the product in certain markets, although the patches would definitely not be reintroduced for use by young children, the press release said.

The royalties received by LecTec under this agreement represented substantially all of the firm’s revenues in fiscal 2005, as well as the first quarter of fiscal 2006. The specific patch that caused the seizure was not manufactured by LecTec, according to Novaris quoted in the press release.

Over roughly the past 25 years, patch medications have become a booming business for Big Pharma. More than 30 different types of patches have been used by 12 million people worldwide for conditions ranging from birth control to heart disease to chronic pain to bladder control. The first antidepressant patch was approved by the FDA this month.

In 2004, patch sales totaled about $3.4 billion, according to the medical market research firm Greystone Associates.

All medication releasing patches work the same, according to Bozena Michniak, who studies transdermal patch delivery systems at the Center for Biomaterials at Rutgers University. The medication seeps through the skin into the bloodstream, and the increased blood flow causes the body to absorb the drug.

As more versions of the medication patches are introduced on the market, medical experts say that many of them are unsafe. Multiple studies have shown that heat has a dangerous effect on the patches, whether from a high fever, exercise or a hot tub. Heat increases the absorption rate of the medication and sometimes with fatal results.

As far back as 1986, a study found that just 20 minutes of bicycling with a nitroglycerin patch increased concentration of the drug two to threefold. Similar results were found after 30 minutes in a sauna, according to an article in Philly.com on March 5, 2006.

But yet there was no public warnings added to the Fentanyl pain patch until 36-year-old Kurt Hophan died in Pennsylvania on March 4, 1994.

Fentanyl, a schedule II narcotic analgesic, is roughly 50-80 times more potent than morphine and is used to manage both pain during surgery and for persons with chronic moderate to severe pain who already are physically tolerant to opiates, according to the US Center for Substance Abuse Treatment.

Mr Hophan applied the patch for pain relief associated with a back injury and went to his bedroom in his mother’s home and fell asleep with a heating pad and an electric blanket.

When the heat from the pad and the blanket came into contact with the patch, the amount of Fentanyl released into Mr Hophan’s bloodstream was estimated to be about 100 times greater than the amount prescribed, according to a judge’s opinion in a lawsuit filed by Mr Hophan’s mother, Elaine Hophan, against the drug’s maker.

In 2001, a jury awarded Ms Hophan $5 million in damages but after an appeal, the case was settled under a confidential settlement agreement.

Fentanyl patches are sold under a variety of brand and generic names. Johnson and Johnson’s Duragesic was the first on the market arriving in the early 1990s. It’s the most popular patch with four million prescriptions filled at US pharmacies last year.

Worldwide sales of Duragesic in 2005 were $1.59 billion, according to J& J’s earnings reports. The cost of a 30-day supply ranges from $348 at Target to $408 at Wal-Mart, according to FDA documents.

On April 5, 2004, J&J issued a recall for defective patches that applied to specific lots of patches, which had a faulty seal that permitted Fentanyl to seep from the patch, resulting in patients being given an overdose of Fentanyl.

On July 15, 2005, the FDA issued a public health advisory about the proper way to use the Fentanyl patches to avoid overdose, in response to reports of deaths in patients using the narcotic patch for pain management.

The Los Angeles County Coroners Office reports a growing number of accidental over-doses by patients misusing the patch: 127 deaths over the last six years, according to a CBS News report on December 20, 2005.

“They’re not getting the relief that they want. Therefore they’re slapping more patches on trying to get that instantaneous relief,” says toxicologist Daniel Anderson. “What they don’t realize is that most of these patches are to be applied over a three-day period.”

Utah statistics according to the latest mortality data from the state Health Department show Fentanyl was related to 29 accidental deaths in 2005, up from nine in 2004, and 13 in 2002, according to the March 14, 2006 Salt Lake Tribune.

Lawsuit are being filed as a result of the high accidental overdose rate. Robert Debry & Associates, in Salt Lake City has taken about a dozen cases involving deaths allegedly from Fentanyl. One lawsuit is filed on behalf of the family of Marilyn Titus who died December 14, 2003, at age 72 and alleges Ms Titus, was suffering from severe back pain, and was sold defective and leaking patches.

In December 2005, surviving family members of two more Utah women filed wrongful death lawsuits, alleging the patches leaked and caused the deaths of both women.

Autopsy reports said the women died from drug poisoning after using pain patches. Both lawsuits claim the women were prescribed the patch and were found dead in their homes within one or two days of using the patch.

Both lawsuits claim negligence for failing to research and design the patch and allege the companies misrepresented the safety of the patch for human use.

Overall, US emergency room doctors saw overdoses of Fentanyl grow from 28 in 1994 to 1,506 in 2002, according to the most recent statistics available from the US Substance Abuse and Mental Health Administration.

In March 2006, the FDA announced it would conduct a review of all medication patches beginning with Fentanyl and the Ortho Evra birth control patch, also made by J& J.

The following month, an April 10, 2006, Long Island Newsday report said that “hundreds” of women had filed lawsuits against Ortho-McNeil, the J&J division that manufactures the Ortho Evra patch.

And there will no doubt be many more filed against the company because in 2005, doctors wrote more than 9.4 million prescriptions for the birth control patch, according to IMS Health, an pharmaceutical industry monitoring firm.

On November 10, 2005, Ortho McNeil, in conjunction with the FDA, issued a warning about the increased risks of blood clots associated with Ortho Evra Patch.

In the new warning, Ortho McNeil admits for the first time that women who use the patch are exposed to up to 60% more estrogen than they would be exposed to if they were taking a birth control pill with 35 micrograms of estrogen. It is widely understood that any increase in the exposure to estrogen also increases the risk of blood clots.

A lawsuit filed in Federal Court in New Jersey on September 2, 2005, by a Georgia woman, who suffered a pulmonary embolism, alleges the company promoted the patch despite knowledge of its health risks, for financial gain while failing to warn of the risks of blood clots and other injuries.

Around the time the company introduced the patch to the market, the lawsuit claims, Ortho’s patent for its contraceptive pill, Ortho Tri-Cyclen, was about to expire, creating pressure to make up for lost revenue.

In November 2005, CBS News aired a story about documents that surfaced in a lawsuit involving a young mother who was paralyzed by a stroke and remained a total invalid, that showed the company had received nearly 500 reports of adverse events between April 2002 and December 2004. During the same time frame, only 61 adverse event reports were filed in connection with all type of birth control pills.

The news segment also revealed that during the same time frame, 4 times as many strokes occurred in women using the patch when compared to women using the pill, even though 3 times more women were taking the pill. Overall, in medically confirmed cases, the risk of blood clots was found to be 14 times more likely to occur in women using with the patch.

Since the FDA only receives reports for between 1% and 10% of the serious adverse drug events, the actual death and injury rate for women on the patch is estimated to be much higher that the number of reports registered so far with the FDA

The Ortho Evra Patch was approved by the FDA in November 2001. Over 4 million women have reportedly used the patch since its approval and it remain on the market today.

Filed under: 2006, allergy drugs, birth control patch, fentanyl, Johnson and Johnson, Novartis, Ortho, patch, settlement, Triaminic Vapor Patch

Reviewing ADHD Drugs – FDA Goes Through the Motions

Evelyn Pringle March 12, 2006

Some of the top-selling drugs of all time are those prescribed to treat attention deficit disorders. Drug companies have physicians in every field of medicine pushing these medications and dole out millions of dollars worth of free samples each year to make sure they are passed out like candy.

A new ADHD drug is set to come on the market that supposedly can keep people awake for days at a time with no problems. Just what we needed, especially for hyper little kids.

I wonder if this means they will remain calm as they sit wide-awake watching TV and playing video games for days while the rest of the family sleeps.

The drug Sparlon is manufactured by Cephalon and is a clone of Provigil, another drug already on the market. Sparlon contains modafinil, the same exact active ingredient contained in Provigil which is approved for the treatment of patients with narcolepsy, sleep apnea and shift work sleep disorder, according to the FDA.

The drug’s approval will be considered by the FDA’s Psychopharmacologic Drugs Advisory Committee at a public hearing scheduled for March 23, 2006.

The day before the Sparlon hearing, the FDA’s Pediatric Advisory Committee is scheduled to meet to discuss neuropsychiatric adverse events and cardiovascular adverse events reported on patients who were treated with ADHD stimulant drugs already on the market.

The drugs under review include Ritalin from Novartis, Adderall and Adderall XR from Shire Pharmaceuticals, Concerta from Johnson & Johnson, and generic versions of Ritalin.

On February 9 and 10, 2006, the FDA’s Drug Safety & Risk Management Advisory Committee held hearings on the same topic, and after reviewing the information provided at the hearing, the panel recommended that black box labels be added to the labels of all stimulants.

However, the FDA is not bound by the recommendations of its advisory panels, and critics of the drugs say the close 8-7 vote by the panel, means there will be spirited debate within the agency over whether black box labels will be added.

Several members of the panel said they voted for the warning in part, because they were alarmed over the sharp rise in prescriptions written for both children and adults. During the hearing, the committee was informed that between 1999 and 2003, roughly 78 million prescriptions were written for children under the age of 18, and 14 million more were written for adults.

In a stark contrast, only 190 million prescriptions were issued for children and adults during the 12 year period between 1992 and 2004.

According to the FDA numbers on adverse events, between 1999 and 2003, there were 25 deaths reported for persons using ADHD drugs, and 19 were children. The agency also acknowledged that more than 50 cases of cardiovascular-related events were reported in the same time period including stoke, heart attack, hypertension, palpitations and arrhythmia.

Critics say the numbers revealed at the hearings represent a gross understatement because only 1% to 10% of adverse reactions are ever reported to the FDA, and it would therefore be better to add a black box now and remove it later if studies prove there is no link between the stimulants and sudden death and heart disease.

Supporters of the drugs, say the warning is based on inconclusive evidence and would deter physicians from prescribing the medications and scare patients away from taking the drugs.

Because Cephalon claims Sparlon should not be classified as a stimulant, analysts predict the company could get a boost if the FDA agrees and requires the other drugs to carry a black box warning. One of the issues discussed at the March 23, hearing will likely be how to distinguish Sparlon’s labeling from other ADHD drugs.

If approved, Sparlon will be co-marketed under an agreement with Johnson & Johnson, which will focus on the pediatric market through its McNeil Consumer & Specialty Pharmaceuticals unit.

McNeil’s sales team will promote Sparlon to psychiatrists, pediatric neurologists and pediatricians, while Cephalon’s 400-person sales force will focus on non-pediatric specialists and primary care physicians.

When Cephalon requested FDA approval for Sparlon, it submitted the results from three clinical trials on children aged 6 to 17 that the company said indicated better results in children taking Sparlon compared to children who received a placebo. Each trial lasted 9 weeks and the most common side effects noted were loss of appetite, mild insomnia and headaches.

But Cephalon has not been sitting idle while waiting for approval of its Provigil clone. Last year it had to figure out a way to deal with the fact that Provigil’s patent was set to expire in 2006. Through some last minute legal footwork, the company was able to negotiate agreements with 4 generic firms that will allow Cephalon to continue to sell the drug unchallenged until at least 2011

Provigil’s approval for a silly diagnosis like “shift-work sleep disorder” is a good example of disease-mongering, described in the book, “Selling Sickness: How The World’s Biggest Pharmaceutical Companies Are Turning Us All Into Patients,” by Ray Moynihan and Alan Cassels, which explains how drug companies foster the creation of bogus disorders to create markets for their pills, through “medicalization” of normal states of health.

In the same vein, many experts say the sale of ADHD drugs in general is nothing but a racket. Dr Fred Baughman, a board certified child neurologist and Fellow of the American Academy of Neurology, calls ADHD the “greatest health care fraud of modern times.”

Clinical social worker Peter Dwyer, has seven years’ experience working with troubled children, and has served as director of a large therapeutic foster care program. He also attributes the ever-rising sales numbers for ADHD drugs to a grand marketing scheme.

“It is easy to see why stimulants dominate the treatment of ADHD,” he says, “drug companies spend over $20 billion a year on promotion – more than they spend on research.”

“The bottom line,” Mr Dwyer explains, “professionals and the public are bombarded with a stream of “research” and “information” financed and spun by the people who make and sell these drugs.”

“The conflict of interest is palpable,” he adds.

And anyone who believes Provigil is free of the side effects associated with other ADHD medications needs to speak to Susan Florence who experienced a terrifying adverse reaction to the drug.

“I took one pill and I thought I was coming out of my skin,” she recalls, “I felt as if someone had climbed inside me.”

“It was one of the worst experiences of my life,” she says.

Nonetheless, Cephalon has done an excellent job of promoting Provigil. The US Air Force has even adopted the drug as one of its official “go pills” for pilots whose missions stretch out more than 12 hours, according to Business Week on November 1, 2004.

Ever since Provigil hit the market, Cephalon stayed busy figuring out ways to promote its off-label use for a multitude of ailments including ADHD, and with obvious success. SG Cowen & Co analyst, Eric Schmidt, told Business Week he figures more than 50% of Provigil sales are for unapproved uses.

And 50% in off-label sales adds up to enormous profits. In 2004, US doctors wrote 1.9 million prescriptions for Provigil, generating $414 million in sales. In 2005, Cephalon saw Provigil sales reach $512 million, according to Forbes.com on March 13, 2006.

While waiting for Sparlon to be approved, the company has been using every trick in the book to boost sales of Provigil for the treatment of ADHD.

For instance, Dr Fletcher Taylor, from Tacoma, Washington, was paid to meet with small groups of doctors to talk about Provigil.

He conducted a study on the use of Provigil for ADHD, which he claims showed positive results. However, according to Business Week, Dr Taylor says “he does not bring up the use of Provigil for ADHD in his talks, but he answers questions – as he is permitted to do – if one of the doctors in the group brings it up.”

“Usually people do ask,” he told Business Week.

I’m quite sure they do ask, probably much like the people on TV who used to just happen to step out of the audience to be cured by faith-healer 50 years ago.

Cephalon also employs the well-known off-label marking technique of funding continuing medical education seminars (CMEs), under the guise of providing doctors with information related to how certain ailments can be treated by drugs that the company just happens to sell.

For example, Cephalon paid for a CME that focused on the treatment of daytime sleepiness experienced by Parkinson patients and explained how Provigil might be a useful therapy.

The sponsor of the program, a firm called Projects in Knowledge, told Business Week that Cephalon paid for the program but had no input on the material discussed.

And of course I believe that.

Another tried and true method of promoting off-label use involves publishing the results of favorable studies funded by drug companies in medical journals. “Journals have devolved into information laundering operations for the pharmaceutical industry,” according to Richard Horton, editor of the Lancet, in March 2004

In a prime example of this practice, the August 4, 2005 New England Journal of Medicine, published a report on a study funded by Cephalon in which the lead author, Dr Charles Czeisler, from Harvard Medical School and Brigham and Women’s Hospital, had a professorship endowed by $2 million from Cephalon.

In the report, Dr Czeisler claimed night-shift workers remained more alert with Provigil and wrote a glowing summary of the study. “I would characterize [Provigil] as the treatment of choice with patients with shift-work disorder,” he said.

However, Dr Robert Basner, director of Columbia University’s Cardiopulmonary Sleep and Ventilatory Disorders Center, published an editorial on the study in the same issue of the NEJM and said the researchers’ data showed only slight improvements in workers wakefulness and productivity with Provigil, and pointed out that the drug seemed to exacerbate insomnia for some patients.

“That’s not a very robust endorsement of the drug coming from the investigators themselves,” Dr Basner wrote. “This drug is little better than nothing in terms of making them less sleepy during shift work at night,” he added.

Experts pretty much agree that Sparlon will be approved for treating children with ADHD so before too long the “little better than nothing” clone will not doubt be ringing up the cash registers all over the US.

Filed under: 'ADHD', 2006, Adderall, Cephalon, Concerta, FDA, FDA hearing, Johnson and Johnson, Novartis, Provigil, Ritalin, Shire, Sparlon

FDA Runs Protection Racket For Big Pharma

January 7, 2007 Evelyn Pringle

Why would Americans trust the FDA to regulate the pharmaceutical industry? Since the Bush administration took office the FDA has become the industry’s partner in crime.

The most notorious protection scheme put in place by the FDA and Big Pharma is the preemption policy that bans private lawsuits against drug companies in state courts once a drug and its label have been approved by the FDA.

On January 18, 2006, the FDA issued new rules for the labeling of prescription drugs, and in the preamble to the rules on page 43, the FDA says, State law actions “threaten FDA’s statutorily prescribed role as the expert Federal agency responsible for evaluating and regulating drugs,” requiring lay persons to second-guess its expert assessments of a drug’s risks and benefits.

So, after all of the concerns raised about the FDA’s failure to protect consumers against dangerous products over the last several year, by top experts from all over the world, the FDA has hereby declared itself the sole authority on decisions regarding prescription drugs, including whether a drug’s label contains adequate descriptions of indications for use, risks and benefits.

In an October 6, 2006, articled titled, “The Doctrine of Preemption,” Stan Kaufman aptly refers to the new policy as the “Doctrine of Preemptive Crony Capitalism.” When announcing this multi-billion dollar immunization gift to Big Pharma, the FDA told drug makers:

“We think that if your company complies with the FDA processes, if you bring forward the benefits and risks of your drug, and let your information be judged through a process with highly trained scientists, you should not be second-guessed by state courts that don’t have the same scientific knowledge.”

A statement saying the complete opposite was made in 1996, by the FDA’s Chief Counsel in a speech that said the FDA had a “longstanding presumption against preemption” and that “FDA’s view is that FDA product approval and state tort liability usually operate independently, each providing a significant, yet distinct, layer of consumer protection.”[

The preemption claim reverses a long-standing policy of permitting State actions intended to protect consumers and undermines the States’ ability to protect their citizens, yet State and local entities were given no opportunity to object to it.

Under Executive Order 13132, issued first by President Reagan, and then reissued by President Clinton, the FDA is supposed to consult with State and local authorities about the effects of each regulation it issues that affects the States.

Nowhere in the proposed rule did the FDA provide notice or seek comment on the preemption provisions added to the preamble. In the only proposed rule known to State and local officials, the FDA said that the regulation would not preempt State law. In fact, the language published in the Federal Register on December 22, 2000, explicitly stated that “this proposed rule does not preempt state law.”

The rule requested comment on products liability issues, but only by asking whether the new “Highlights” section raised liability concerns and, if so, how the FDA might alleviate those concerns without eliminating the Highlights section. This request can hardly be called “notice” of the preemption statement that suddenly appeared in the preamble in 2006.

By relying on this false representation, State and local authorities were robbed of any opportunity to object to the preamble. In a January 2006, letter to Michael Leavitt, Secretary of Health and Human Services, the National Conference of State Legislators called the regulation a “thinly veiled attempt on the part of FDA to confer upon itself authority it does not have by statute.”

The NCSL also stated the failure to allow for an appropriate comment period constitutes “an abuse of agency process and complete disregard for dual system of government.”

Ken Suggs, president of the Association of Trial Lawyers of America, was quoted in the January 19, 2006 Washington Post, as saying, the “fact that the drug industry can get the FDA to rewrite the rules so that CEOs can escape accountability for putting dangerous and deadly drugs on the market is the scariest example yet of how much control these big corporations have over the political process.”

Legal experts point out that it was never the intent of Congress to preempt private lawsuits in State courts, and that in fact, when Congress was considering the Food, Drug, and Cosmetic Act of 1938, it specifically rejected a proposal to include a private right of action for damages on the ground that such a right already existed under State common law.

According to Houston attorney, Robert Kwok, who handles complex pharmaceutical litigation involving drugs such Fosamax, Norvasc and SSRI antidepressants like Celexa:

“The real losers from this attempted power grab would be the millions of Americans who depend on safe drugs. Without the protection of state laws Big Pharma can ride shipshod over Americans who are injured by their unsafe drugs. That’s unacceptable and I’m seeing even conservative judges resist it.”

Many members of Congress have also weighed in on the issue and reaffirmed that Congress never intended to preempt State claims in a February 23, 2006, letter to Michael Leavitt, Secretary of Health and Human Services, from Representatives Henry Waxman (D-Calif.), John Dingell (D-Mi.), and Sherrod Brown (D-Ohio).

Rep. Maurice Hinchey (R-NY) and Senator Edward Kennedy (D-MA), have threatened to fight preemption through legislation if necessary. Rep. Hinchey issued a press release on January 18, 2006, immediately after the policy was announced, stating that the “FDA has once again gone to bat for the drug industry by fully endorsing a policy that shelters pharmaceutical companies from Americans who want to file lawsuits because a drug has made them or a loved one seriously ill, or in some cases caused death.”

Rep. Hinchey also called it “the latest example of the FDA sticking its nose where it does not belong and treating the drug companies as clients rather than regulated entities.”

The FDA’s language on page 38 of the preamble that states “whether it be in the old or new format, the Food, Drug and Cosmetic Act preempts conflicting or contrary state law,” appears to imply that the preemption policy is retroactive.

Part of the language also says that lawsuits against doctors are preempted for failure-to-warn patients of risks associated with a drug, apparently even when a drug is prescribed “off-label,” for a use other than those approved by the FDA.

“Pre-emption would include not only claims against manufacturers,” the FDA states, “but also against health-care practitioners for claims related to dissemination of risk information to patients beyond what is included in the labeling.”

The FDA has never before, in its entire history, claimed that a drug label preempts actions against health care professionals for failure-to-warn patients about risks. In fact, labels carry no information about the risks or benefits of “off-label” uses.

Critics see this language as an attempt to immunize all the doctors who the industry has convinced to over-prescribe drugs to treat conditions or patient populations for which the drugs have never been approved as safe and effective to increase profits.

“Doctors need to be held just as accountable as the drug manufacturers when things go wrong,” attorney Kwok says.

“The profession of medicine is in danger of being totally co-oped by the business of medicine,” he warns, “with more and more of the burden is being placed on the consumer.”

“And with only minimum consumer protection standards set by the FDA, that isn’t very reassuring,” Mr Kwok notes.

“I predict there could be a flood of litigation,” he says, “before FDA policy changes any more.”

In any event, restrictions that the FDA places on drug labeling do not prohibit drug companies from disseminating warnings about a danger by other means. When it originally promulgated these regulations, the FDA made clear that:

These labeling requirements do not prohibit a manufacturer, packer, re-labeler, or
distributor from warning health care professionals whenever possibly harmful adverse effects associated with the use of the drug are discovered. The addition to labeling and advertising of additional warnings, as well as contraindications, adverse reactions, and precautions regarding the drug, or the issuance of letters directed to health care professionals (e.g., “Dear Doctor” letters containing such information) is not prohibited by these regulations. 44 Fed. Reg. 37434, 37447 (June 26, 1979).

One of the main authors of the new labeling rules was the FDA’s Chief Counsel at the time, Daniel Troy, who in previous employment fought the FDA in court to allow drug companies to promote drugs to doctors for “off label” use.

Its now obvious when looking back, that Mr. Troy was appointed by the Bush administration to implement tort reform under the guise of preemption, and under the cover of the Office of Chief Counsel at the FDA.

In the midst of the Vioxx and SSRI antidepressant disasters, instead of going after the drug makers for knowingly injuring hundreds of thousands of consumers with dangerous products, Mr. Troy devoted the majority of his time on the clock to filing five amicus briefs on behalf of Big Pharma to be used against the very citizens who were paying his salary.

In his briefs, Mr. Troy focused his main attention on protecting the profits of the makers of SSRIs, drugs second only to Vioxx when it comes to the concealment of studies and information about harm that if revealed, could have prevented tens of thousands of deaths and injuries over the past 20 years.

And even though there has been an infinite number of reports over the past decade regarding an increased risk of suicide with SSRIs, instead of withdrawing the approval of the drugs, requiring more studies, or demanding a warning be added to their label, Mr. Troy did nothing to protect potential SSRI victims as Chief Counsel of the FDA.

In late 2004, Mr. Troy quit the FDA to go back into private practice to once again represent pharmaceutical companies openly against private citizens, only with the added benefit of using the preemption defense he put in place.

On October 9, 2006, Mr. Troy published an article in the Legal Times, that said, “I was also at the FDA while January’s Physician Labeling Rule, which contains a statement in its preamble about the FDA’s pre-emption authority, was written.”

“And I now,” he states in an obvious ad for new clients, “advise and represent companies confronting state-law claims that implicate the pre-emptive effect of FDA requirements.”

In the Times article, Mr. Troy points out the importance of drug companies staying cozy with the FDA to ensure success in future litigation. “Savvy companies,” he wrote, “are recognizing that how they interact with the FDA today may profoundly affect their pre-emption defenses in the future.”

“They are trying to ensure their communications with the agency are as formal as they can be,” he said, “in light of commercial considerations and the need to stay on the FDA’s good side.”

“More formal communications,” he advises, “can help buttress a future case for why a particular state law claim should be pre-empted.”

In the article, Mr. Troy brags that his filing of FDA briefs on behalf of Big Pharma “has reduced the negative consequences of the current pharmaceutical-liability regime.”

But for once, he at least mentions that it cost the tax payers plenty. “FDA involvement in state-law cases is not an ideal solution,” he writes, “not least because each instance of such involvement involves the costly investment of substantial agency resources.”

It should be noted that two years before Mr. Troy filed his first brief as a kick-off for the preemption policy, the “costly investment of substantial agency resources” went for an FDA brief, in which the FDA acknowledged “the historic primacy of state regulation of matters of health and safety” and the appropriateness of a presumption against preemption where the state-law claims allege defective design, negligent manufacturing, or failure-to-warn in, Buckman v. Plaintiffs’ Legal Committee, 531 US 341 (2001).

In the Legal Times, Mr. Troy goes on to explain that the new labeling rule is intended to limit the direct involvement of the FDA in lawsuits. “The preamble to that rule,” he says, “makes an official statement of FDA’s views on preemption easily available to courts hearing state-law tort cases.”

“If courts give appropriate deference to this statement of FDA’s considered judgment,” he notes, “FDA will not be forced to file briefs in individual cases.”

Until reading this article, its likely that most people had never realized that Mr. Troy was “forced” to file briefs on behalf of Big Pharma while he worked at the FDA.

In a March 31, 2006 paper, titled, State-Level Protection for Good-Faith Pharmaceutical Manufacturers, Mr. Troy can be found advising State lawmakers to pass shield laws for Big Pharma based on a Michigan model, to “help to reduce the negative consequences of the current pharmaceutical-liability regime,” he says.

“In so doing,” he states, “they would help to encourage the development of new drugs, preserve the availability of existing drugs, reduce upward pressure on drug prices, and assure rational prescribing.”

Such a statement might be a wee bit credible if it also included a suggestion for the lowering of the multi-million dollar annual salary and benefit packages enjoyed by Big Pharma CEOs or a reduction in the billions of dollars that are spent each year on illegal off-label promotion and marketing schemes.

For all the whining he does about litigation keeping products off the market, Mr. Troy cannot cite a single case in which a failure-to-warn claim interfered with the FDA’s federal regulatory authority or kept a drug off the market. In fact, in a lecture to Big Pharma attorneys in December 2003, on how to use the preemption defense, Mr. Troy told the attorneys that the FDA had “no good evidence” showing product liability concerns “keep good products off the market,” even though he had “combed the literature” to find such evidence.

Apparently to help resolve this nagging little problem, Mr. Troy told the defense attorneys to pay for research to find some evidence to back this claim even if it was weak, stating: “you guys really shoot yourself in the foot by not funding research to this effect. … I’ll even take anecdotal evidence and stories if you have them.”

Mr. Troy filed the FDA’s first brief in support of Big Pharma in September 2002, in the California Zoloft case titled Motus v. Pfizer, after he was contacted by Pfizer attorney, Malcolm Wheeler, in the summer of 2002, requesting that he get the government involved to help Pfizer win the preemption argument.

Despite the fact that Pfizer had paid Mr. Troy’s law firm over $358,000 in the year before he became Chief Counsel, Mr. Troy argued later that he did not become involved in the case until after the 1-year grace period in which employees may not participate in activities involving former clients. From all public accounts, the time period elapsed less then a month before he entered the case.

In the brief, Mr. Troy argued that any warning that suggested a link between Zoloft and suicidality would have been false and misleading, and the FDA would have rejected any effort to add such a warning. However, that argument contradicts 21 CFR § 314.126(b), which requires warnings to be added based on reasonable evidence of an association, even absent proof of a causal relationship. The preemption issue was never decided in Motus because the case was concluded on unrelated grounds.

Legal experts say the preemption defense will not only be used in SSRI-related suicide cases, it will be applied in SSRI cases involving the failure-to-warn about other types of injuries and deaths caused by these drugs as well.

For instance, Big Pharma will no doubt attempt to preempt cases filed on behalf of infants born with birth defects to mothers who unwittingly took the drugs during pregnancy, such as with Lacee Shore, who was prescribed Celexa during her first trimester of pregnancy and as a result, her baby, Gavin Shore, was born with serious heart birth defects and diagnosed with Shone’s Complex, which can lead to the obstruction of blood flowing to the body from the left side of the heart.

Gavin has already gone through several surgeries in attempt to correct the heart defects and will have to undergo more in the future.

The successful use of the preemption argument in a case such as this, where the drug maker, Forest Laboratories, could and should have warned doctors and pregnant women about the possibility of birth defects associated with Celexa, would leave the Shore family strapped with the burden of life-long medical costs related to Gavin’s condition.

According to attorney Kwok, who is handling the Shore case, the birth defect situation is even more devastating than with patients harmed by Vioxx because the Celexa victims are so young. “Their whole lives,” he says, “if they survive, will be under the threat of illness and additional surgery, with a very poor prognosis.”

Mr. Kwok points to a 1990 study conducted at the University of Michigan that shows the outlook for infants born with heart defects like Gavin is very poor. “One quarter of patients die after their second operation,” he says.

“The second operations are very often necessary,” he explains, “because of the complexity of the heart problem.”

Forest Labs knew about the potential for birth defects caused by Celexa because more than two years before Gavin was born, on June 9, 2004, Web MD reported that the FDA was concerned about reports that SSRIs may cause adverse effects to babies born to mothers taking the drugs late in pregnancy.

According to Web MD, the FDA had been receiving reports for 10 years. In fact, it said that hundreds of reports on adverse effects in babies were received involving all the SSRIs sold in the US, which would include Prozac, Paxil, Luvox, Zoloft, and Celexa.

In July 2004, the FDA finally asked the SSRI makers to change the labels, warning that some infants had developed problems requiring tube feeding, respiratory support, and prolonged hospitalizations.

On September 1, 2005, the BBC reported that Danish and U.S. scientists found that cardiac birth defects appeared to be 60% more likely in newborns when women used SSRIs.

Studies show that women are prescribed SSRIs twice as often as men and yet the drug makers have made no effort to evaluate the use of these drugs with pregnant women. And as a result, Mr. Kwok says, “new moms are finding out too late that the Celexa they took was putting their unborn baby in grave danger.”

A successful preemption ruling would go a long way as far as protecting profits against damage awards based birth defects, because pregnant women represent a major share of the market. According to a May 2005, study in the Journal of American Medical Association, 80,000 pregnant women are prescribed SSRIs in any given year in the U.S., which means there are bound to be many cases where babies were born with birth defects.

The majority of courts that have addressed the preemption argument have ruled against it. One of the first federal courts to specifically rule against the FDA’s preamble position was a Nebraska District Court on May 31, 2006, in Jackson v. Pfizer, where the plaintiffs’ son took both Zoloft and Effexor and then committed suicide.

The parents alleged that the drugs caused their son to commit suicide and Nebraska law required additional warnings about the suicide risk. The drug maker defendants moved for summary judgment claiming that the State law claims were preempted by the FDA.

The court said that the claims were not preempted because the federal regulations did not conflict with State law and specifically held that there was no Congressional directive that the field was preempted.

The court stated the FDA preamble was not persuasive and pointed out that the Eighth Circuit had adopted the proposition that the FDA prescribes only minimum standards and the Fourth Circuit had declared that complying with federal regulations does not release a manufacturer from liability.

The court also noted that the FDA “failed . . . to allow the states an opportunity to participate in the proceedings prior to a preemption decision,” and dismissed the FDA’s brief stating that it “will not treat amicus briefs as the force of law.”

On May 25, 2006, a federal court in Pennsylvania was the first to grant the FDA’s preemption rule full deference in a wrongful death and survival action, with failure-to-warn claims against Paxil maker GlaxoSmithKline, and generic Paxil maker Apotex, in Colacicco v. Apotex, Inc, Civ No 05-cv-5500, 2006 WL 1443357 (E.D. Pa. May 26, 2006).

In this case, the plaintiff alleged that his wife’s suicide resulted from the drug makers’ failure-to-warn of the increased risk of suicide linked to Paxil and its generic equivalent.

The judge on his own initiative, invited the FDA to file a brief. The current Chief Counsel, Sheldon Bradshaw, went to bat for the drug makers and filed a brief at record speed within 20 days, urging the court to dismiss the lawsuit on the basis of preemption, stating that in October 2003, when Paxil was prescribed to the suicide victim, “there was no reasonable evidence available at the time of an association between adult use of the drug and suicide.”

The FDA argued that any such warning regarding an association between Paxil and suicide would have been false or misleading, and thus would have constituted misbranding under the FDCA.

The plaintiff responded by arguing that the court should not afford deference to the brief because 21 C.F.R. § 314.70, does permit manufacturers to strengthen labels without FDA approval and the FDA has no authority to simply declare that a drug is misbranded.

The court disagreed and determined that it was to give significant deference to the amicus brief based on the U.S. Supreme Court’s decisions in Chevron, Medtronic, and Geier which state that an amicus brief is an appropriate form to express preemptive intent and held that the principles of deference do not permit a court to question the FDA’s interpretation of its own regulations.

The plaintiff argued that the preamble which was promulgated in 2006 could not be retroactively applied to the October 2003, death of his wife. However, the Court said that preemption could be applied retroactively because the preamble simply clarified the FDA’s “longstanding views on preemption,” and characterized the preamble as an “interpretive rule,” rendering retroactivity concerns “irrelevant.”

The Court went on to say that even if the preamble did not apply retroactively, it would have found preemption anyway based on the views previously expressed in amicus briefs by the FDA.

An appeal is pending on the Colacicco decision, and the case has drawn amicus support from a dozen scientists and doctors who contend that preemption “would threaten the public health and eliminate an important counterpart to the public health objectives of the FDA.”

The national non-profit consumer advocacy organization, Public Citizen, the Trial Lawyers for Public Justice, a national public interest law firm, and the Association of Trial Lawyers of America, an international coalition of attorneys, law professors, paralegals, and law students, have together filed an amicus brief supporting Mr Colacicco, stating:

“Products liability lawsuits help to protect patients from drugs with undisclosed risks because the potential for being held liable for harm caused by their products provides a powerful incentive for drug companies to make their products as safe and effective as possible and to revise labels as soon as new risks become apparent.

“Furthermore, because FDA lacks authority to subpoena documents from the companies it regulates, products liability lawsuits help to uncover information that can lead to safer products.”

In fact, the group points out, since at least several months before the victim’s suicide, the FDA had been reviewing data about a possible link between SSRIs and suicidality, and the agency issued a Public Health Advisory on the topic in October 2003, the same month that Mrs. Colacicco died.

The amicus brief also notes that the FDA’s preemption statement lacks the “consistency” needed to warrant any degree of deference because prior to 2002, the FDA’s consistent view was that State common law was not preempted by federal drug regulation. “For example,” the brief wrote, “in both 1979 and 1998, in preambles accompanying various drug regulations, FDA stated that state tort law did not interfere with federal regulation.”

In 1998, when addressing pharmacists’ provision of written patient information for “Medication Guides,” when issuing the final rule, the FDA rejected calls for the agency to express an intent to preempt State regulation of labeling requirements stating:

“FDA regulations establish minimal standards necessary, but were not intended to preclude states from imposing additional labeling requirements. States may authorize additional labeling but they cannot reduce, alter, or eliminate FDA-required labeling.” 63 Fed. Reg. at 66384.

According to the amicus brief, “The authority to regulate drug labeling may carry with it the authority to address state drug labeling regulations, but it does not carry with it authority to determine the preemptive effect of federal regulation on state common-law compensation systems.”

It appears that the FDA’s own regulations acknowledge that preambles are not statements of law and that they should not be presented as such in legal proceedings.

The amicus group states that the preamble is not part of the regulation, will not appear in the Code of Federal Regulations, and does not have the force of law. “In fact,” the brief notes citing FDA regulations, “a longstanding FDA regulation provides that a statement in a regulatory preamble constitutes only an “advisory opinion.”

The FDA recognizes that an advisory opinion may be used to “illustrate acceptable . . . procedures or standard, but not as a legal requirement,” the brief points out.

“Having made no effort to legislate on the topic of drug-related damages remedies,” the brief concludes, “Congress can hardly be said to have authorized FDA to supersede the damages remedies traditionally provided by the states.”

There was an extremely important preemption ruling handed down on June 9, 2006, in the Vioxx case of Doherty v. Merck prior to the beginning of the actual jury trial. Merck moved to dismiss the failure-to-warn claim arguing that the preamble barred claims with respect to FDA approved drugs.

The June 9, ruling from the bench, drew massive attention to the case when New Jersey Superior Court Judge, Carol Higbee, refused to exclude the claims.

“The preamble, as I see it, is a political statement by the FDA,” she said.

“The primary purpose of it,” she stated, “is to criticize state courts and to set forth the FDA’s position, not to criticize state courts so much as to set forth the FDA’s position that they believe there should be federal preemption of all tort actions.”

“What the preamble is saying,” Judge Higbee noted, “is the FDA should be the final word.”

She refused to dismiss the claims based on the preamble she said, because it “has nothing to do with science.” In conclusion, she told Merck defense attorneys:

“It has nothing to do with what happened back in 2000, 2001, 2002, when these issues were being debated. It is contrary to the U.S. Supreme Court’s decisions. It is contrary to all the law on preemption.

“And I am not going to allow you to use it.”

Merck later enjoyed a victory at trial when a jury decided that Vioxx was not the main cause of Elaine Doherty’s heart attack, but a favorable ruling on the preemption issue prior to trial could have potentially saved the company billions of dollars. According to the company’s SEC filings, as of October 9, 2006, Merck is a named defendant in about 13,850 Vioxx cases in the New Jersey State court coordinated litigation.

The next victory using the preemption argument was a major win in August, 2006, when a California court dismissed the Celebrex failure-to-warn claims against Pfizer, In re Bextra and Celebrex Marketing Sales Practices and Product Liability Litigation, No M: 05-1699 CRB, 2006 WL 2374742 (N.D. CA, August 16, 2006).

In opposing the motion, the plaintiffs argued that because the FDCA does not provide a monetary remedy, Congress must not have intended the FDA to have authority over damage claims and that the FDA’s position on preemption was not entitled to deference because it was clearly erroneous and inconsistent with the regulations.

Saying the FDA specifically considered the safety risks about Celebrex alleged in the lawsuit and determined the risks should not be included on the label, the court said the failure-to-warn claims “conflict with the FDA’s determination of the proper warning and pose an obstacle to the full accomplishment of the objectives of the FDCA.”

But the judge refused to dismiss the false advertising claims. The plaintiffs argued that the Celebrex ads were false and misleading because they exceeded the labeled and approved gastrointestinal benefits and also minimized the established risks of the drug.

Pfizer claimed that because it submitted the ads for FDA approval, and the FDA did not object, the FDA had determined that the ads were accurate and struck a fair balance of the risks and the benefits of Celebrex.

However, the court refused to preempt the claims without a record showing that the FDA had reviewed each ad and approved it. The court also pointed out the FDA’s silence about whether its regulations preempt false advertising claims, in contrast to its stated position on failure-to-warn claims.

A little over a month later, on September 29, 2006, across the country in New Jersey, the court in McNellis v. Pfizer, refused to allow the preemption defense based in part on the fact that the text of FDA regulations had remained unchanged for years, and the regulations did not conflict with New Jersey’s failure-to-warn laws.

The McNellis Zoloft-suicide case comes with a history. On December 29, 2005, the U.S. District Court for the District of New Jersey had also denied Pfizer’s original motion for summary judgment. The court reasoned that the FDA’s approval of a label creates only a minimum standard and that the drug maker may strengthen the warnings as long as the new warning is not false or misleading.

After the FDA published the new rule and preamble with the preemptive language in January 2006, Pfizer filed another motion asking the court to vacate the order denying summary judgment, or to certify the question for interlocutory appeal

In opposing the motion, Ms. McNellis said that the preamble amounted to nothing more than the FDA’s opinion on preemption; the same opinion expressed previously by the FDA in amicus briefs, and the same opinion already rejected by the court. It is irrelevant that this opinion now comes in the form of a preamble to a regulation rather than an amicus brief, she said.

In her brief filed on March 2, 2006, Ms. McNellis argued that the FDA had also exceeded its authority, stating:

“In this instance, an executive agency, the FDA, has expressed an opinion that Congress has never agreed to. Without notice or comment, the FDA found it within its jurisdiction to go against the wishes of Congress as well as the wishes of those states which have product liability failure-to-warn statutes.”

Ms. McNellis also pointed out that the last six courts to decide the issue “have found, consistent with this Court’s finding, that the FDA regulations establish minimum requirements such that they do not preempt state tort laws.”

She also noted that the preamble was not in effect at the time that her father committed suicide as a result of taking Zoloft.

The court held that regulations allow a drug company to increase warnings when new risks emerge, that the Food, Drug and Cosmetic Act does not contain a preemption clause, and that Congress gave no implicit empowerment to the FDA to preempt State law.

Following the McNellis decision, on October 16, 2006, a federal court in Pennsylvania refused to grant the drug maker’s preemption motion on the failure-to-warn claims in Perry v. Novartis Pharma Corp, — F Supp 2d —-, 2006 WL 2979388.

This case involved Elidel, a drug used to treat eczema, prescribed to Andreas Perry when he was 2-years-old. Six months after he began using the cream, in October, 2003, Andreas was diagnosed with a form of cancer known as lymphoblastic lymphoma.

Elidel belongs to a class of drugs known as calcineurin inhibitors, so called because they reduce immune activity by inhibiting the activity of the enzyme calcineurin. Prior to the approval of Elidel for treating skin conditions in children over 2 years of age, calcineurin inhibitors were used as systemic immunosuppressants in organ transplant patients.

Systemic use of the drugs has long been known to increase the risk of cancer and the labels on the drugs prescribed to organ transplant patients say so. But because Elidel is applied topically for eczema, it was not known at the time of approval in December 2001, whether long-term use posed a risk of cancer.

This case illustrates why drug companies must be made to alert the public of known dangers as soon as they are known. On February 15, 2005, an FDA advisory committee met to discuss calcineurin inhibitors. In particular, reports of “off label” use of the drugs in children under two caused concern for some members of the committee.

At the meeting, the committee voted to add a “Black Box” warning about the possible increased risk of cancer associated with the topical use of Elidel, and the lack of long-term safety data on the use of the drug.

On March 10, 2005, the FDA told the drug maker to add a “Black Box” warning and issued a public health advisory about the possible cancer risk. However, it was nearly a year later when Novartis finally got around to adding a “Black Box” warning to Elidel’s label on January 19, 2006.

In their brief in opposition to the preemption motion to dismiss, the plaintiffs said that the FDA’s broad claim of preemption is not entitled to deference, “whether it is expressed in the January 2006 Preamble to the Final Rule,” or “in amicus curiae briefs filed by the agency in support of drug manufacturers.”

“The FDA’s claims,” the brief wrote, “which are tantamount to an advisory opinion, lack the force of law and contradict the FDA’s governing statute, its regulations, and its regulatory purpose.”

It also noted that the FDA’s current opinion directly opposes the FDA’s longstanding views on preemption. “For these reasons,” the brief pointed out, “a majority of courts that have considered this issue, both before and after the FDA issued the Preamble, have held that FDA approval of labeling does not preempt state failure-to-warn claims.”

In denying Novartis’ preemption motion, U.S. District Court Judge, Stewart Dalzell, of the Eastern District of Pennsylvania, wrote in the decision that the FDA’s new “Preamble is not entitled to any special consideration in our analysis.”

Where the agency attempts to “supply, on Congress’s behalf, the clear legislative statement of intent required to overcome the presumption against preemption,” no deference is warranted, he noted.

In reaching its decision, the court said preemption would only apply if a specific warning about Elidel and pediatric cancer had been considered by the FDA and found to be unnecessary and that had not happened in this case.

In discussing the FDA’s assertions in its amicus brief, the court stated, “To be sure, because of its expertise in the area, the FDA’s construction of its own regulations is likely to carry great weight.”

“But where an interpretation has changed frequently in significant respects,” it wrote, “the persuasive force of the argument diminishes.”

The court also said that even if the Preamble represents a change of policy with the force of law, it would not apply to this case. “The FDA cannot retroactively absolve Novartis of a duty it may have owed the Perrys in 2003,” it wrote.

The court also noted that the FDCA provides no remedy for an injured consumer and said, “a finding of preemption here will foreclose a remedy that was traditionally available and for which federal law provides no substitute.”

In its decision, the court made an interesting observation about the viability of the preemption defense on failure-to-warn claims based on other available methods of warning the public about the dangers of a drug, stating:

“It is worth noting that, even where FDA regulations or other federal law prevent a manufacturer from modifying the approved labeling, a modification of the label is not the only form that a warning could take.

“If, for example, a plaintiff claimed that a manufacturer was negligent in not sending a letter to prescribing physicians or other health care professionals, that might present a different case, even if modification of the approved labeling were prohibited.”

In conclusion, citing a September 23, 2006, New York Times report by Gardiner Harris, the court said, “given the recent concerns about the effectiveness of the FDA’s safety monitoring of recently approved drugs, . . . the availability of state law tort suits provides an important backstop to the federal regulatory scheme,” and further stated:

“If, at some future date, Congress determines that FDA monitoring is sufficiently effective on its own to warrant the elimination of state law incentives for manufacturers to provide adequate warnings, it also has the authority to declare that failure-to-warn suits, like the Perrys’ action, are preempted.”

“Until it does so, however,” the court said, “in the absence of a specific FDA safety determination, such suits can go forward.”

(This article is written as part of a series on pharmaceutical litigation and is sponsored by Robert Kwok & Associated, LLP)

Filed under: 2007, Bextra, Birth Defects, Bush, Celexa, Colacicco, Elidel, FDA, Glaxo, Kwok, McNellis, Novartis, Paxil, Perry, Preemption, SSRIs, Troy, Vioxx

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    Originally posted on The Bitter Pill:Kickstarter is a website for artists to use to raise money and complete awesome projects. The best thing to come to the informed consent movement since Thomas Szasz could just be the new, upcoming film by Dan Jenski, “ADDicted” which basically gives Ritalin, Adderall, Concerta and the like a…
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    Originally posted on The Bitter Pill:In the studies submitted to the FDA for approving Zoloft (a drug that has killed numerous families, babies, mothers, children), the drug maker covered up the fact that Zoloft failed to outperform placebo, according to a new consumer fraud lawsuit filed by the firms Baum, Hedlund Aristei & Goldman…
  • Antidepressants Again Linked to Preterm Birth & Seizures
    In what was more than likely originally an attempt to prove that depression causes birth complications, researchers from Yale, Tufts, et al found in two new studies that antidepressants increase the risk of preterm birth and seizures. Read more at this link on the newly redesigned UNITE website.
  • Who Could Do This On Purpose
    Read this blog to find out
  • Canadian Regulation on Fetal Exposure to Psychotropic Drugs – Public Input Needed
    Canadian Regulation on Fetal Exposure to Psychotropic Drugs – Public Input Needed (Cross-Posted on The Bitter Pill blog) Amery and Christiane Schultz have been asked to provide input on proposed recommendations regarding psychotropic drugs in pregnancy in Canada. Amery & Christiane are hard-working activists affiliated with UNITE and MADNAP. Please send […]

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